Bio

Academic Appointments


Administrative Appointments


  • Professor of Medicine (Research), Stanford University (2003 - Present)
  • Associate Professor of Medicine (Research), Stanford University (1997 - 2003)

Honors & Awards


  • Co-Founder, Co-Director, Stanford WSDM Center (Stanford Center for Health Research on Women & Sex Differences) (currrent)
  • Fellow, American Heart Association (2001-present)
  • Fellow, American Heart Association Council of Arteriosclerosis, Thrombosis and Vascular Biology (1989-present)
  • Fellow, American College of Sports Medicine (ASCM) (1984-present)

Professional Education


  • Ph.D., Stanford University, Physiology (1982)
  • B.A., University of Pennsylvania, Biology (1974)

Research & Scholarship

Current Research and Scholarly Interests


Marcia Stefanick, Ph.D a Professor of Medicine at the Stanford Prevention Research Center, (SPRC) and Professor of Obstetrics and Gynecology, Stanford University School of Medicine.
Dr. Stefanicks research focuses on chronic disease prevention (particularly, heart disease, breast cancer, osteoporosis, and dementia) in both women and men. Her work on the effects of menopausal hormones on cardiovascular and other health outcomes in mostly healthy postmenopausal women (in the Womens Health Initiative, WHI), in women with established heart disease, (the Heart and Estrogen-progesterone Replacement Study, HERS), and in peri-menopausal and early post-menopausal women (the Postmenopausal Estrogen and Progesterone Interventions, PEPI) trials has been widely disseminated both nationally and internationally. She was also the principal investigator of two large diet trials focusing on the role of a low-fat eating pattern (including increased vegetables & fruits) on preventing breast cancer (WHI) and recurrence (Womens Healthy Eating and Living, WHEL, trial) and she conducted several medium-sized diet, exercise, and weight control trials focused on heart disease risk and body composition that have influenced national guidelines. [She is currently writing a proposal for a large national trial of physical activity in older women with cardiovascular outcomes, not just risk factors.] Her current passion is the study of Sex (and Gender) Differences in Human Physiology and Disease, the title of a course she teaches in Stanfords Human Biology program, in addition to a course entitled: Current Topics and Controversies in Womens Health. Dr. Stefanick also plays major leadership roles in Stanfords Cardiovascular Institutes Womens Heart Health Program and Stanford Cancer Institutes Cancer Prevention and Control Program.
Dr. Stefanick obtained her B.A. in biology from the University of Pennsylvania, Philadelphia, PA (1974), then pursued her interest in hormone and sex difference research at the Oregon Regional Primate Research Center, after which she obtained her PhD in Physiology at Stanford University, focusing on reproductive physiology and neuroendocrinology with exercise physiology as a secondary focus. Her commitment to human research directed her to a post-doctoral fellowship in Cardiovascular Disease Prevention at SPRC, which has been her academic home for nearly 30 years.

Clinical Trials


  • Sex Differences in Coronary Pathophysiology Recruiting

    This is a research study evaluating possible causes of chest pain (or an anginal equivalent, such as fatigue resulting in a decrease in exercise tolerance, shortness of breath, or back, shoulder, neck, or jaw pain) in people with no evidence of significant coronary artery disease on their coronary angiogram (pictures of the blood vessels in the heart). The purpose of the research study is to determine if there is diffuse atherosclerosis (plaque) not appreciated by angiography, or if the coronary endothelium (lining of the blood vessels in the heart) and/or microcirculation (small vessels in the heart that are not easily seen with an angiogram) are not functioning properly in those who have chest pain (or an anginal equivalent), but normal coronary arteries on angiography. Specifically, we are interested if these findings are more common in women than men.

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Teaching

2013-14 Courses


Postdoctoral Advisees


Graduate and Fellowship Programs


Publications

Journal Articles


  • Age at menopause, reproductive history, and venous thromboembolism risk among postmenopausal women: the Women's Health Initiative hormone therapy clinical trials. Menopause (New York, N.Y.) Canonico, M., Plu-Bureau, G., O'Sullivan, M. J., Stefanick, M. L., Cochrane, B., Scarabin, P., Manson, J. E. 2014; 21 (3): 214-220

    Abstract

    OBJECTIVE: This study aims to investigate venous thromboembolism (VTE) risk in relation to age at menopause, age at menarche, parity, bilateral oophorectomy, and time since menopause, as well as any interaction with randomized hormone therapy (HT) assignment, among postmenopausal women. METHODS: Using pooled data from the Women's Health Initiative HT clinical trials including 27,035 postmenopausal women aged 50 to 79 years who had no history of VTE, we assessed the risk of VTE in relation to age at menopause, age at menarche, parity, bilateral oophorectomy, and time since menopause by Cox proportional hazards models. Linear trends, quadratic relationships, and interactions of reproductive life characteristics with HT on VTE risk were systematically tested. RESULTS: During follow-up, 426 women reported a first VTE, including 294 non-procedure-related events. No apparent interaction of reproductive life characteristics with HT assignment on VTE risk was detected, and there was not a significant association between VTE and age at menarche, age at menopause, parity, oophorectomy, or time since menopause. However, analyses restricted to non-procedure-related VTE showed a U-shaped relationship between age at menopause and thrombotic risk that persisted after multivariable analysis (P < 0.01). Compared with women aged 40 to 49 years at menopause, those who had early menopause (age <40 y) or late menopause (age >55 y) had a significantly increased VTE risk (hazard ratio [95% CI]: 1.8 [1.2-2.7] and 1.5 [1.0-2.4], respectively). CONCLUSIONS: Reproductive life characteristics have little association with VTE and do not seem to influence the effect of HT on thrombotic risk among postmenopausal women. Nevertheless, early and late onset of menopause might be newly identified risk factors for non-procedure-related VTE.

    View details for DOI 10.1097/GME.0b013e31829752e0

    View details for PubMedID 23760439

  • Women's Health Initiative clinical trials: interaction of calcium and vitamin D with hormone therapy. Menopause (New York, N.Y.) Robbins, J. A., Aragaki, A., Crandall, C. J., Manson, J. E., Carbone, L., Jackson, R., Lewis, C. E., Johnson, K. C., Sarto, G., Stefanick, M. L., Wactawski-Wende, J. 2014; 21 (2): 116-123

    Abstract

    This study aims to test the added value of calcium and vitamin D (CaD) in fracture prevention among women taking postmenopausal hormone therapy (HT).This is a prospective, partial-factorial, randomized, controlled, double-blind trial among Women's Health Initiative postmenopausal participants aged 50 to 79 years at 40 centers in the United States with a mean follow-up of 7.2 years. A total of 27,347 women were randomized to HT (0.625 mg of conjugated estrogens alone, or 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily), and 36,282 women were randomized to 1,000 mg of elemental calcium (carbonate) plus 400 IU of vitamin D3 daily, each compared with placebo. A total of 16,089 women participated in both arms. The predefined outcomes were adjudicated hip fractures and measured bone mineral density.Interaction between HT and CaD on hip fracture (P interaction = 0.01) was shown. The effect of CaD was stronger among women assigned to HT (hazard ratio [HR], 0.59; 95% CI, 0.38-0.93) than among women assigned to placebo (HR, 1.20; 95% CI, 0.85-1.69). The effect of HT on hip fracture was stronger among women assigned to active CaD (HR, 0.43; 95% CI, 0.28-0.66) than among women assigned to placebo (HR, 0.87; 95% CI, 0.60-1.26). CaD supplementation enhanced the antifracture effect of HT at all levels of personal calcium intake. There was no interaction between HT and CaD on change in hip or spine bone mineral density.Postmenopausal women at normal risk for hip fracture who are on CaD supplementation experience significantly reduced incident hip fractures beyond HT alone at all levels of personal baseline total calcium intake.

    View details for DOI 10.1097/GME.0b013e3182963901

    View details for PubMedID 23799356

  • Change in physical activity after a diabetes diagnosis: opportunity for intervention. Medicine and science in sports and exercise Schneider, K. L., Andrews, C., Hovey, K. M., Seguin, R. A., Manini, T., LaMonte, M. J., Margolis, K. L., Waring, M. E., Ning, Y., Sims, S., Ma, Y., Ockene, J., Stefanick, M. L., Pagoto, S. L. 2014; 46 (1): 84-91

    Abstract

    Moderate intensity physical activity is recommended for individuals with diabetes to control glucose and prevent diabetes-related complications. The extent to which a diabetes diagnosis motivates patients to increase physical activity is unclear. This study used data from the Women's Health Initiative Observational Study (baseline data collected from 1993-1998) to examine change in physical activity and sedentary behavior in women who reported a diabetes diagnosis compared to women who did not report diabetes over 7 years of follow-up (up to 2005).Participants (n=84,300) were post-menopausal women who did not report diabetes at baseline [mean age=63.49; standard deviation (SD)=7.34; mean BMI=26.98 kg/m; SD=5.67]. Linear mixed model analyses were conducted adjusting for study year, age, race/ethnicity, BMI, education, family history of diabetes, physical functioning, pain, energy/fatigue, social functioning, depression, number of chronic diseases and vigorous exercise at age 18. Analyses were completed in August 2012.Participants who reported a diabetes diagnosis during follow-up were more likely to report increasing their total physical activity (p=0.002), walking (p<0.001) and number of physical activity episodes (p<0.001) compared to participants who did not report a diabetes diagnosis. On average, participants reporting a diabetes diagnosis reported increasing their total physical activity by 0.49 MET-hours/week, their walking by 0.033 MET-hours/week and their number of physical activity episodes by 0.19 MET-hours/week. No differences in reported sedentary behavior change were observed (p=0.48).A diabetes diagnosis may prompt patients to increase physical activity. Healthcare professionals should consider how best to capitalize on this opportunity to encourage increased physical activity and maintenance.

    View details for DOI 10.1249/MSS.0b013e3182a33010

    View details for PubMedID 23860414

  • Mortality risk in former smokers with breast cancer: Pack-years vs. smoking status. International journal of cancer. Journal international du cancer Saquib, N., Stefanick, M. L., Natarajan, L., Pierce, J. P. 2013; 133 (10): 2493-2497

    Abstract

    It is unclear why successful quitting at time of breast cancer diagnosis should remove risk from a significant lifetime of smoking. Studies concluding this may be biased by how smoking is measured in many epidemiological cohorts. In the late 1990s, a randomized trial of diet and breast cancer outcomes enrolled early-stage female breast cancer survivors diagnosed within the previous 4 years. Smoking history and key covariate measures were available at study entry for 2,953 participants. Participants were followed for an average of 7.3 years (96% response rate). There were 10.1% deaths (83% from breast cancer). At enrollment, 55.2% were never smokers, 41.2% former smokers and 4.6% current smokers. Using current smoking status in a Cox regression, there was no increased risk for former smokers for either all-cause mortality [hazard ratio (HR) = 1.11; 95% confidence interval (CI) = 0.87-1.41; p-value = 0.42) or breast cancer mortality. However, when we categorized on extensive lifetime exposure, former smokers with 20+ pack-years of smoking (25.8%) had a significantly higher risk of both all-cause (HR = 1.77; 95% CI = 1.17-2.48; p-value = 0.0007) and breast cancer-specific mortality (HR = 1.62; 95% CI = 1.11-2.37; p-value = 0.01). Lifetime smoking exposure, not current status, should be used to assess mortality risk among former smokers.

    View details for DOI 10.1002/ijc.28241

    View details for PubMedID 23649774

  • Calcium Plus Vitamin D Supplementation and Joint Symptoms in Postmenopausal Women in the Women's Health Initiative Randomized Trial. Journal of the Academy of Nutrition and Dietetics Chlebowski, R. T., Pettinger, M., Johnson, K. C., Wallace, R., Womack, C., Mossavar-Rahmani, Y., Stefanick, M., Wactawski-Wende, J., Carbone, L., Lu, B., Eaton, C., Walitt, B., Kooperberg, C. L. 2013; 113 (10): 1302-1310

    Abstract

    Low vitamin D intake and levels have been associated with increased joint symptoms in some observational studies but the findings are mixed and evidence from randomized trials sparse.To evaluate the influence of supplemental calcium and vitamin D on joint symptoms in the Women's Health Initiative randomized, placebo-controlled, clinical trial.In post hoc analyses, the results of the Women's Health Initiative randomized clinical trial in which 36,282 postmenopausal women were randomized to receive calcium carbonate (1,000 mg as elemental calcium) with vitamin D-3 (400 IU) daily or placebo were examined in the 6% subgroup of 1,911 participants, oversampled for minorities, who had serial joint symptom assessment. Qualitative information on joint pain and joint swelling was collected by questionnaire before entry and 2 years after randomization. Logistic regression models were used to compare the occurrence and severity of joint symptoms across randomization groups.At baseline, total calcium and vitamin D intakes from diet and supplements were similar in the two randomization groups. In addition, both joint pain (reported by 73%) and joint swelling (reported by 34%) were commonly reported and comparable in the supplement and placebo groups. Two years after randomization, no statistically significant differences between supplement and placebo groups were seen for joint pain frequency (74.6% compared with 75.1% [P=0.79] for supplement and placebo groups, respectively) or joint swelling frequency (34.6% compared with 32.4% [P=0.29], respectively) or in severity scores for either outcome. Subgroup analyses suggested study participants also using nonprotocol calcium supplements at study entry may have less joint pain with supplement group randomization (interaction P=0.02).Joint symptoms are relatively common in postmenopausal women. However, daily supplementation with 1,000 mg calcium carbonate and 400 IU vitamin D-3 in a randomized, placebo-controlled clinical trial setting did not reduce the self-reported frequency or severity of joint symptoms.

    View details for DOI 10.1016/j.jand.2013.06.007

    View details for PubMedID 23954097

  • Abdominal Myosteatosis Is Independently Associated with Hyperinsulinemia and Insulin Resistance Among Older Men Without Diabetes OBESITY Miljkovic, I., Cauley, J. A., Wang, P. Y., Holton, K. F., Lee, C. G., Sheu, Y., Barrett-Connor, E., Hoffman, A. R., Lewis, C. B., Orwoll, E. S., Stefanick, M. L., Strotmeyer, E. S., Marshall, L. M. 2013; 21 (10): 2118-2125

    Abstract

    OBJECTIVE: Skeletal muscle adipose tissue (AT) infiltration (myosteatosis) increases with aging and may contribute to the development of Type 2 diabetes mellitus (T2DM). It remains unclear if myosteatosis is associated to glucose and insulin homeostasis independent of total and central adiposity. DESIGN AND METHODS: The association between intermuscular AT (IMAT) in the abdominal skeletal muscles (total, paraspinal, and psoas) and fasting serum glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) in 393 nondiabetic Caucasian men aged 65+ was evaluated. Abdominal IMAT, visceral AT (VAT), and subcutaneous AT (SAT) (cm(3) ) were measured by quantitative computed tomography at the L4-L5 intervertebral space. RESULTS: In age, study site, height, and muscle volume adjusted regression analyses, total abdominal and psoas (but not paraspinal) IMAT were positively associated with glucose, insulin, and HOMA-IR (all P < 0.003). The associations between total abdominal and psoas IMAT and insulin and HOMA-IR remained significant after further adjusting for lifestyle factors, as well as duel-energy x-ray absorptiometry (DXA) measured total body fat, VAT, or SAT in separate models (all P < 0.009). CONCLUSIONS: A previously unreported, independent association between abdominal myosteatosis and hyperinsulinemia and insulin resistance among older Caucasian men was indicated. These associations may be specific for particular abdominal muscle depots, illustrating the potential importance of separately studying specific muscle groups.

    View details for DOI 10.1002/oby.20346

    View details for Web of Science ID 000325427300021

    View details for PubMedID 23408772

  • African American race but not genome-wide ancestry is negatively associated with atrial fibrillation among postmenopausal women in the Women's Health Initiative. American heart journal Perez, M. V., Hoffmann, T. J., Tang, H., Thornton, T., Stefanick, M. L., Larson, J. C., Kooperberg, C., Reiner, A. P., Caan, B., Iribarren, C., Risch, N. 2013; 166 (3): 566-572 e1

    Abstract

    Atrial fibrillation (AF) is the most common arrhythmia in women and is associated with higher rates of stroke and death. Rates of AF are lower in African American subjects compared with European Americans, suggesting European ancestry could contribute to AF risk.The Women's Health Initiative (WHI) Observational Study (OS) followed up 93,676 women since the mid 1990s for various cardiovascular outcomes including AF. Multivariate Cox hazard regression analysis was used to measure the association between African American race and incident AF. A total of 8,119 African American women from the WHI randomized clinical trials and OS were genotyped on the Affymetrix Human SNP Array 6.0. Genome-wide ancestry and previously reported single nucleotide polymorphisms associated with AF in European cohorts were tested for association with AF using multivariate logistic regression analyses.Self-reported African American race was associated with lower rates of AF (hazard ratio 0.43, 95% CI 0.32-0.60) in the OS, independent of demographic and clinical risk factors. In the genotyped cohort, there were 558 women with AF. By contrast, genome-wide European ancestry was not associated with AF. None of the single nucleotide polymorphisms previously associated with AF in European populations, including rs2200733, were associated with AF in the WHI African American cohort.African American race is significantly and inversely correlated with AF in postmenopausal women. The etiology of this association remains unclear and may be related to unidentified environmental differences. Larger studies are necessary to identify genetic determinants of AF in African Americans.

    View details for DOI 10.1016/j.ahj.2013.05.024

    View details for PubMedID 24016508

  • Relationships among changes in C-reactive protein and cardiovascular disease risk factors with lifestyle interventions NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES Young, D., CAMHI, S., Wu, T., Hagberg, J., Stefanick, M. 2013; 23 (9): 857-863

    Abstract

    BACKGROUND AND AIMS: Inflammation plays a role in the development of cardiovascular disease (CVD). Elevated levels of the inflammatory marker, C-reactive protein (CRP), are cross-sectionally associated with traditional CVD risk factors and are being considered as an emerging CVD risk factor. In a secondary data analysis, we examined changes in CRP and several CVD risk factors after one-year diet and physical activity interventions to assess whether CRP changed concurrently with other risk factors, or was independent of the traditional risk factors. METHODS AND RESULTS: Data were analyzed from 143 men and 133 women with dyslipidemia who were randomized to one-year interventions of low-fat diet only, physical activity only, diet plus physical activity, or control. Plasma high-sensitivity CRP, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides (TG), fasting and 2-hr blood glucose and insulin, blood pressure (BP), and waist circumference were obtained at baseline and follow-up. Multiple linear regression models were used to predict CRP change based on other risk factor changes, controlling for age, race, alcohol intake, and hormone replacement therapy. Treatment groups were combined for analysis. Baseline mean (SD) CRP levels were 1.3 ± 1.3 (men) and 1.9 ± 1.8 mg/L (women), with mean changes of -0.11 ± 1.3 and -0.17 ± 1.5 mg/L, respectively. Plasma CRP change was negatively associated with TG change in men (p = 0.003) and women (p = 0.05), positively associated with change in systolic BP in men (p = 0.01), but was not associated with changes in the other risk factors. CONCLUSION: Dietary and/or physical activity induced changes in CRP may be largely independent of traditional CVD risk factors in persons with dyslipidemia.

    View details for DOI 10.1016/j.numecd.2012.05.003

    View details for Web of Science ID 000324538200009

    View details for PubMedID 22831953

  • Low-Fat Diet and Skin Cancer Risk: The Women's Health Initiative Randomized Controlled Dietary Modification Trial CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Gamba, C. S., Stefanick, M. L., Shikany, J. M., Larson, J., Linos, E., Sims, S. T., Marshall, J., Van Horn, L., Zeitouni, N., Tang, J. Y. 2013; 22 (9): 1509-1519

    Abstract

    Background: Large cohort studies have reported no relationship between dietary fat and nonmelanoma skin cancer (NMSC), although a low-fat diet intervention reduced NMSC risk in a small clinical trial. In animal studies, skin tumor development has been reduced by low-fat diet. We evaluated the effect of a low-fat dietary pattern on NMSC and melanoma in the Women's Health Initiative Dietary Modification trial. Methods: Postmenopausal women aged 50 to 79 years (N=48,835) were randomly assigned to the low-fat dietary pattern intervention (N=19,541) or comparison group (N=29,294). The intervention goals included decreasing fat intake to ≤20% of calories, increasing vegetable and fruit intake, and increasing grain intake. Self-reported incident NMSC (N=4,907) and physician-adjudicated incident melanoma (N=279) were ascertained every 6 months. Results: Over 8.1 years of follow-up, the low-fat diet intervention did not affect overall incidence of NMSC (hazard ratio [HR] 0.98, 95% confidence interval [CI]: 0.92-1.04) or melanoma (HR 1.04, 95% CI: 0.82-1.32). In subgroup analyses of melanoma risk, baseline fat intake interacted significantly with group assignment (Pinteraction=0.006). Among women with higher baseline fat intake, the dietary intervention significantly increased risk (HR 1.48; 95% CI: 1.06-2.07), whereas, among women with lower baseline fat intake, the intervention tended to reduce melanoma risk (HR 0.72, 95% CI: 0.50-1.02). Conclusions: In this large randomized trial, a low-fat dietary pattern did not affect overall incidence of NMSC or melanoma. Impact: A low-fat diet does not reduce incidence of NMSC, but an interaction between baseline fat intake and dietary intervention on melanoma risk warrants further investigation.

    View details for DOI 10.1158/1055-9965.EPI-13-0341

    View details for Web of Science ID 000324674500004

    View details for PubMedID 23697610

  • Changes in physical activity and body composition in postmenopausal women over time. Medicine and science in sports and exercise Sims, S. T., Kubo, J., Desai, M., Bea, J., Beasley, J. M., Manson, J. E., Allison, M., Seguin, R. A., Chen, Z., Michael, Y. L., Sullivan, S. D., Beresford, S., Stefanick, M. L. 2013; 45 (8): 1486-1492

    Abstract

    PURPOSE: Higher physical activity (PA) has been associated with greater attenuation of body-fat gain and preservation of lean mass across the lifespan. These analyses aimed to determine relationships of change in PA to changes in fat and lean body mass in a longitudinal prospective study of postmenopausal women. METHODS: Among 11,491 women enrolled at three Women's Health Initiative (WHI) clinical centers were selected to undergo dual-energy x-ray absorptiometry (DXA), 8,352 had baseline body composition measurements, with at least one repeated measure at yr 1, 3, and 6. PA data were obtained by self-report at baseline, 3 and 6 yr of follow-up. Time-varying PA impact on change in lean and fat mass during the six-yr study period for age groups (50-59y, 60-69y, 70- 79y) was estimated using mixed effects linear regression. RESULTS: Baseline PA and body composition differed significantly among the three age groups. The association of change in fat mass from baseline and time-varying PA differed across the three age groups (p=0.0006). In women aged 50-59, gain in fat mass from baseline was attenuated with higher levels of physical activity. Women aged 70-79 lost fat mass at all PA levels. In contrast, change in lean mass from baseline and time-varying PA did not differ by age group (p=0.1935). CONCLUSIONS: The association between PA and change in fat mass varies by age group, with younger, but not older, women benefitting from higher levels of aerobic PA. Higher levels of aerobic activity are not associated with changes in lean mass, which tends to decrease in older women regardless of activity level. Greater attention to resistance training exercises may be needed to prevent lean mass loss as women age.

    View details for DOI 10.1249/MSS.0b013e31828af8bd

    View details for PubMedID 23439422

  • Risk factors for atrial fibrillation and their population burden in postmenopausal women: the Women's Health Initiative Observational Study. Heart Perez, M. V., Wang, P. J., Larson, J. C., Soliman, E. Z., Limacher, M., Rodriguez, B., Klein, L., Manson, J. E., Martin, L. W., Prineas, R., Connelly, S., Hlatky, M., Wassertheil-Smoller, S., Stefanick, M. L. 2013; 99 (16): 1173-1178

    Abstract

    OBJECTIVE: Atrial fibrillation (AF) is the most common arrhythmia in women. Large studies evaluating key AF risk factors in older women are lacking. We aimed to identify risk factors for AF in postmenopausal women and measure population burden of modifiable risk factors. DESIGN: Prospective observational study. SETTING: The Women's Health Initiative (WHI) Observational Study. PATIENTS: 93 676 postmenopausal women were followed for an average of 9.8 years for cardiovascular outcomes. After exclusion of women with prevalent AF or incomplete data, 8252 of the remaining 81 892 women developed incident AF. MAIN OUTCOME MEASURES: Incident AF was identified by WHI-ascertained hospitalisation records and diagnosis codes from Medicare claims. Multivariate Cox hazard regression analysis identified independent risk factors for incident AF. RESULTS: Age, hypertension, obesity, diabetes, myocardial infarction and heart failure were independently associated with incident AF. Hypertension and overweight status accounted for 28.3% and 12.1%, respectively, of the population attributable risk. Hispanic and African-American participants had lower rates of incident AF (HR 0.58, 95% CI 0.47 to 0.70 and HR 0.59, 95% CI 0.53 to 0.65, respectively) than Caucasians. CONCLUSIONS: Caucasian ethnicity, traditional cardiovascular risk factors and peripheral arterial disease were independently associated with higher rates of incident AF in postmenopausal women. Hypertension and overweight status accounted for a large proportion of population attributable risk. Measuring burden of modifiable AF risk factors in older women may help target interventions.

    View details for DOI 10.1136/heartjnl-2013-303798

    View details for PubMedID 23756655

  • Relationship of Sedentary Behavior and Physical Activity to Incident Cardiovascular Disease JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Chomistek, A. K., Manson, J. E., Stefanick, M. L., Lu, B., Sands-Lincoln, M., Going, S. B., Garcia, L., Allison, M. A., Sims, S. T., LaMonte, M. J., Johnson, K. C., Eaton, C. B. 2013; 61 (23): 2346-2354

    Abstract

    OBJECTIVES: The aim was to examine the independent and joint associations of sitting time and physical activity with risk of incident cardiovascular disease (CVD). BACKGROUND: Sedentary behavior is recognized as a distinct construct beyond lack of leisure-time physical activity, but limited data exists on the interrelationship between these two components of energy balance. METHODS: Participants in the prospective Women's Health Initiative Observational Study (N = 71,018), aged 50-79 and free of CVD at baseline (1993-1998), provided information on sedentary behavior, defined as hours of sitting per day, and usual physical activity at baseline and during follow-up through September 2010. First CVD (coronary heart disease or stroke) events were centrally adjudicated. RESULTS: Sitting ≥ 10 hours/day compared to ≤ 5 hours/day was associated with increased CVD risk (HR=1.18, 95% CI 1.09, 1.29) in multivariable models including physical activity. Low physical activity was also associated with higher CVD risk (P,trend <0.001). When women were cross-classified by sitting time and physical activity (P,interaction = 0.94), CVD risk was highest in inactive women (≤1.7 MET-hrs/week) who also reported ≥10 hrs/day of sitting. Results were similar for CHD and stroke when examined separately. Associations between prolonged sitting and risk of CVD were stronger in overweight versus normal weight women and women aged 70 years and older compared to younger women. CONCLUSIONS: Prolonged sitting time was associated with increased CVD risk, independent of leisure-time physical activity, in postmenopausal women without a history of CVD. A combination of low physical activity and prolonged sitting augments CVD risk.

    View details for DOI 10.1016/j.jacc.2013.03.031

    View details for Web of Science ID 000320601400007

  • Estrogen alone and joint symptoms in the Women's Health Initiative randomized trial MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Chlebowski, R. T., Cirillo, D. J., Eaton, C. B., Stefanick, M. L., Pettinger, M., Carbone, L. D., Johnson, K. C., Simon, M. S., Woods, N. F., Wactawski-Wende, J. 2013; 20 (6): 600-608
  • Sleep Duration, Insomnia, and Coronary Heart Disease Among Postmenopausal Women in the Women's Health Initiative. Journal of women's health (2002) Sands-Lincoln, M., Loucks, E. B., Lu, B., Carskadon, M. A., Sharkey, K., Stefanick, M. L., Ockene, J., Shah, N., Hairston, K. G., Robinson, J. G., Limacher, M., Hale, L., Eaton, C. B. 2013; 22 (6): 477-486

    Abstract

    Abstract Background: Long and short sleep duration are associated with increased risk for coronary heart disease (CHD) and cardiovascular disease (CVD); however, evidence is inconsistent. We sought to identify whether self-reported sleep duration and insomnia, based on a validated questionnaire, are associated with increased incident CHD and CVD among postmenopausal women. Methods: Women's Health Initiative Observational Study Participants (N=86,329; 50-79 years) who reported on sleep at baseline were followed for incident CVD events. Associations of sleep duration and insomnia with incident CHD and CVD were evaluated using Cox proportional hazards models over 10.3 years. Results: Women with high insomnia scores had elevated risk of CHD (38%) and CVD (27%) after adjustment for age and race, and in fully adjusted models (hazard ratio [HR]=1.19, 95% confidence interval [CI] 1.09-1.30; 1.11 95% CI 1.03-2.00). Shorter (?5 hours) and longer (?10 hours) sleep duration demonstrated significantly higher incident CHD (25%) and CVD (19%) in age- and race-adjusted models, but this was not significant in fully adjusted models. Formal tests for interaction indicated significant interactions between sleep duration and insomnia for risk of CHD (p<0.01) and CVD (p=0.02). Women with high insomnia scores and long sleep demonstrated the greatest risk of incident CHD compared to midrange sleep duration (HR=1.93, 95% CI 1.06-3.51) in fully adjusted models. Conclusions: Sleep duration and insomnia are associated with CHD and CVD risk, and may interact to cause almost double the risk of CHD and CVD. Additional research is needed to understand how sleep quality modifies the association between prolonged sleep and cardiovascular outcomes.

    View details for DOI 10.1089/jwh.2012.3918

    View details for PubMedID 23651054

  • Self-perceived physical health predicts cardiovascular disease incidence and death among postmenopausal women BMC PUBLIC HEALTH Saquib, N., Brunner, R., Kubo, J., Tindle, H., Kroenke, C., Desai, M., Daviglus, M. L., Allen, N., Martin, L. W., Robinson, J., Stefanick, M. L. 2013; 13
  • Estrogen plus progestin and breast cancer incidence and mortality in the Women's Health Initiative Observational Study. Journal of the National Cancer Institute Chlebowski, R. T., Manson, J. E., Anderson, G. L., Cauley, J. A., Aragaki, A. K., Stefanick, M. L., Lane, D. S., Johnson, K. C., Wactawski-Wende, J., Chen, C., Qi, L., Yasmeen, S., Newcomb, P. A., Prentice, R. L. 2013; 105 (8): 526-535

    Abstract

    In the Women's Health Initiative (WHI) randomized trial, estrogen plus progestin increased both breast cancer incidence and mortality. In contrast, most observational studies associate estrogen plus progestin with favorable prognosis breast cancers. To address differences, a cohort of WHI observational study participants with characteristics similar to the WHI clinical trial was studied.We identified 41 449 postmenopausal women with no prior hysterectomy and mammogram negative within 2 years who were either not hormone users (n = 25 328) or estrogen and progestin users (n = 16 121). Multivariable-adjusted Cox proportional hazard regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). All statistical tests were two-sided.After a mean of 11.3 (SD = 3.1) years, with 2236 breast cancers, incidence was higher in estrogen plus progestin users than in nonusers (0.60% vs 0.42%, annualized rate, respectively; HR = 1.55, 95% CI = 1.41 to 1.70, P < .001). Women initiating hormone therapy closer to menopause had higher breast cancer risk with linear diminishing influence as time from menopause increased (P < .001). Survival after breast cancer, measured from diagnosis, was similar in combined hormone therapy users and nonusers (HR = 1.03, 95% CI = 0.79 to 1.35). On a population basis, there were somewhat more deaths from breast cancer, measured from cohort entry (HR = 1.32, 95% CI = 0.90 to 1.93, P = .15), and more all-cause deaths after breast cancer (HR = 1.65, 95% CI = 1.29 to 2.12, P < .001) in estrogen plus progestin users than in nonusers.Consistent with WHI randomized trial findings, estrogen plus progestin use is associated with increased breast cancer incidence. Because prognosis after diagnosis on combined hormone therapy is similar to that of nonusers, increased breast cancer mortality can be expected.

    View details for DOI 10.1093/jnci/djt043

    View details for PubMedID 23543779

  • Aspirin is associated with lower melanoma risk among postmenopausal Caucasian women The Women's Health Initiative CANCER Gamba, C. A., Swetter, S. M., Stefanick, M. L., Kubo, J., Desai, M., Spaunhurst, K. M., Sinha, A. A., Asgari, M. M., Sturgeon, S., Tang, J. Y. 2013; 119 (8): 1562-1569

    Abstract

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with decreased risk of gastric, colorectal, and breast cancer. However, the impact of NSAIDs on the risk of melanoma has been inconsistent. The authors evaluated the association between NSAID use and cutaneous melanoma risk in the Women's Health Initiative (WHI) Observational Study (OS).At study entry, use of aspirin (acetylsalicylic acid [ASA]) and nonaspirin NSAIDs was assessed among 59,806 postmenopausal Caucasian women ages 50 to 79 years. Cox proportional hazards models were constructed after adjusting for participant skin type, sun exposure history, and medical indications for NSAID use among other confounders.During a median follow-up of 12 years, 548 incident melanomas were confirmed by medical review. Women who used ASA had a 21% lower risk of melanoma (hazard ratio, 0.79; 95% confidence interval, 0.63-0.98) relative to nonusers. Increased duration of ASA use (<1 year, 1-4 years, and ? 5 years) was associated with an 11% lower risk of melanoma for each categorical increase (Ptrend = .01), and women with ? 5 years of use had a 30% lower melanoma risk (hazard ratio, 0.70; 95% confidence interval, 0.55-0.94). In contrast, use of non-ASA NSAIDs and acetaminophen were not associated with melanoma risk.Postmenopausal women who used ASA had a significantly lower risk of melanoma, and longer duration of ASA use was associated with greater protection. Although this study was limited by the observational design and self-report of NSAID use, the findings suggest that ASA may have a chemopreventive effect against the development of melanoma and warrant further clinical investigation.

    View details for DOI 10.1002/cncr.27817

    View details for Web of Science ID 000317618700016

    View details for PubMedID 23483536

  • Physical Activity Assessment: Biomarkers and Self-Report of Activity-Related Energy Expenditure in the WHI AMERICAN JOURNAL OF EPIDEMIOLOGY Neuhouser, M. L., Di, C., Tinker, L. F., Thomson, C., Sternfeld, B., Mossavar-Rahmani, Y., Stefanick, M. L., Sims, S., Curb, J. D., LaMonte, M., Seguin, R., Johnson, K. C., Prentice, R. L. 2013; 177 (6): 576-585

    Abstract

    We used a biomarker of activity-related energy expenditure (AREE) to assess measurement properties of self-reported physical activity and to determine the usefulness of AREE regression calibration equations in the Women's Health Initiative. Biomarker AREE, calculated as the total energy expenditure from doubly labeled water minus the resting energy expenditure from indirect calorimetry, was assessed in 450 Women's Health Initiative participants (2007-2009). Self-reported AREE was obtained from the Arizona Activity Frequency Questionnaire (AAFQ), the 7-Day Physical Activity Recall (PAR), and the Women's Health Initiative Personal Habits Questionnaire (PHQ). Eighty-eight participants repeated the protocol 6 months later. Reporting error, measured as log(self-report AREE) minus log(biomarker AREE), was regressed on participant characteristics for each instrument. Body mass index was associated with underreporting on the AAFQ and PHQ but overreporting on PAR. Blacks and Hispanics underreported physical activity levels on the AAFQ and PAR, respectively. Underreporting decreased with age for the PAR and PHQ. Regressing logbiomarker AREE on logself-reported AREE revealed that self-report alone explained minimal biomarker variance (R(2) = 7.6, 4.8, and 3.4 for AAFQ, PAR, and PHQ, respectively). R(2) increased to 25.2, 21.5, and 21.8, respectively, when participant characteristics were included. Six-month repeatability data adjusted for temporal biomarker variation, improving R(2) to 79.4, 67.8, and 68.7 for AAFQ, PAR, and PHQ, respectively. Calibration equations "recover" substantial variation in average AREE and valuably enhance AREE self-assessment.

    View details for DOI 10.1093/aje/kws269

    View details for Web of Science ID 000316374500013

    View details for PubMedID 23436896

  • Coronary heart disease events in the Women's Health Initiative hormone trials: effect modification by metabolic syndrome: A nested case-control study within the Women's Health Initiative randomized clinical trials MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Wild, R. A., Wu, C., Curb, J. D., Martin, L. W., Phillips, L., Stefanick, M., Trevisan, M., Manson, J. E. 2013; 20 (3): 254-260

    Abstract

    Our objective was to determine whether metabolic syndrome (MetS) or its components modified the effect of hormone therapy (HT) on the risk of coronary heart disease (CHD) events in the Women's Health Initiative clinical trials.We performed a nested case-control study of incident CHD events during the first 4 years of follow-up in the Women's Health Initiative HT trials (estrogen plus progestin therapy [EPT] and estrogen therapy [ET]). There were 359 incident cases of CHD during follow-up. After the exclusion of women with cardiovascular disease (n = 90), diabetes, or hypertension at baseline (n = 103), 166 CHD cases were matched to 524 controls on age, randomization date, and hysterectomy status. MetS classification required at least three of five Adult Treatment Panel III criteria. Analyses by ? and t tests for heterogeneity and logistic regression were performed. Postmenopausal women (n = 27,347) aged 50 to 79 years from 40 US clinical centers participated. Daily conjugated equine estrogens (0.625 mg) and medroxyprogesterone acetate (2.5 mg; EPT) or conjugated equine estrogens (0.625 mg; ET) were compared with placebo. The main outcome measure was the odds for CHD with HT use versus placebo by MetS status.MetS modified the risk of CHD events with HT. In the pooled analysis, risk was increased with HT versus placebo in women with MetS (odds ratio, 2.26; 95% CI, 1.26-4.07), whereas women without MetS were not found to have an increased risk for a CHD event with HT (odds ratio, 0.97; 95% CI, 0.58-1.61; P for interaction = 0.03). Results of the EPT and ET trials, when examined separately, were similar. The constellation of MetS variables was more predictive of risk from HT than MetS components assessed individually. When women with diabetes or hypertension were included in the analysis, statistically significant effect modification was not detected.MetS at baseline in women without prior cardiovascular disease, diabetes, or hypertension at baseline identifies women who are more likely to have had adverse coronary outcomes on HT. CHD risk stratification is recommended before initiating HT. The basis for the greater risk of CHD events with HT among women with MetS requires further study.

    View details for DOI 10.1097/gme.0b013e31826f80e0

    View details for Web of Science ID 000315603200006

    View details for PubMedID 23435021

  • Geriatric Syndromes and Incident Disability in Older Women: Results from the Women's Health Initiative Observational Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Rosso, A. L., Eaton, C. B., Wallace, R., Gold, R., Stefanick, M. L., Ockene, J. K., Curb, J. D., Michael, Y. L. 2013; 61 (3): 371-379

    Abstract

    To determine how the number of geriatric syndromes is associated with incident disability in community-based populations of older adults.Longitudinal analysis from the Women's Health Initiative Observational Study (WHI-OS).Community.Twenty-nine thousand five hundred forty-four women aged 65 and older enrolled in the WHI-OS and free of disability in activities of daily living (ADLs) at baseline.Geriatric syndromes (high depressive symptoms, dizziness, falls, hearing or visual impairment, osteoporosis, polypharmacy, syncope, sleep disturbance, and urinary incontinence) were self-reported at baseline and 3-year follow-up. Disability was defined as dependence in any ADL and was assessed at baseline and follow-up. Chronic diseases were measured according to a modified Charlson Index.Geriatric syndromes were common in this population of women; 76.3% had at least one syndrome at baseline. Greater number of geriatric syndromes at baseline was significantly associated with greater risk of incident ADL disability at follow-up (P ? .001). Adjusted risk ratios were 1.21 (95% confidence interval (CI) = 0.78-1.87) for a single syndrome and 6.64 (95% CI = 4.15-10.62) for five or more syndromes compared with no syndromes. These results were only slightly attenuated after adjustment for number of chronic diseases or pain.Geriatric syndromes are significantly associated with onset of disability in older women; this association is not simply a result of chronic disease or pain. A better understanding of how these conditions contribute to disablement is needed. Geriatric syndrome assessment should be considered along with chronic disease management in the prevention of disability in older women.

    View details for DOI 10.1111/jgs.12147

    View details for Web of Science ID 000316334900008

    View details for PubMedID 23452034

  • Self-Reported Snoring and Risk of Cardiovascular Disease Among Postmenopausal Women (from the Women's Health Initiative) AMERICAN JOURNAL OF CARDIOLOGY Sands, M., Loucks, E. B., Lu, B., Carskadon, M. A., Sharkey, K., Stefanick, M., Ockene, J., Shah, N., Hairston, K. G., Robinson, J., Limacher, M., Hale, L., Eaton, C. B. 2013; 111 (4): 540-546

    Abstract

    Habitual snoring may be associated with cardiovascular disease (CVD); however, limited evidence exists among women. We investigated whether frequent snoring is a predictor of coronary heart disease (CHD) and stroke among 42,244 postmenopausal women participating in the Women's Health Initiative Observational Study. Participants provided self-reported information regarding snoring habits at baseline (1993 to 1998) and were followed up for outcomes through August 2009. Physician adjudicators confirmed CHD (defined as myocardial infarction, CHD death, revascularization procedures, or hospitalized angina) and ischemic stroke. Cox proportional hazards models were used to evaluate whether snoring frequency is a significant predictor of the adjudicated outcomes. We observed 2,401 incident cases of CHD during 437,899 person-years of follow-up. After adjusting for age and race, frequent snoring was associated with incident CHD (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.39 to 1.70) and stroke (HR 1.41, 95% CI 1.19 to 1.66), and all CVD (HR 1.46, 95% CI 1.34 to 1.60). In fully adjusted models that included CVD risk factors such as obesity, hypertension, and diabetes, frequent snoring was associated with a more modest increase in incident CHD (HR 1.14, 95% CI 1.01 to 1.28), stroke (HR 1.19, 95% CI 1.02 to 1.40), and CVD (HR 1.12, 95% CI 1.01 to 1.24). In conclusion, snoring is associated with a modest increased risk of incident CHD, stroke, and CVD after adjustment for CVD risk factors. Additional studies are needed to elucidate the mechanisms by which snoring might be associated with CVD risk factors and outcomes.

    View details for DOI 10.1016/j.amjcard.2012.10.039

    View details for Web of Science ID 000315322800014

    View details for PubMedID 23219175

  • Body mass index, physical activity, and survival after endometrial cancer diagnosis: Results from the Women's Health Initiative GYNECOLOGIC ONCOLOGY Arem, H., Chlebowski, R., Stefanick, M. L., Anderson, G., Wactawski-Wende, J., Sims, S., Gunter, M. J., Irwin, M. L. 2013; 128 (2): 181-186

    Abstract

    While low physical activity and high body mass index (BMI) have been associated with higher endometrial cancer incidence, no previous studies have evaluated the association between physical activity and survival after endometrial cancer diagnosis, and studies on BMI and survival have not been performed in a prospective cohort.We examined pre-diagnosis BMI and moderate- to vigorous-intensity physical activity in relation to overall and disease-specific survival among 983 postmenopausal women who were diagnosed with endometrial cancer in the Women's Health Initiative Observational Study and Clinical Trials.Over a median 5.2 (max 14.1) years from diagnosis to death or end of follow-up, 163 total deaths were observed, 66 of which were due to endometrial cancer. We observed a higher all-cause mortality hazard ratio (HR) = 1.85 (95% CI 1.19-2.88) comparing women with a BMI ? 35 kg/m(2) to women with BMI< 25 kg/m(2). For endometrial cancer-specific mortality the HR = 2.23 (95% CI 1.09-4.54) comparing extreme BMI categories. To examine histologic subtypes we analyzed type I endometrial tumors separately and found an HR = 1.20 (95% CI 1.07-1.35) associated with all-cause mortality for each 5-unit change in BMI. Moderate- to vigorous-intensity physical activity was not associated with all-cause or endometrial cancer-specific mortality.Pre-diagnosis BMI, but not physical activity, was associated with survival among women with endometrial cancer. Future studies should investigate mechanisms and timing of BMI onset to better understand the burden of disease attributable to BMI.

    View details for DOI 10.1016/j.ygyno.2012.10.029

    View details for Web of Science ID 000314445300007

    View details for PubMedID 23127972

  • Self-perceived physical health predicts cardiovascular disease incidence and death among postmenopausal women. BMC public health Saquib, N., Brunner, R., Kubo, J., Tindle, H., Kroenke, C., Desai, M., Daviglus, M. L., Allen, N., Martin, L. W., Robinson, J., Stefanick, M. L. 2013; 13 (1): 468

    Abstract

    BACKGROUND: Physical and Mental Component Summary (PCS, MCS, respectively) scales of SF- 36 health-related-quality-of-life have been associated with all-cause and cardiovascular disease (CVD) mortality. Their relationships with CVD incidence are unclear. This study purpose was to test whether PCS and/or MCS were associated with CVD incidence and death. METHODS: Postmenopausal women (aged 50--79 years) in control groups of the Women's Health Initiative clinical trials (n = 20,308) completed the SF-36 and standardized questionnaires at trial entry. Health outcomes, assessed semi-annually, were verified with medical records. Cox regressions assessed time to selected outcomes during the trial phase (1993--2005). RESULTS: A total of 1075 incident CVD events, 204 CVD-specific deaths, and 1043 total deaths occurred during the trial phase. Women with low versus high baseline PCS scores had less favorable health profiles at baseline. In multivariable models adjusting for baseline confounders, participants in the lowest PCS quintile (reference = highest quintile) exhibited 1.8 (95%CI: 1.4, 2.3), 4.7 (95%CI: 2.3, 9.4), and 2.1 (95%CI: 1.7, 2.7) times greater risk of CVD incidence, CVD-specific death, and total mortality, respectively, by trial end; whereas, MCS was not significantly associated with CVD incidence or death. CONCLUSION: Physical health, assessed by self-report of physical functioning, is a strong predictor of CVD incidence and death in postmenopausal women; similar self-assessment of mental health is not. PCS should be evaluated as a screening tool to identify older women at high risk for CVD development and death.

    View details for PubMedID 23672763

  • Estrogen alone and joint symptoms in the Women's Health Initiative randomized trial. Menopause (New York, N.Y.) Chlebowski, R. T., Cirillo, D. J., Eaton, C. B., Stefanick, M. L., Pettinger, M., Carbone, L. D., Johnson, K. C., Simon, M. S., Woods, N. F., Wactawski-Wende, J. 2013; 20 (6): 600-608

    Abstract

    OBJECTIVE: Although joint symptoms are commonly reported after menopause, observational studies examining exogenous estrogen's influence on joint symptoms provide mixed results. Against this background, estrogen-alone effects on joint symptoms were examined in post hoc analyses in the Women's Health Initiative randomized, placebo-controlled, clinical trial. METHODS: A total of 10,739 postmenopausal women who have had a hysterectomy were randomized to receive daily oral conjugated equine estrogens (0.625 mg/d) or a matching placebo. The frequency and severity of joint pain and joint swelling were assessed by questionnaire in all participants at entry and on year 1, and in a 9.9% random subsample (n = 1,062) after years 3 and 6. Logistic regression models were used to compare the frequency and severity of symptoms by randomization group. Sensitivity analyses evaluated adherence influence on symptoms. RESULTS: At baseline, joint pain and joint swelling were closely comparable in the randomization groups (about 77% with joint pain and 40% with joint swelling). After 1 year, joint pain frequency was significantly lower in the estrogen-alone group compared with the placebo group (76.3% vs 79.2%, P = 0.001), as was joint pain severity, and the difference in pain between randomization groups persisted through year 3. However, joint swelling frequency was higher in the estrogen-alone group (42.1% vs 39.7%, P = 0.02). Adherence-adjusted analyses strengthen estrogen's association with reduced joint pain but attenuate estrogen's association with increased joint swelling. CONCLUSIONS: The current findings suggest that estrogen-alone use in postmenopausal women results in a modest but sustained reduction in the frequency of joint pain.

    View details for PubMedID 23511705

  • Demographic and health factors associated with enrollment in posttrial studies: The women's health initiative hormone therapy trials. Clinical trials Espeland, M. A., Pettinger, M., Falkner, K. L., Shumaker, S. A., Limacher, M., Thomas, F., Weaver, K. E., Stefanick, M. L., McQuellon, C., Hunt, J. R., Johnson, K. C. 2013; 10 (3): 463-472

    Abstract

    After clinical trials end, continued follow-up of the assembled cohort often is desirable for additional research. Factors influencing participants' decisions to consent to additional follow-up and how these shape posttrial cohorts have not been broadly studied.We examined how two re-enrollment campaigns and the passage of time altered features of the posttrial cohorts compared with the original Women's Health Initiative (WHI) Hormone Therapy clinical trials.We examined associations that markers of sociodemography, health, lifestyle, and on-trial experiences had with re-enrollment and contrasted the characteristics of successive posttrial cohorts with those of the original enrollees.The posttrial enrollment campaigns re-enrolled 81.1% and 82.5% of available women, respectively. Women who re-enrolled tended to have better health characteristics than those not re-enrolled. Compared to women of comparable age in the original cohort, women retained for the second posttrial follow-up less often had a history of cardiovascular disease (odds ratio (OR) = 0.36), hypertension (OR = 0.57), diabetes (OR = 0.59), or measured cognitive deficit (OR = 0.40). These women more often had graduated from high school (OR = 1.72) and had participated in other WHI trials (OR = 1.76).We have examined experience with creating follow-up cohorts from participants in a single study. Thus, our findings may not apply to other cohorts and protocols.Posttrial enrollment in follow-up studies can be successful; however, the characteristics of the resulting cohort may differ substantially from the originally assembled group of trial participants. Collection during the original trial of potential predictors of differential re-enrollment may strengthen interpretation of findings.

    View details for DOI 10.1177/1740774513477931

    View details for PubMedID 23480899

  • Effects of Postmenopausal Hormone Therapy on Incident Atrial Fibrillation The Women's Health Initiative Randomized Controlled Trials CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Perez, M. V., Wang, P. J., Larson, J. C., Virnig, B. A., Cochrane, B., Curb, J. D., Klein, L., Manson, J. E., Martin, L. W., Robinson, J., Wassertheil-Smoller, S., Stefanick, M. L. 2012; 5 (6): 1108-1116

    Abstract

    Atrial fibrillation (AF) is less prevalent in women versus men, but associated with higher risks of stroke and death in women. The role hormone therapy plays in AF is not well understood.The Women's Health Initiative randomized postmenopausal women to placebo or conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) if they had a uterus (N=16 608) or to conjugated equine estrogens only if they had prior hysterectomy (N=10 739). Incident AF was identified by ECG and diagnosis codes from Medicare claims or hospitalization records. Hazard ratios for incident AF were estimated using Cox proportional hazards regression. After excluding participants with baseline AF, there were 611 incident AF cases over a mean of 5.6 years among 16 128 estrogen plus progestin participants, and 683 cases over a mean of 7.1 years among 10 251 conjugated equine estrogens alone participants. Incident AF was more frequent in the active groups of both trials, reaching statistical significance in the trial of conjugated equine estrogens alone in women with prior hysterectomy (hazard ratio, 1.17; CI, 1.00-1.36; P=0.045) and in the pooled analysis (hazard ratio, 1.12; CI, 1.00-1.24; P=0.05), but not in the estrogen plus progestin trial (hazard ratio, 1.07; CI, 0.91-1.25; P=0.44). These results were only minimally affected by adjustment for incident stroke, coronary heart disease, and heart failure.Incident AF was modestly elevated in hysterectomized women randomized to postmenopausal E-alone, and in the pooled group randomized to E-alone or estrogen plus progestin. The trend in women with intact uterus receiving estrogen plus progestin, considered separately, was not statistically significant.ClinicalTrials.gov; Identifier: NCT00000611.

    View details for DOI 10.1161/CIRCEP.112.972224

    View details for Web of Science ID 000313586900018

    View details for PubMedID 23169946

  • The Association of Concurrent Vitamin D and Sex Hormone Deficiency With Bone Loss and Fracture Risk in Older Men: The Osteoporotic Fractures in Men (MrOS) Study JOURNAL OF BONE AND MINERAL RESEARCH Barrett-Connor, E., Laughlin, G. A., Li, H., Nielson, C. M., Wang, P. Y., Dam, T. T., Cauley, J. A., Ensrud, K. E., Stefanick, M. L., Lau, E., Hoffman, A. R., Orwoll, E. S. 2012; 27 (11): 2306-2313

    Abstract

    Low 25-hydroxyvitamin D (VitD), low sex hormones (SH), and high sex hormone binding globulin (SHBG) levels are common in older men. We tested the hypothesis that combinations of low VitD, low SH, and high SHBG would have a synergistic effect on bone mineral density (BMD), bone loss, and fracture risk in older men. Participants were a random subsample of 1468 men (mean age 74 years) from the Osteoporotic Fractures in Men Study (MrOS) plus 278 MrOS men with incident nonspine fractures studied in a case-cohort design. "Abnormal" was defined as lowest quartile for VitD (<20 ng/mL), bioavailable testosterone (BioT, <163 ng/dL), and bioavailable estradiol (BioE, <11 pg/mL); and highest quartile for SHBG (>59 nM). Overall, 10% had isolated VitD deficiency; 40% had only low SH or high SHBG; 15% had both SH/SHBG and VitD abnormality; and 35% had no abnormality. Compared to men with all normal levels, those with both SH/SHBG and VitD abnormality tended to be older, more obese, and to report less physical activity. Isolated VitD deficiency, and low BioT with or without low VitD, was not significantly related to skeletal measures. The combination of VitD deficiency with low BioE and/or high SHBG was associated with significantly lower baseline BMD and higher annualized rates of hip bone loss than SH abnormalities alone or no abnormality. Compared to men with all normal levels, the multivariate-adjusted hazard ratio (95% confidence interval [CI]) for incident nonspine fracture during 4.6-year median follow-up was 1.2 (0.8-1.8) for low VitD alone; 1.3 (0.9-1.9) for low BioE and/or high SHBG alone; and 1.6 (1.1-2.5) for low BioE/high SHBG plus low VitD. In summary, adverse skeletal effects of low sex steroid levels were more pronounced in older men with low VitD levels. The presence of low VitD in the presence of low BioE/high SHBG may contribute substantially to poor skeletal health.

    View details for DOI 10.1002/jbmr.1697

    View details for Web of Science ID 000313729500011

    View details for PubMedID 22777902

  • Inferior physical performance tests in 10,998 men in the MrOS study is associated with recurrent falls AGE AND AGEING Karlsson, M. K., Ribom, E., Nilsson, J., Ljunggren, O., Ohlsson, C., Mellstrom, D., Lorentzon, M., Mallmin, H., Stefanick, M., Lapidus, J., Leung, P. C., Kwok, A., Barrett-Connor, E., Orwoll, E., Rosengren, B. E. 2012; 41 (6): 740-746

    Abstract

    recurrent fallers are at especially high risk for injuries.to study whether tests of physical performance are associated with recurrent falls.a total of 10,998 men aged 65 years or above.questionnaires evaluated falls sustained 12 months preceding testing of grip strength, timed stand, 6-m walk and 20-cm narrow walk test. Means with 95% confidence interval (95% CI) are reported. P < 0.01 is a statistically significant difference.in comparison to both occasional fallers and non-fallers, recurrent fallers performed more poorly on all the physical ability tests (all P < 0.001). A score below -2 standard deviations (SDs) in the right-hand grip strength test was associated with an odds ratio of 2.4 (95% CI 1.7, 3.4) for having had recurrent falls compared with having had no fall and of 2.0 (95% CI 1.3, 3.4) for having had recurrent falls compared with having had an occasional fall.low performance in physical ability tests are in elderly men associated with recurrent falls.

    View details for DOI 10.1093/ageing/afs104

    View details for Web of Science ID 000310153100009

    View details for PubMedID 22923607

  • A low-fat dietary pattern and risk of metabolic syndrome in postmenopausal women: The Women's Health Initiative METABOLISM-CLINICAL AND EXPERIMENTAL Neuhouser, M. L., Howard, B., Lu, J., Tinker, L. F., Van Horn, L., Caan, B., Rohan, T., Stefanick, M. L., Thomson, C. A. 2012; 61 (11): 1572-1581

    Abstract

    Nutrition plays an important role in metabolic syndrome etiology. We examined whether the Women's Health Initiative (WHI) Dietary Modification Trial influenced metabolic syndrome risk.48,835 postmenopausal women aged 50-79 years were randomized to a low-fat (20% energy from fat) diet (intervention) or usual diet (comparison) for a mean of 8.1 years. Blood pressure, waist circumference and fasting blood measures of glucose, HDL-cholesterol and triglycerides were measured on a subsample (n=2816) at baseline and years 1, 3 and 6 post-randomization. Logistic regression estimated associations of the intervention with metabolic syndrome risk and use of cholesterol-lowering and hypertension medications. Multivariate linear regression tested associations between the intervention and metabolic syndrome components.At year 3, but not years 1 or 6, women in the intervention group (vs. comparison) had a non-statistically significant lower risk of metabolic syndrome (OR=0.83, 95%CI 0.59-1.18). Linear regression models simultaneously modeling the five metabolic syndrome components revealed significant associations of the intervention with metabolic syndrome at year 1 (p<0.0001), but not years 3 (p=0.19) and 6 (p=0.17). Analyses restricted to intervention-adherent participants strengthened associations at years 3 (p=0.05) and 6 (p=0.06). Cholesterol-lowering and hypertension medication use was 19% lower at year 1 for intervention vs. comparison group women (OR=0.81, 95% CI 0.60-1.09).Over the entire trial, fewer intervention vs. comparison participants used these medications (26.0% vs. 29.9%), although results were not statistically significant (p=0.89).The WHI low-fat diet may influence metabolic syndrome risk and decrease use of hypertension and cholesterol-lowering medications. Findings have potential for meaningful clinical translation.

    View details for DOI 10.1016/j.metabol.2012.04.007

    View details for Web of Science ID 000310557900010

    View details for PubMedID 22633601

  • Determinants of Racial/Ethnic Disparities in Incidence of Diabetes in Postmenopausal Women in the U.S. The Women's Health Initiative 1993-2009 DIABETES CARE Ma, Y., Hebert, J. R., Manson, J. E., Balasubramanian, R., Liu, S., LaMonte, M. J., Bird, C. E., Ockene, J. K., Qiao, Y., Olendzki, B., Schneider, K. L., Rosal, M. C., Sepavich, D. M., Wactawski-Wende, J., Stefanick, M. L., Phillips, L. S., Ockene, I. S., Kaplan, R. C., Sarto, G. E., Garcia, L., Howard, B. V. 2012; 35 (11): 2226-2234

    Abstract

    To examine determinants of racial/ethnic differences in diabetes incidence among postmenopausal women participating in the Women's Health Initiative.Data on race/ethnicity, baseline diabetes prevalence, and incident diabetes were obtained from 158,833 women recruited from 1993-1998 and followed through August 2009. The relationship between race/ethnicity, other potential risk factors, and the risk of incident diabetes was estimated using Cox proportional hazards models from which hazard ratios (HRs) and 95% CIs were computed.Participants were aged 63 years on average at baseline. The racial/ethnic distribution was 84.1% non-Hispanic white, 9.2% non-Hispanic black, 4.1% Hispanic, and 2.6% Asian. After an average of 10.4 years of follow-up, compared with whites and adjusting for potential confounders, the HRs for incident diabetes were 1.55 for blacks (95% CI 1.47-1.63), 1.67 for Hispanics (1.54-1.81), and 1.86 for Asians (1.68-2.06). Whites, blacks, and Hispanics with all factors (i.e., weight, physical activity, dietary quality, and smoking) in the low-risk category had 60, 69, and 63% lower risk for incident diabetes. Although contributions of different risk factors varied slightly by race/ethnicity, most findings were similar across groups, and women who had both a healthy weight and were in the highest tertile of physical activity had less than one-third the risk of diabetes compared with obese and inactive women.Despite large racial/ethnic differences in diabetes incidence, most variability could be attributed to lifestyle factors. Our findings show that the majority of diabetes cases are preventable, and risk reduction strategies can be effectively applied to all racial/ethnic groups.

    View details for DOI 10.2337/dc12-0412

    View details for Web of Science ID 000311424100024

    View details for PubMedID 22833490

  • A Prospective Study of Leukocyte Telomere Length and Risk of Type 2 Diabetes in Postmenopausal Women DIABETES You, N. Y., Chen, B. H., Song, Y., Lu, X., Chen, Y., Manson, J. E., Kang, M., Howard, B. V., Margolis, K. L., Curb, J. D., Phillips, L. S., Stefanick, M. L., Tinker, L. F., Liu, S. 2012; 61 (11): 2998-3004

    Abstract

    Telomere length (TL) has been implicated in the pathogenesis of age-related disorders. However, there are no prospective studies directly investigating the role of TL and relevant genes in diabetes development. In the multiethnic Women's Health Initiative, we identified 1,675 incident diabetes case participants in 6 years of follow-up and 2,382 control participants matched by age, ethnicity, clinical center, time of blood draw, and follow-up duration. Leukocyte TL at baseline was measured using quantitative PCR, and Mendelian randomization analysis was conducted to test whether TL is causally associated with diabetes risk. After adjustment for matching and known diabetes risk factors, odds ratios per 1-kilobase increment were 1.00 (95% CI 0.90-1.11) in whites, 0.95 (0.85-1.06) in blacks, 0.96 (0.79-1.17) in Hispanics, and 0.88 (0.70-1.10) in Asians. Of the 80 single nucleotide polymorphisms (SNPs) in nine genes involved in telomere regulation, 14 SNPs were predictive of TL, but none were significantly associated with diabetes risk. Using ethnicity-specific SNPs as randomization instruments, we observed no statistically significant association between TL and diabetes risk (P = 0.52). Although leukocyte TL was weakly associated with diabetes risk, this association was not independent of known risk factors. These prospective findings indicate limited clinical utility of TL in diabetes risk stratification among postmenopausal women.

    View details for DOI 10.2337/db12-0241

    View details for Web of Science ID 000312041600039

    View details for PubMedID 22829448

  • Change in hip bone mineral density and risk of subsequent fractures in older men JOURNAL OF BONE AND MINERAL RESEARCH Cawthon, P. M., Ewing, S. K., Mackey, D. C., Fink, H. A., Cummings, S. R., Ensrud, K. E., Stefanick, M. L., Bauer, D. C., Cauley, J. A., Orwoll, E. S. 2012; 27 (10): 2179-2188

    Abstract

    Low bone mineral density (BMD) increases fracture risk; how changes in BMD influence fracture risk in older men is uncertain. BMD was assessed at two to three time points over 4.6 years using dual-energy X-ray absorptiometry (DXA) for 4470 men aged ?65 years in the Osteoporotic Fractures in Men (MrOS) Study. Change in femoral neck BMD was estimated using mixed effects linear regression models. BMD change was categorized as "accelerated" (?-0.034?g/cm(2) ), "expected" (between 0 and -0.034?g/cm(2) ), or "maintained" (?0?g/cm(2) ). Fractures were adjudicated by central medical record review. Multivariate proportional hazards models estimated the risk of hip, nonspine/nonhip, and nonspine fracture over 4.5 years after the final BMD measure, during which time 371 (8.3%) men experienced at least one nonspine fracture, including 78 (1.7%) hip fractures. Men with accelerated femoral neck BMD loss had an increased risk of nonspine (hazard ratio [HR]?=?2.0; 95% confidence interval [CI] 1.4-2.8); nonspine/nonhip (HR?=?1.6; 95% CI 1.1-2.3); and hip fracture (HR?=?6.3; 95% CI 2.7-14.8) compared with men who maintained BMD over time. No difference in risk was seen for men with expected loss. Adjustment for the initial BMD measure did not alter the results. Adjustment for the final BMD measure attenuated the change in BMD-nonspine fracture and the change in BMD-nonspine/nonhip relationships such that they were no longer significant, whereas the change in the BMD-hip fracture relationship was attenuated (HR?=?2.6; 95% CI 1.1-6.4). Total hip BMD change produced similar results. Accelerated decrease in BMD is a strong, independent risk factor for hip and other nonspine fractures in men.

    View details for DOI 10.1002/jbmr.1671

    View details for Web of Science ID 000308925800015

    View details for PubMedID 22648990

  • Effects of a dietary intervention and weight change on vasomotor symptoms in the Women's Health Initiative MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Kroenke, C. H., Caan, B. J., Stefanick, M. L., Anderson, G., Brzyski, R., Johnson, K. C., Leblanc, E., Lee, C., La Croix, A. Z., Park, H. L., Sims, S. T., Vitolins, M., Wallace, R. 2012; 19 (9): 980-988

    Abstract

    The aim of this study was to determine whether a dietary intervention designed to reduce fat intake and increase intake of fruit, vegetables, and whole grains, and weight loss, reduces vasomotor symptoms (VMS; ie, hot flashes or night sweats) in postmenopausal women.We included 17,473 postmenopausal US women, ages 50 to 79 years, at baseline who participated in the Women's Health Initiative Dietary Modification trial and were not taking menopausal hormone therapy. Logistic regression was used to evaluate associations.In multivariate-adjusted analyses, with simultaneous adjustment for the intervention and weight change, assignment to the dietary intervention versus the control arm was significantly (odds ratio [OR], 1.14; 95% CI, 1.01-1.28) related to a higher likelihood of symptom elimination among women with VMS at baseline. In addition, women with symptoms at baseline who lost 10 lb or more (OR, 1.23; 95% CI, 1.05-1.46) or lost 10% or more of their baseline body weight (OR, 1.56; 95% CI, 1.21-2.02) between baseline and year 1 were significantly more likely to eliminate VMS compared with those who maintained weight. Upon examining the joint effect of the dietary modification and weight loss, compared with women in the control arm who maintained weight, women who lost substantial weight (? 10%) as a part of the intervention (OR, 1.89; 95% CI, 1.39-2.57) but not as part of the control arm (OR, 1.40; 95% CI, 0.92-2.13) were significantly more likely to end VMS, although these two groups did not differ significantly from each other. Large weight loss (>22 lb), but not dietary changes, was related to the elimination of moderate/severe VMS.Weight loss as part of a healthy dietary modification may help eliminate VMS among postmenopausal women.

    View details for DOI 10.1097/gme.0b013e31824f606e

    View details for Web of Science ID 000308415500008

    View details for PubMedID 22781782

  • Alcohol consumption and body weight change in postmenopausal women: results from the Women's Health Initiative INTERNATIONAL JOURNAL OF OBESITY Thomson, C. A., Wertheim, B. C., Hingle, M., Wang, L., Neuhouser, M. L., Gong, Z., Garcia, L., Stefanick, M. L., Manson, J. E. 2012; 36 (9): 1158-1164

    Abstract

    To determine whether alcohol consumption is associated with incident overweight or obesity in normal-weight, postmenopausal women.Prospective cohort study considering baseline alcohol consumption and subsequent weight change over 7 years.15,920 normal-weight (body mass index (BMI): 18.5 to <25?kg?m(-2)), postmenopausal women enrolled in the Women's Health Initiative Clinical Trial.Body weight change, and incident overweight and obesity (BMI, 25.0 to <30 and ? 30?kg?m(-2)) over 7 years.One-third of the 13,822 women included in the analytical cohort reported no alcohol consumption. BMI differed little between abstainers (22.8±1.58?kg?m(-2)) and alcohol consumers in the upper quintile (22.7±1.53?kg?m(-2)). Among normal-weight women, the risk of becoming overweight or obese over a 7-year follow-up period was 35% or 88% lower, respectively, for women in the upper quintile of alcohol intake relative to abstainers (hazard ratio (HR), 0.65; 95% confidence interval (CI), 0.58-0.73; or HR, 0.12; 95% CI, 0.05-0.25, respectively). Risk for overweight and obesity was not significantly modified by age. Wine consumption showed the greatest protective association for risk of overweight (HR, 0.75; 95% CI, 0.68-0.84), followed by liquor (HR, 0.85; 95% CI, 0.78-0.93) and beer (HR, 0.90; 95% CI, 0.82-1.00).Postmenopausal women of normal weight who report moderate alcohol intake have a reduced risk of becoming overweight or obese over time. Perhaps, weight control measures in this population should target behaviors other than reduction in alcohol for those of normal BMI consuming moderate amounts.

    View details for DOI 10.1038/ijo.2012.84

    View details for Web of Science ID 000308631400004

    View details for PubMedID 22689071

  • A longitudinal study of the metabolic syndrome and risk of colorectal cancer in postmenopausal women EUROPEAN JOURNAL OF CANCER PREVENTION Kabat, G. C., Kim, M. Y., Peters, U., Stefanick, M., Hou, L., Wactawski-Wende, J., Messina, C., Shikany, J. M., Rohan, T. E. 2012; 21 (4): 326-332

    Abstract

    The metabolic syndrome is associated with increased risk of diabetes and coronary heart disease. Although higher BMI and other related factors have been frequently associated with colorectal cancer, whether the metabolic syndrome is associated with the risk of colorectal cancer is unclear. We therefore assessed the association of the metabolic syndrome with the risk of colorectal cancer in a subsample of participants of the Women's Health Initiative who had repeated measurements of the components of the syndrome at baseline and during follow-up. Women with diabetes at baseline enrollment were excluded. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) at baseline and in time-dependent analyses. Among 4862 eligible women, 81 incident cases of colorectal cancer were identified over a median follow-up of 12 years. Presence of the metabolic syndrome at baseline was associated with increased risk of colorectal cancer (HR 2.15, 95% CI 1.30-3.53) and colon cancer (HR 2.28, 95% CI 1.31-3.98). These associations were largely explained by positive associations of serum glucose and systolic blood pressure with both outcomes. Time-dependent covariate analyses supported the baseline findings. Our results suggest that the positive association of the metabolic syndrome with risk of colorectal cancer is largely accounted for by serum glucose levels and systolic blood pressure. The biological mechanism underlying these associations remains to be clarified.

    View details for DOI 10.1097/CEJ.0b013e32834dbc81

    View details for Web of Science ID 000304528400003

    View details for PubMedID 22044849

  • The 2010 North American Menopause Society position statement on hormone therapy goes beyond the available evidence MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Anderson, G., LaCroix, A., Limacher, M., Prentice, R., Stefanick, M., Wassertheil-Smoller, S., Rossouw, J. 2012; 19 (7): 835-836

    View details for DOI 10.1097/gme.0b013e3182594f76

    View details for Web of Science ID 000305900100019

    View details for PubMedID 22668818

  • Physical Activity and Inflammation in a Multiethnic Cohort of Women MEDICINE AND SCIENCE IN SPORTS AND EXERCISE Lee, I., Sesso, H. D., Ridker, P. M., Mouton, C. P., Stefanick, M. L., Manson, J. E. 2012; 44 (6): 1088-1096

    Abstract

    Many cross-sectional studies using data from a single time point have reported that higher levels of physical activity or fitness are associated with lower levels of inflammatory markers, but data examining change are limited, as are race/ethnicity-specific data. The purpose of this study was to examine the associations between physical activity and inflammation assessed at two time points among women of different race/ethnicities.A total of 1355 postmenopausal women (301 whites, 300 blacks, 300 Hispanics, 300 Asians/Pacific Islanders, and 154 American Indians) age 50-79 yr were studied. Participants were from 40 US cities and were free of cardiovascular disease and cancer. At baseline and year 3, women reported their recreational physical activities and provided blood samples, which were analyzed for several inflammatory markers.In cross-sectional analyses, after adjusting for several potential confounders including body mass index, higher physical activity levels were generally related to lower inflammatory marker concentrations. For example, P values for a linear trend of lower C-reactive protein levels across physical activity tertiles at baseline were <0.0001 in all women and 0.94, 0.09, 0.002, 0.20, and 0.10, respectively, for the five race/ethnic groups listed above. For interleukin 6, the corresponding P values were <0.0001, 0.0007, 0.01, 0.03, 0.37, and 0.004, respectively, at baseline. Relationships at year 3 were similar to baseline. However, there was no relation between changes in physical activity and changes in inflammatory markers during the 3-yr period.Among middle-age and older women overall, there were strong, inverse, cross-sectional associations between physical activity level and inflammatory markers. However, changes in inflammatory markers were unrelated to changes in physical activity. These data suggest a noncausal association between physical activity and inflammatory markers.

    View details for DOI 10.1249/MSS.0b013e318242b11a

    View details for Web of Science ID 000304227100015

    View details for PubMedID 22595984

  • Inferior physical performance test results of 10,998 men in the MrOS Study is associated with high fracture risk AGE AND AGEING Rosengren, B. E., Ribom, E. L., Nilsson, J., Mallmin, H., Ljunggren, O., Ohlsson, C., Mellstrom, D., Lorentzon, M., Stefanick, M., Lapidus, J., Leung, P. C., Kwok, A., Barrett-Connor, E., Orwoll, E., Karlsson, M. K. 2012; 41 (3): 339-344

    Abstract

    most fractures are preceded by falls.the aim of this study was to determine whether tests of physical performance are associated with fractures. Subjects: a total of 10,998 men aged 65 years or above were recruited.questionnaires evaluated falls sustained 12 months before administration of the grip strength test, the timed stand test, the six-metre walk test and the twenty-centimetre narrow walk test. Means with 95% confidence interval (95% CI) are reported. P < 0.05 is a statistically significant difference.fallers with a fracture performed worse than non-fallers on all tests (all P < 0.001). Fallers with a fracture performed worse than fallers with no fractures both on the right-hand-grip strength test and on the six-metre walk test (P < 0.001). A score below -2 standard deviations in the right-hand-grip strength test was associated with an odds ratio of 3.9 (95% CI: 2.1-7.4) for having had a fall with a fracture compared with having had no fall and with an odds ratio of 2.6 (95% CI: 1.3-5.2) for having had a fall with a fracture compared with having had a fall with no fracture.the right-hand-grip strength test and the six-metre walk test performed by old men help discriminate fallers with a fracture from both fallers with no fracture and non-fallers.

    View details for DOI 10.1093/ageing/afs010

    View details for Web of Science ID 000303335000011

    View details for PubMedID 22314696

  • Physical Activity and Body Mass: Changes in Younger versus Older Postmenopausal Women MEDICINE AND SCIENCE IN SPORTS AND EXERCISE Sims, S. T., Larson, J. C., LaMonte, M. J., Michael, Y. L., Martin, L. W., Johnson, K. C., Sarto, G. E., Stefanick, M. L. 2012; 44 (1): 89-97

    Abstract

    The study's purpose was to investigate the relationship of sedentary (? 100 MET · min · wk(-1)), low (>100-500 MET · min · wk(-1)), moderate (>500-1200 MET · min · wk(-1)), and high (>1200 MET · min · wk(-1)) habitual physical activity with body weight, body mass index, and measures of fat distribution (waist-to-hip ratio) in postmenopausal women by age decades.A prospective cohort study of 58,610 postmenopausal women age 50-79 yr weighed annually during 8 yr at one of 40 US clinical centers was analyzed to determine the relationship of high versus low habitual physical activity with changes in body weight and fat distribution by age group.Among women age 50-59 yr, there was significant weight loss in those expending >500-1200 MET · min · wk(-1) (coefficient = -0.30, 95% confidence interval = -0.53 to -0.07) compared with the group expending ? 100 MET · min · wk(-1). Among women age 70-79 yr, higher physical activity was associated with less weight loss (coefficient = 0.34, 95% confidence interval = 0.04-0.63). Age at baseline significantly modified the association between physical activity and total weight change, whereas baseline body mass index did not.High habitual physical activity is associated with less weight gain in younger postmenopausal women and less weight loss in older postmenopausal women. These findings suggest that promoting physical activity among postmenopausal women may be important for managing body weight changes that accompany aging.

    View details for DOI 10.1249/MSS.0b013e318227f906

    View details for Web of Science ID 000298377400012

    View details for PubMedID 21659897

  • Associations Between Sleep Architecture and Sleep-Disordered Breathing and Cognition in Older Community-Dwelling Men: The Osteoporotic Fractures in Men Sleep Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Blackwell, T., Yaffe, K., Ancoli-Israel, S., Redline, S., Ensrud, K. E., Stefanick, M. L., Laffan, A., Stone, K. L. 2011; 59 (12): 2217-2225

    Abstract

    To examine the association between sleep architecture, sleep-disordered breathing, and cognition in older men.Population-based cross-sectional study.Six clinical sites in the United States.Two thousand nine hundred nine community-dwelling men aged 67 and older who were not selected on the basis of sleep problems or cognitive impairment.Predictors were measured using in-home polysomnography: sleep architecture, nocturnal hypoxemia (any sleep time with arterial oxygen saturation <80%), apnea-hypopnea index (AHI), and arousal index. Cognitive outcomes were measured using the modified Mini-Mental State Examination (3MS), Trail-Making Test Part B (TMT-B), and the Digit Vigilance Test (DVT).Analyses adjusted for age, race, education, body mass index, lifestyle, comorbidities, and medication use showed that participants who spent less percentage of time in rapid eye movement (REM) sleep had lower levels of cognition; participants in the lowest quartile (<14.8%) took an average of 5.9 seconds longer on the TMT-B and 20.1 seconds longer on the DVT than those in the highest quartile (?23.7%). Similarly, greater percentage of time spent in Stage 1 sleep was related to poorer cognitive function. Participants in the highest quartile of Stage 1 sleep (?8.6%) had worse cognitive scores on average than those in the lowest quartile (<4.0%). Those with nocturnal hypoxemia took an average of 22.3 seconds longer to complete the DVT than those without, but no associations were found with 3MS or the TMT-B.Spending less percentage of time in REM sleep and greater percentage of time in Stage 1 sleep and having higher levels of nocturnal hypoxemia were associated with poorer cognition in older men. Further studies are needed to clarify the direction of these associations and to explore potential mechanisms.

    View details for DOI 10.1111/j.1532-5415.2011.03731.x

    View details for Web of Science ID 000298600300004

    View details for PubMedID 22188071

  • There is in elderly men a group difference between fallers and non-fallers in physical performance tests AGE AND AGEING Rosengren, B., Ribom, E. L., Nilsson, J., Ljunggren, O., Ohlsson, C., Mellstrom, D., Lorentzon, M., Mallmin, H., Stefanick, M. L., Lapidus, J., Leung, P. C., Kwok, A., Barrett-Connor, E., Orwoll, E., Karlsson, M. K. 2011; 40 (6): 744-749

    View details for DOI 10.1093/ageing/afr108

    View details for Web of Science ID 000296095300019

    View details for PubMedID 21914663

  • Interaction Between Smoking and Obesity and the Risk of Developing Breast Cancer Among Postmenopausal Women AMERICAN JOURNAL OF EPIDEMIOLOGY Luo, J., Horn, K., Ockene, J. K., Simon, M. S., Stefanick, M. L., Tong, E., Margolis, K. L. 2011; 174 (8): 919-928

    Abstract

    Obesity is a well-established risk factor for postmenopausal breast cancer. Recent studies suggest that smoking increases the risk of breast cancer. However, the effect of co-occurrence of smoking and obesity on breast cancer risk remains unclear. A total of 76,628 women aged 50-79 years enrolled in the Women's Health Initiative Observational Study were followed through August 14, 2009. Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals. Over an average 10.3 years of follow-up, 3,378 incident cases of invasive breast cancer were identified. The effect of smoking on the risk of developing invasive breast cancer was modified significantly by obesity status among postmenopausal women, regardless of whether the obesity status was defined by body mass index (P(interaction) = 0.01) or waist circumference (P(interaction) = 0.02). A significant association between smoking and breast cancer risk was noted in nonobese women (hazard ratio = 1.25, 95% confidence interval: 1.05, 1.47) but not in obese women (hazard ratio = 0.96, 95% confidence interval: 0.69, 1.34). In conclusion, this study suggests that the effect of smoking exposure on breast cancer risk was modified by obesity among postmenopausal women. The modification effect did not differ by general versus abdominal obesity.

    View details for DOI 10.1093/aje/kwr192

    View details for Web of Science ID 000295679700006

    View details for PubMedID 21878422

  • Menopausal Hormone Therapy and Risks of Melanoma and Nonmelanoma Skin Cancers: Women's Health Initiative Randomized Trials JOURNAL OF THE NATIONAL CANCER INSTITUTE Tang, J. Y., Spaunhurst, K. M., Chlebowski, R. T., Wactawski-Wende, J., Keiser, E., Thomas, F., Anderson, M. L., Zeitouni, N. C., Larson, J. C., Stefanick, M. L. 2011; 103 (19): 1469-1475

    Abstract

    Case-control studies have reported that exogenous estrogen use is associated with increased risk of skin cancer. The effects of menopausal hormone therapy on incidence of nonmelanoma skin cancer and melanoma were evaluated in post hoc analyses of the Women's Health Initiative randomized placebo-controlled hormone therapy trials of combined estrogen plus progestin (E + P) and estrogen only (E-alone).Postmenopausal women aged 50-79 years were randomly assigned to conjugated equine estrogen (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo in the E + P trial if they had an intact uterus (N = 16,608) or to conjugated equine estrogen alone or placebo in the E-alone trial if they had a hysterectomy (N = 10,739); the mean follow-up was 5.6 and 7.1 years, respectively. Incident nonmelanoma skin cancers (n = 980 [E + P trial]; n = 820 [E-alone trial]) and melanomas (n = 57 [E + P trial]; n =38 [E-alone trial]) were ascertained by self-report. Incident cases of cutaneous malignant melanoma were confirmed by physician review of medical records. Incidences of nonmelanoma skin cancer and melanoma were compared between the two randomization groups within each trial using hazard ratios (HRs), with corresponding 95% confidence intervals (CIs) and Wald statistic P values from Cox proportional hazards models. All statistical tests were two-sided.Rates of incident nonmelanoma skin cancer and melanoma were similar between the active hormone (combined analysis of E + P and E-alone) and placebo groups (nonmelanoma skin cancer: HR = 0.98, 95% CI = 0.89 to 1.07; melanoma: HR = 0.92, 95% CI = 0.61 to 1.37). Results were similar for the E + P and E-alone trials when analyzed individually.Menopausal hormone therapy did not affect overall incidence of nonmelanoma skin cancer or melanoma. These findings do not support a role of menopausal estrogen, with or without progestin, in the development of skin cancer in postmenopausal women.

    View details for DOI 10.1093/jnci/djr333

    View details for Web of Science ID 000295683800011

    View details for PubMedID 21878677

  • Reproductive and menstrual factors and risk of ductal carcinoma in situ of the breast in a cohort of postmenopausal women CANCER CAUSES & CONTROL Kabat, G. C., Kim, M. Y., Woods, N. F., Habel, L. A., Messina, C. R., Wactawski-Wende, J., Stefanick, M. L., Chlebowski, R. T., Wassertheil-Smoller, S., Rohan, T. E. 2011; 22 (10): 1415-1424

    Abstract

    The contribution of menstrual and reproductive factors to risk of ductal carcinoma (DCIS) of the breast is poorly understood.The association between menstrual and reproductive factors and subsequent DCIS risk was examined in Women's Health Initiative (WHI) clinical trial participants, in which mammography was protocol mandated. The cohort consisted of 64,060 women, among whom 664 cases of DCIS were ascertained over a median follow-up of 12.0 years. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI).After adjustment for covariates, only older age at menopause (HR ? 55 vs. 45-54 : 1.39, 95% CI 1.08-1.79) was significantly associated with risk; however, greater parity (HR ? 5 live births vs. 0: 0.70, 95% CI 0.47-1.03), among parous women, and age at first live birth (HR ? 30 years relative to <20 years: 1.32, 95% CI 0.92-1.90) were of borderline significance. Age at menarche and months of breast-feeding were not associated with risk. Associations did not differ between high- and low-/moderate-grade DCIS, or by level of body mass index or family history of breast cancer; however, there was a suggestion that the associations of age at menopause, parity, and age at first live birth were limited to women who had ever used hormone therapy.Findings from this large cohort of postmenopausal women suggest that age at menopause, and possibly, age at first live birth, and parity are associated with risk of DCIS, whereas age at menarche and duration of breast-feeding are not.

    View details for DOI 10.1007/s10552-011-9814-8

    View details for Web of Science ID 000295992000007

    View details for PubMedID 21750889

  • Association of Sleep Characteristics and Cognition in Older Community-Dwelling Men: the MrOS Sleep Study SLEEP Blackwell, T., Yaffe, K., Ancoli-Israel, S., Redline, S., Ensrud, K. E., Stefanick, M. L., Laffan, A., Stone, K. L. 2011; 34 (10): 1347-1356

    Abstract

    To examine the association of objectively and subjectively measured sleep characteristics with cognition in older men.A population-based cross-sectional study.6 centers in the United States.3,132 community-dwelling older men (mean age 76.4 ± 5.6 years).None.Objectively measured sleep predictors from wrist actigraphy were total sleep time (TST), sleep efficiency (SE), and wake after sleep onset (WASO). Subjective sleep predictors were self-reported poor sleep (Pittsburgh Sleep Quality Index [PSQI] > 5), excessive daytime sleepiness (EDS, Epworth Sleepiness Scale Score > 10), and TST. Cognitive outcomes were measured with the Modified Mini-Mental State examination (3MS), the Trails B test, and the Digit Vigilance Test (DVT). After adjustment for multiple potential confounders, WASO was modestly related to poorer cognition. Compared to those with WASO < 90 min, men with WASO ? 90 min took 6.1 sec longer to complete the Trails B test and had a 0.9-point worse 3MS score, on average (P<0.05). Actigraphically measured long sleepers had a slightly worse 3MS score compared to those with 7-8 h of sleep, but had similar Trails B and DVT completion times. Compared to those who self-reported sleeping 7-8 h, long sleepers (>8 h) on average took 8.6 sec more to complete the Trails B test, had a 0.6-point worse 3MS score, and took 46 sec longer to complete the DVT (P<0.05). PSQI and EDS were not independently related to cognitive outcomes.There were modest cross-sectional associations of WASO and self-reported long sleep with cognition among older community-dwelling men. EDS and PSQI were not related to cognition.

    View details for DOI 10.5665/SLEEP.1276

    View details for Web of Science ID 000295624800011

    View details for PubMedID 21966066

  • Association of Incident Cardiovascular Disease With Periodic Limb Movements During Sleep in Older Men Outcomes of Sleep Disorders in Older Men (MrOS) Study CIRCULATION Koo, B. B., Blackwell, T., Ancoli-Israel, S., Stone, K. L., Stefanick, M. L., Redline, S. 2011; 124 (11): 1223-1231

    Abstract

    Periodic limb movements during sleep (PLMS) cause repetitive sympathetic activation and may be associated with increased cardiovascular risk. We hypothesized that PLMS frequency (periodic limb movement index [PLMI]) and PLMS arousal frequency (periodic limb movement arousal index [PLMAI]) are predictive of incident cardiovascular disease, including coronary heart disease, peripheral arterial disease, and cerebrovascular disease, in an elderly male cohort.A total of 2911 men in the observational Outcomes of Sleep Disorders in Older Men (MrOS) Sleep Study cohort underwent in-home polysomnography with PLMS measurement and were followed up for 4 years for the outcomes coronary heart disease, cerebrovascular disease, peripheral arterial disease, and all-cause cardiovascular disease, which included coronary heart disease, cerebrovascular disease, and peripheral arterial disease. Cox proportional hazards regression assessed the association between PLMI, PLMAI, and these outcomes. Models were minimally adjusted for age, clinic, and body mass index and then fully adjusted for conventional cardiovascular risk factors. During follow-up, 500 men experienced all-cause cardiovascular disease: 345 coronary heart disease, 117 cerebrovascular disease, and 98 peripheral arterial disease events. In fully adjusted models, men with PLMAI ?5 compared with the referent PLMA <1 group had a 1.26-fold increased relative hazard for all-cause cardiovascular disease. Similar findings were observed for PLMI and all-cause cardiovascular disease. For peripheral arterial disease, men with PLMI ?30 compared with the referent PLMI <5 group had a 2-fold increased relative hazard (95% confidence interval, 1.14 to 3.49; P=0.025). Compared with the referent group, men with PLMI ?30 had an increased risk of coronary heart disease (relative hazard, 1.31; 95% confidence interval, 1.01 to 1.70; P=0.045) after minimal adjustment, but this association was attenuated after further adjustments. After stratification, risk of incident all-cause cardiovascular disease among high-PLMI and high-PLMAI groups was significantly elevated only for men without prevalent hypertension (P for interactions <0.10).These findings provide evidence that PLMS frequency is associated with incident cardiovascular disease in community-dwelling elderly men.

    View details for DOI 10.1161/CIRCULATIONAHA.111.038968

    View details for Web of Science ID 000294779000016

    View details for PubMedID 21859975

  • Metabolic Syndrome and Physical Performance in Elderly Men: The Osteoporotic Fractures in Men Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Everson-Rose, S. A., Paudel, M., Taylor, B. C., Dam, T., Cawthon, P. M., Leblanc, E., Strotmeyer, E. S., Cauley, J. A., Stefanick, M. L., Barrett-Connor, E., Ensrud, K. E. 2011; 59 (8): 1376-1384

    Abstract

    To examine the association between metabolic syndrome (MetS) and objective measures of physical performance.Cross-sectional analysis of the cohort study, the Osteoporotic Fractures in Men Study.Six clinical sites in the United States.Five thousand four hundred fifty-seven ambulatory men (mean age 73.6 ± 5.9).Physical performance assessed according to grip strength, narrow walk speed, walking speed, and time to complete five repeated chair stands. Individual scores were converted to quintiles (worst=1 to best=5; unable to complete=0) and summed for an overall score (mean 11.6 ± 4.3, range, 1-20). MetS was defined according to World Health Organization criteria that include evidence of glucose dysregulation (insulin resistance, diabetes mellitus, or hyperinsulinemia) and at least two additional characteristics: high blood pressure, low high-density lipoprotein cholesterol, high triglycerides, obesity.More than one-quarter (26.3%) of participants met criteria for MetS. In separate linear regression models, four of five MetS components were related to performance (P<.001); only high blood pressure was unrelated. Men with MetS had a 1.1-point lower performance score (mean 10.8, 95% confidence interval (CI)=10.6-11.0) than men without MetS (mean 11.9, 95% CI=11.8-12.0) (P<.001), adjusting for age, race, education, and site. With further covariate adjustment, this difference was reduced but remained significant (?=-0.78, P<.001). A graded association was observed between number of MetS components (0, 1, 2, or ?3) and performance (P for trend <.001). Findings were similar excluding men with diabetes mellitus or obese men.Metabolic dysregulation is related to objectively assessed poorer physical performance in relatively healthy older men.

    View details for DOI 10.1111/j.1532-5415.2011.03518.x

    View details for Web of Science ID 000293980600002

    View details for PubMedID 21806561

  • Calcium Plus Vitamin D Supplementation and the Risk of Nonmelanoma and Melanoma Skin Cancer: Post Hoc Analyses of the Women's Health Initiative Randomized Controlled Trial JOURNAL OF CLINICAL ONCOLOGY Tang, J. Y., Fu, T., Leblanc, E., Manson, J. E., Feldman, D., Linos, E., Vitolins, M. Z., Zeitouni, N. C., Larson, J., Stefanick, M. L. 2011; 29 (22): 3078-3084

    Abstract

    In light of inverse relationships reported in observational studies of vitamin D intake and serum 25-hydroxyvitamin D levels with risk of nonmelanoma skin cancer (NMSC) and melanoma, we evaluated the effects of vitamin D combined with calcium supplementation on skin cancer in a randomized placebo-controlled trial.Postmenopausal women age 50 to 79 years (N = 36,282) enrolled onto the Women's Health Initiative (WHI) calcium/vitamin D clinical trial were randomly assigned to receive 1,000 mg of elemental calcium plus 400 IU of vitamin D3 (CaD) daily or placebo for a mean follow-up period of 7.0 years. NMSC and melanoma skin cancers were ascertained by annual self-report; melanoma skin cancers underwent physician adjudication.Neither incident NMSC nor melanoma rates differed between treatment (hazard ratio [HR], 1.02; 95% CI, 0.95 to 1.07) and placebo groups (HR, 0.86; 95% CI, 0.64 to 1.16). In subgroup analyses, women with history of NMSC assigned to CaD had a reduced risk of melanoma versus those receiving placebo (HR, 0.43; 95% CI, 0.21 to 0.90; P(interaction) = .038), which was not observed in women without history of NMSC.Vitamin D supplementation at a relatively low dose plus calcium did not reduce the overall incidence of NMSC or melanoma. However, in women with history of NMSC, CaD supplementation reduced melanoma risk, suggesting a potential role for calcium and vitamin D supplements in this high-risk group. Results from this post hoc subgroup analysis should be interpreted with caution but warrant additional investigation.

    View details for DOI 10.1200/JCO.2011.34.5967

    View details for Web of Science ID 000293222200029

    View details for PubMedID 21709199

  • Vasomotor symptoms and cardiovascular events in postmenopausal women MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Szmuilowicz, E. D., Manson, J. E., Rossouw, J. E., Howard, B. V., Margolis, K. L., Greep, N. C., Brzyski, R. G., Stefanick, M. L., O'Sullivan, M. J., Wu, C., Allison, M., Grobbee, D. E., Johnson, K. C., Ockene, J. K., Rodriguez, B. L., Sarto, G. E., Vitolins, M. Z., Seely, E. W. 2011; 18 (6): 603-610

    Abstract

    Emerging evidence suggests that women with menopausal vasomotor symptoms (VMS) have increased cardiovascular disease (CVD) risk as measured by surrogate markers. We investigated the relationships between VMS and clinical CVD events and all-cause mortality in the Women's Health Initiative Observational Study (WHI-OS).We compared the risk of incident CVD events and all-cause mortality between four groups of women (total N = 60,027): (1) no VMS at menopause onset and no VMS at WHI-OS enrollment (no VMS [referent group]), (2) VMS at menopause onset but not at WHI-OS enrollment (early VMS), (3) VMS at both menopause onset and WHI-OS enrollment (persistent VMS [early and late]), and (4) VMS at WHI-OS enrollment but not at menopause onset (late VMS).For women with early VMS (n = 24,753), compared with no VMS (n = 18,799), hazard ratios (95% CIs) in fully adjusted models were as follows: major coronary heart disease (CHD), 0.94 (0.84-1.06); stroke, 0.83 (0.72-0.96); total CVD, 0.89 (0.81-0.97); and all-cause mortality, 0.92 (0.85-0.99). For women with persistent VMS (n = 15,084), there was no significant association with clinical events. For women with late VMS (n = 1,391), compared with no VMS, hazard ratios (95% CIs) were as follows: major CHD, 1.32 (1.01-1.71); stroke, 1.14 (0.82-1.59); total CVD, 1.23 (1.00-1.52); and all-cause mortality, 1.29 (1.08-1.54).Early VMS were not associated with increased CVD risk. Rather, early VMS were associated with decreased risk of stroke, total CVD events, and all-cause mortality. Late VMS were associated with increased CHD risk and all-cause mortality. The predictive value of VMS for clinical CVD events may vary with the onset of VMS at different stages of menopause. Further research examining the mechanisms underlying these associations is needed. Future studies will also be necessary to investigate whether VMS that develop for the first time in the later postmenopausal years represent a pathophysiologic process distinct from the classic perimenopausal VMS.

    View details for DOI 10.1097/gme.0b013e3182014849

    View details for Web of Science ID 000291004400005

    View details for PubMedID 21358352

  • Obesity in relation to endometrial cancer risk and disease characteristics in the Women's Health Initiative GYNECOLOGIC ONCOLOGY Reeves, K. W., Carter, G. C., Rodabough, R. J., Lane, D., Mcneeley, S. G., Stefanick, M. L., Paskett, E. D. 2011; 121 (2): 376-382

    Abstract

    Obesity increases endometrial cancer risk, yet its impact on disease stage and grade is unclear. We prospectively examined the effects of body mass index (BMI) and waist-to-hip ratio (WHR) on incidence, stage, and grade of endometrial cancer.We studied 86937 postmenopausal women enrolled in the Women's Health Initiative. Height, weight, and waist and hip circumference were measured at baseline. Endometrial cancer cases were adjudicated by trained physicians and pathology reports were used to determine stage and grade. Cox proportional hazards models generated hazard ratios (HR) for associations between BMI and WHR and risk of endometrial cancer. Logistic regression was used to evaluate associations between BMI and WHR and disease stage and grade.During a mean 7.8 (standard deviation 1.6) years of follow-up, 806 women were diagnosed with endometrial cancer. Although incidence was higher among Whites, stage and grade were similar between Whites and Blacks. Elevated BMI (HR 1.76, 95% confidence interval [CI] 1.41-2.19) and WHR (HR 1.33, 95% CI 1.04-1.70) increased endometrial cancer risk when comparing women in the highest and lowest categories. No associations were observed between BMI or WHR and disease stage or grade.Obesity increases endometrial cancer risk independent of other factors but is not associated with stage or grade of disease. These findings support and validate previous reports. Future research should evaluate the impact of obesity on racial disparities in endometrial cancer survival.

    View details for DOI 10.1016/j.ygyno.2011.01.027

    View details for Web of Science ID 000290292100026

    View details for PubMedID 21324514

  • Oophorectomy vs Ovarian Conservation With Hysterectomy Cardiovascular Disease, Hip Fracture, and Cancer in the Women's Health Initiative Observational Study ARCHIVES OF INTERNAL MEDICINE Jacoby, V. L., Grady, D., Wactawski-Wende, J., Manson, J. E., Allison, M. A., Kuppermann, M., Sarto, G. E., Robbins, J., Phillips, L., Martin, L. W., O'Sullivan, M. J., Jackson, R., Rodabough, R. J., Stefanick, M. L. 2011; 171 (8): 760-768

    Abstract

    Elective bilateral salpingo-oophorectomy (BSO) is routinely performed with hysterectomy for benign conditions despite conflicting data on long-term outcomes.This is a prospective cohort of 25 448 postmenopausal women aged 50 to 79 years enrolled in the Women's Health Initiative Observational Study who had a history of hysterectomy and BSO (n = 14 254 [56.0%]) or hysterectomy with ovarian conservation (n = 11 194 [44.0%]) and no family history of ovarian cancer. Multivariable Cox proportional hazards regression models were used to examine the effect of BSO on incident cardiovascular disease, hip fracture, cancer, and death.Current or past use of estrogen and/or progestin was common irrespective of BSO status (78.6% of cohort). In multivariable analyses, BSO was not associated with an increased risk of fatal and nonfatal coronary heart disease (hazard ratio, 1.00 [95% confidence interval, 0.85-1.18]), coronary artery bypass graft/percutaneous transluminal coronary angioplasty (0.95 [0.82-1.10]), stroke (1.04 [0.87-1.24]), total cardiovascular disease (0.99 [0.91-1.09]), hip fracture (0.83 [0.63-1.10]), or death (0.98 [0.87-1.10]). Bilateral salpingo-oophorectomy decreased incident ovarian cancer (0.02% in the BSO group; 0.33% in the ovarian conservation group; number needed to treat, 323) during a mean (SD) follow-up of 7.6 (1.6) years, but there were no significant associations for breast, colorectal, or lung cancer.In this large prospective cohort study, BSO decreased the risk of ovarian cancer compared with hysterectomy and ovarian conservation, but incident ovarian cancer was rare in both groups. Our findings suggest that BSO may not have an adverse effect on cardiovascular health, hip fracture, cancer, or total mortality compared with hysterectomy and ovarian conservation.

    View details for Web of Science ID 000289853300008

    View details for PubMedID 21518944

  • Health Outcomes After Stopping Conjugated Equine Estrogens Among Postmenopausal Women With Prior Hysterectomy A Randomized Controlled Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LaCroix, A. Z., Chlebowski, R. T., Manson, J. E., Aragaki, A. K., Johnson, K. C., Martin, L., Margolis, K. L., Stefanick, M. L., Brzyski, R., Curb, J. D., Howard, B. V., Lewis, C. E., Wactawski-Wende, J. 2011; 305 (13): 1305-1314

    Abstract

    The Women's Health Initiative Estrogen-Alone Trial was stopped early after a mean of 7.1 years of follow-up because of an increased risk of stroke and little likelihood of altering the balance of risk to benefit by the planned trial termination date. Postintervention health outcomes have not been reported.To examine health outcomes associated with randomization to treatment with conjugated equine estrogens (CEE) among women with prior hysterectomy after a mean of 10.7 years of follow-up through August 2009.The intervention phase was a double-blind, placebo-controlled, randomized clinical trial of 0.625 mg/d of CEE compared with placebo in 10,739 US postmenopausal women aged 50 to 79 years with prior hysterectomy. Follow-up continued after the planned trial completion date among 7645 surviving participants (78%) who provided written consent.The primary outcomes were coronary heart disease (CHD) and invasive breast cancer. A global index of risks and benefits included these primary outcomes plus stroke, pulmonary embolism, colorectal cancer, hip fracture, and death.The postintervention risk (annualized rate) for CHD among women assigned to CEE was 0.64% compared with 0.67% in the placebo group (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.75-1.25), 0.26% vs 0.34%, respectively, for breast cancer (HR, 0.75; 95% CI, 0.51-1.09), and 1.47% vs 1.48%, respectively, for total mortality (HR, 1.00; 95% CI, 0.84-1.18). The risk of stroke was no longer elevated during the postintervention follow-up period and was 0.36% among women receiving CEE compared with 0.41% in the placebo group (HR, 0.89; 95% CI, 0.64-1.24), the risk of deep vein thrombosis was lower at 0.17% vs 0.27%, respectively (HR, 0.63; 95% CI, 0.41-0.98), and the risk of hip fracture did not differ significantly and was 0.36% vs 0.28%, respectively (HR, 1.27; 95% CI, 0.88-1.82). Over the entire follow-up, lower breast cancer incidence in the CEE group persisted and was 0.27% compared with 0.35% in the placebo group (HR, 0.77; 95% CI, 0.62-0.95). Health outcomes were more favorable for younger compared with older women for CHD (P = .05 for interaction), total myocardial infarction (P = .007 for interaction), colorectal cancer (P = .04 for interaction), total mortality (P = .04 for interaction), and global index of chronic diseases (P = .009 for interaction).Among postmenopausal women with prior hysterectomy followed up for 10.7 years, CEE use for a median of 5.9 years was not associated with an increased or decreased risk of CHD, deep vein thrombosis, stroke, hip fracture, colorectal cancer, or total mortality. A decreased risk of breast cancer persisted.clinicaltrials.gov Identifier: NCT00000611.

    View details for Web of Science ID 000289162400019

    View details for PubMedID 21467283

  • Physical Activity and Survival in Postmenopausal Women with Breast Cancer: Results from the Women's Health Initiative CANCER PREVENTION RESEARCH Irwin, M. L., McTiernan, A., Manson, J. E., Thomson, C. A., Sternfeld, B., Stefanick, M. L., Wactawski-Wende, J., Craft, L., Lane, D., Martin, L. W., Chlebowski, R. 2011; 4 (4): 522-529

    Abstract

    Although studies have shown that physically active breast cancer survivors have lower all-cause mortality, the association between change in physical activity from before to after diagnosis and mortality is not clear. We examined associations among pre- and postdiagnosis physical activity, change in pre- to postdiagnosis physical activity, and all-cause and breast cancer-specific mortality in postmenopausal women. A longitudinal study of 4,643 women diagnosed with invasive breast cancer after entry into the Women's Health Initiative study of postmenopausal women. Physical activity from recreation and walking was determined at baseline (prediagnosis) and after diagnosis (assessed at the 3 or 6 years post-baseline visit). Women participating in 9 MET-h/wk or more (? 3 h/wk of fast walking) of physical activity before diagnosis had a lower all-cause mortality (HR = 0.61; 95% CI, 0.44-0.87; P = 0.01) compared with inactive women in multivariable adjusted analyses. Women participating in ? 9 or more MET-h/wk of physical activity after diagnosis had lower breast cancer mortality (HR = 0.61; 95% CI, 0.35-0.99; P = 0.049) and lower all-cause mortality (HR = 0.54; 95% CI, 0.38-0.79; P < 0.01). Women who increased or maintained physical activity of 9 or more MET-h/wk after diagnosis had lower all-cause mortality (HR = 0.67; 95% CI, 0.46-0.96) even if they were inactive before diagnosis. High levels of physical activity may improve survival in postmenopausal women with breast cancer, even among those reporting low physical activity prior to diagnosis. Women diagnosed with breast cancer should be encouraged to initiate and maintain a program of physical activity.

    View details for DOI 10.1158/1940-6207.CAPR-10-0295

    View details for Web of Science ID 000289073700008

    View details for PubMedID 21464032

  • Trends in menopausal hormone therapy use of US office-based physicians, 2000-2009 MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Tsai, S. A., Stefanick, M. L., Stafford, R. S. 2011; 18 (4): 385-392

    Abstract

    The aim of this study was to evaluate recent trends and the adoption of practice recommendations for menopausal hormone therapy (MHT) use from 2001 to 2009 by formulation, dose, woman's age, and characteristics of physicians reporting MHT visits.The IMS Health (Plymouth Meeting PA) National Disease and Therapeutic Index physician survey data from 2001 to 2009 were analyzed for visits in which MHT use was reported by US office-based physicians. Estimated national volume of visits for which MHT use was reported.MHT use declined each year since 2002. Systemic MHT use fell from 16.3 million (M) visits in 2001 to 6.1 M visits in 2009. Declines were greatest for women 60 years or older (64%) but were also substantial for women younger than 50 years (59%) and women 50 to 59 years old (60%). Women 60 years or older accounted for 37% of MHT use. Lower dose product use increased modestly, from 0.7 M (2001) to 1.3 M (2009), as did vaginal MHT use, from 1.8 M (2001) to 2.4 M (2009). Declines in continuing systemic MHT use (65%) were greater than for newly initiated MHT use (51%). Compared with other physicians, obstetrician/gynecologists changed their practices less, thereby increasing their overall share of total MHT visits from 72% (2001) to 82% (2009).Total MHT use has steadily declined. Increased use of lower dose and vaginal products reflects clinical recommendations. Uptake of these products, however, has been modest, and substantial use of MHT continues in older women.

    View details for DOI 10.1097/gme.0b013e3181f43404

    View details for Web of Science ID 000288781800009

    View details for PubMedID 21127439

  • Nutrient Intake and Anemia Risk in the Women's Health Initiative Observational Study JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION Thomson, C. A., Stanaway, J. D., Neuhouser, M. L., Snetselaar, L. G., Stefanick, M. L., Arendell, L., Chen, Z. 2011; 111 (4): 532-541

    Abstract

    Nutrient-related anemia among postmenopausal women is preventable; recent data on prevalence are limited.To investigate the association between nutrient intakes and anemia prevalence, in relation to both incidence and persistence, in a longitudinal sample of postmenopausal women. We hypothesized that anemia prevalence, incidence, and persistence would be greater among women reporting lower intake of vitamin B-12, folate, and iron.Prospective cohort analysis.The observational cohort of the Women's Health Initiative, including 93,676 postmenopausal women, aged 50 to 79 years, who were recruited across the United States at 40 clinical study sites. Women were enrolled between 1993 and 1998; data collection for these analyses continued through 2000.Anemia was defined as a blood hemoglobin concentration of <12.0 g/dL (120.0 g/L). Persistent anemia was defined as anemia present at each measurement time point. Diet was assessed by food frequency questionnaire for iron, folate, B-12, red meat, and cold breakfast cereal; inadequacies were based on dietary reference intakes for women older than age 50 years.Descriptive statistics (mean ± standard deviation) were used to characterize the population demographics, anemia rates, and diet. Unconditional logistic regression was used to investigate associations between diet and incident and persistent anemia. Associations are presented as odds ratio and 95% confidence intervals.Anemia was identified in 3,979 (5.5%) of the cohort. Inadequate intakes of multiple anemia-associated nutrients were less frequent in non-Hispanic whites (7.4%) than other race/ethnic groups (inadequacies demonstrated in 14.6% to 16.3% of the sample). Age, body mass index, and smoking were associated with anemia. Women with anemia reported lower intakes of energy, protein, folate, vitamin B-12, iron, vitamin C, and red meat. Multiple (more than a single nutrient) dietary deficiencies were associated with a 21% greater risk of persistent anemia (odds ratio 1.21, 95% confidence interval 1.05 to 1.41) and three deficiencies resulted in a 44% increase in risk for persistent anemia (odds ratio 1.44, 95% confidence interval 1.20 to 1.73).Inadequate nutrient intake, a modifiable condition, is associated with greater risk for anemia in postmenopausal women participating in the Observational Study of the Women's Health Initiative. Efforts to identify and update incidence estimates for anemia-associated nutrient deficiencies in aging women should be undertaken.

    View details for DOI 10.1016/j.jada.2011.01.017

    View details for Web of Science ID 000289388200009

    View details for PubMedID 21443985

  • Poor physical health predicts time to additional breast cancer events and mortality in breast cancer survivors PSYCHO-ONCOLOGY Saquib, N., Pierce, J. P., Saquib, J., Flatt, S. W., Natarajan, L., Bardwell, W. A., Patterson, R. E., Stefanick, M. L., Thomson, C. A., Rock, C. L., Jones, L. A., Gold, E. B., Karanja, N., Parker, B. A. 2011; 20 (3): 252-259

    Abstract

    Health-related quality of life has been hypothesized to predict time to additional breast cancer events and all-cause mortality in breast cancer survivors.Women with early-stage breast cancer (n=2967) completed the SF-36 (mental and physical health-related quality of life) and standardized psychosocial questionnaires to assess social support, optimism, hostility, and depression prior to randomization into a dietary trial. Cox regression was performed to assess whether these measures of quality of life and psychosocial functioning predicted time to additional breast cancer events and all-cause mortality; hazard ratios were the measure of association.There were 492 additional breast cancer events and 301 deaths occurred over a median 7.3 years (range: 0.01-10.8 years) of follow-up. In multivariate models, poorer physical health was associated with both decreased time to additional breast cancer events and all-cause mortality (p trend=0.005 and 0.004, respectively), while greater hostility predicted additional breast cancer events only (p trend=0.03). None of the other psychosocial variables predicted either outcome. The hazard ratios comparing persons with poor (bottom two quintiles) to better (top three quintiles) physical health were 1.42 (95% CI: 1.16, 1.75) for decreased time to additional breast cancer events and 1.37 (95% CI: 1.08, 1.74) for all-cause mortality. Potentially modifiable factors associated with poor physical health included higher body mass index, lower physical activity, lower alcohol consumption, and more insomnia (p<0.05 for all).Interventions to improve physical health should be tested as a means to increase time to additional breast cancer events and mortality among breast cancer survivors.

    View details for DOI 10.1002/pon.1742

    View details for Web of Science ID 000288138200003

    View details for PubMedID 20878837

  • Biomarker-calibrated Energy and Protein Consumption and Cardiovascular Disease Risk Among Postmenopausal Women EPIDEMIOLOGY Prentice, R. L., Huang, Y., Kuller, L. H., Tinker, L. F., Van Horn, L., Stefanick, M. L., Sarto, G., Ockene, J., Johnson, K. C. 2011; 22 (2): 170-179

    Abstract

    Nutritional epidemiology cohort studies primarily use food frequency questionnaires (FFQs). In part because FFQs are more reliable for nutrient densities than for absolute nutrient consumption, reports from association studies typically present only nutrient density measures in relation to disease risk.We used objective biomarkers to correct FFQ assessments for measurement error, and examined absolute energy and protein consumption in relation to cardiovascular disease incidence. FFQs and subsequent physician-adjudicated cardiovascular disease incidence were assessed for 80,370 postmenopausal women in the age range 50-79 years at enrollment in the comparison group of the Dietary Modification Trial or the prospective Observational Study in the Women's Health Initiative. Urinary recovery biomarkers of energy and protein were obtained from a subsample of 544 women, with concurrent FFQ information.After biomarker correction, energy consumption was positively associated with coronary heart disease incidence (hazard ratio = 1.18; 95% confidence interval = 1.04-1.33, for 20% consumption increment) and protein density was inversely associated (0.85 [0.75-0.97]). The positive energy association appeared to be mediated by body fat accumulation. Ischemic stroke incidence was inversely associated with energy and protein consumption, but not with protein density.A positive association between energy and coronary heart disease risk can be attributed to body mass accumulation. Ischemic stroke risk is inversely associated with energy and protein consumption, possibly due to correlations between consumption and physical activity.

    View details for DOI 10.1097/EDE.0b013e31820839bc

    View details for Web of Science ID 000286970700007

    View details for PubMedID 21206366

  • Combined Impact of Geriatric Syndromes and Cardiometabolic Diseases on Measures of Functional Impairment JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Rosso, A. L., Eaton, C. B., Wallace, R., Gold, R., Curb, J. D., Stefanick, M. L., Ockene, J. K., Michael, Y. L. 2011; 66 (3): 349-354

    Abstract

    Examine the independent and joint effects of geriatric syndromes (GS) and cardiometabolic diseases (CMDs) on functional impairment.Cross-sectional analysis of baseline data from the Women's Health Initiative, including 62,829 women aged 65 years or older. GS (urinary incontinence, falls, and depression measured by the shortened Center for Epidemiological Studies-Depression scale/Diagnostic Interview Schedule screening instrument) and CMD (coronary artery disease, coronary heart failure, and diabetes) were self-reported. Physical and social functioning and general health subscales of the Short Form-36 dichotomized at the median for the study sample were used to assess functional impairment. Additive interaction between burden of GS and CMD was assessed using logistic regression models.Forty-three percent of women had at least one GS; 14.1% had at least one CMD; and 6.9% had at least one of each. Compared with women with no GS or CMD, women with one or more GS but no CMD were as likely to have physical functioning impairments (odds ratio [OR] = 1.79; 95% confidence interval [CI] = 1.73, 1.86) as those with CMD alone (OR = 1.97; CI = 1.84, 2.10). The association with social functioning was stronger for GS alone (OR = 2.10; CI = 2.02, 2.18) compared with CMD (OR = 1.60; CI = 1.50, 1.71). The association with general health was stronger for CMD alone (OR = 2.15; CI = 2.01, 2.29) compared with GS (OR = 1.68; CI = 1.62, 1.74). Significant interactions between GS and CMD were observed for all functional measures with 20%-30% of observed ORs attributable to additive interaction.GSs alone are associated with functional impairment in older women; the association is stronger in the presence of even one CMD.

    View details for DOI 10.1093/gerona/glq230

    View details for Web of Science ID 000288415800013

    View details for PubMedID 21317242

  • Reproductive History and Oral Contraceptive Use in Relation to Risk of Triple-Negative Breast Cancer JOURNAL OF THE NATIONAL CANCER INSTITUTE Phipps, A. I., Chlebowski, R. T., Prentice, R., McTiernan, A., Wactawski-Wende, J., Kuller, L. H., Adams-Campbell, L. L., Lane, D., Stefanick, M. L., Vitolins, M., Kabat, G. C., Rohan, T. E., Li, C. I. 2011; 103 (6): 470-477

    Abstract

    Triple-negative (ie, estrogen receptor [ER], progesterone receptor, and HER2 negative) breast cancer occurs disproportionately among African American women compared with white women and is associated with a worse prognosis than ER-positive (ER+) breast cancer. Hormonally mediated risk factors may be differentially related to risk of triple-negative and ER+ breast cancers.Using data from 155,723 women enrolled in the Women's Health Initiative, we assessed associations between reproductive and menstrual history, breastfeeding, oral contraceptive use, and subtype-specific breast cancer risk. We used Cox regression to evaluate associations with triple-negative (N = 307) and ER+ (N = 2610) breast cancers and used partial likelihood methods to test for differences in subtype-specific hazard ratios (HRs).Reproductive history was differentially associated with risk of triple-negative and ER+ breast cancers. Nulliparity was associated with decreased risk of triple-negative breast cancer (HR = 0.61, 95% confidence interval [CI] = 0.37 to 0.97) but increased risk of ER+ breast cancer (HR = 1.35, 95% CI = 1.20 to 1.52). Age-adjusted absolute rates of triple-negative breast cancer were 2.71 and 1.54 per 10,000 person-years in parous and nulliparous women, respectively; by comparison, rates of ER+ breast cancer were 21.10 and 28.16 per 10,000 person-years in the same two groups. Among parous women, the number of births was positively associated with risk of triple-negative disease (HR for three births or more vs one birth = 1.46, 95% CI = 0.82 to 2.63) and inversely associated with risk of ER+ disease (HR = 0.88, 95% CI = 0.74 to 1.04). Ages at menarche and menopause were modestly associated with risk of ER+ but not triple-negative breast cancer; breastfeeding and oral contraceptive use were not associated with either subtype.The association between parity and breast cancer risk differs appreciably for ER+ and triple-negative breast cancers. These findings require further confirmation because the biological mechanisms underlying these differences are uncertain.

    View details for DOI 10.1093/jnci/djr030

    View details for Web of Science ID 000288554900007

    View details for PubMedID 21346227

  • Association of active and passivesmoking with risk of breast cancer among postmenopausal women: a prospective cohort study BRITISH MEDICAL JOURNAL Luo, J., Margolis, K. L., Wactawski-Wende, J., Horn, K., Messina, C., Stefanick, M. L., Tindle, H. A., Tong, E., Rohan, T. E. 2011; 342

    Abstract

    To examine the association between smoking and risk of invasive breast cancer using quantitative measures of lifetime passive and active smoking exposure among postmenopausal women.Prospective cohort study.40 clinical centres in the United States.79,990 women aged 50-79 enrolled in the Women's Health Initiative Observational Study during 1993-8.Self reported active and passive smoking, pathologically confirmed invasive breast cancer.In total, 3520 incident cases of invasive breast cancer were identified during an average of 10.3 years of follow-up. Compared with women who had never smoked, breast cancer risk was elevated by 9% among former smokers (hazard ratio 1.09 (95% CI 1.02 to 1.17)) and by 16% among current smokers (hazard ratio 1.16 (1.00 to 1.34)). Significantly higher breast cancer risk was observed in active smokers with high intensity and duration of smoking, as well as with initiation of smoking in the teenage years. The highest breast cancer risk was found among women who had smoked for ? 50 years or more (hazard ratio 1.35 (1.03 to 1.77) compared with all lifetime non-smokers, hazard ratio 1.45 (1.06 to 1.98) compared with lifetime non-smokers with no exposure to passive smoking). An increased risk of breast cancer persisted for up to 20 years after smoking cessation. Among women who had never smoked, after adjustment for potential confounders, those with the most extensive exposure to passive smoking (? 10 years' exposure in childhood, ? 20 years' exposure as an adult at home, and ? 10 years' exposure as an adult at work) had a 32% excess risk of breast cancer compared with those who had never been exposed to passive smoking (hazard ratio 1.32 (1.04 to 1.67)). However, there was no significant association in the other groups with lower exposure and no clear dose response to cumulative passive smoking exposure.Active smoking was associated with an increase in breast cancer risk among postmenopausal women. There was also a suggestion of an association between passive smoking and increased risk of breast cancer.

    View details for DOI 10.1136/bmj.d1016

    View details for Web of Science ID 000288166600009

    View details for PubMedID 21363864

  • BMI and Fracture Risk in Older Men: The Osteoporotic Fractures in Men Study (MrOS) JOURNAL OF BONE AND MINERAL RESEARCH Nielson, C. M., Marshall, L. M., Adams, A. L., LeBlanc, E. S., Cawthon, P. M., Ensrud, K., Stefanick, M. L., Barrett-Connor, E., Orwoll, E. S. 2011; 26 (3): 496-502

    Abstract

    Low body mass index (BMI) is a risk factor for fracture, but little is known about the association between high BMI and fracture risk. We evaluated the association between BMI and fracture in the Osteoporotic Fractures in Men Study (MrOS), a cohort of 5995 US men 65 years of age and older. Standardized measures included weight, height, and hip bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA); medical history; lifestyle; and physical performance. Only 6 men (0.1%) were underweight (<18.5 kg/m(2)); therefore, men in this category were excluded. Also, 27% of men had normal BMI (18.5 to 24.9 kg/m(2)), 52% were overweight (25 to 29.9 kg/m(2)), 18% were obese I (30 to 34.9 kg/m(2)), and 3% were obese II (35 to 39.9 kg/m(2)). Overall, nonspine fracture incidence was 16.1 per 1000 person-years, and hip fracture incidence was 3.1 per 1000 person-years. In age-, race-, and BMD-adjusted models, compared with normal weight, the hazard ratio (HR) for nonspine fracture was 1.04 [95% confidence interval (CI) 0.87-1.25] for overweight, 1.29 (95% CI 1.00-1.67) for obese I, and 1.94 (95% CI 1.25-3.02) for obese II. Associations were weaker and not statistically significant after adjustment for mobility limitations and walking pace (HR = 1.02, 95% CI 0.84-1.23, for overweight; HR = 1.12, 95% CI 0.86-1.46, for obese I, and HR = 1.44, 95% CI 0.90-2.28, for obese II). Obesity is common among older men, and when BMD is held constant, it is associated with an increased risk of fracture. This association is at least partially explained by worse physical function in obese men.

    View details for DOI 10.1002/jbmr.235

    View details for Web of Science ID 000287827600009

    View details for PubMedID 20814955

  • Physical activity, additional breast cancer events, and mortality among early-stage breast cancer survivors: findings from the WHEL Study CANCER CAUSES & CONTROL Bertram, L. A., Stefanick, M. L., Saquib, N., Natarajan, L., Patterson, R. E., Bardwell, W., Flatt, S. W., Newman, V. A., Rock, C. L., Thomson, C. A., Pierce, J. P. 2011; 22 (3): 427-435

    Abstract

    Research suggests that physical activity is associated with improved breast cancer survival, yet no studies have examined the association between post-diagnosis changes in physical activity and breast cancer outcomes. The aim of this study was to determine whether baseline activity and 1-year change in activity are associated with breast cancer events or mortality.A total of 2,361 post-treatment breast cancer survivors (Stage I-III) enrolled in a randomized controlled trial of dietary change completed physical activity measures at baseline and one year. Physical activity variables (total, moderate-vigorous, and adherence to guidelines) were calculated for each time point. Median follow-up was 7.1 years. Outcomes were invasive breast cancer events and all-cause mortality.Those who were most active at baseline had a 53% lower mortality risk compared to the least active women (HR = 0.47; 95% CI: 0.26, 0.84; p = .01). Adherence to activity guidelines was associated with a 35% lower mortality risk (HR = 0.65, 95% CI: 0.47, 0.91; p < .01). Neither baseline nor 1-year change in activity was associated with additional breast cancer events.Higher baseline (post-treatment) physical activity was associated with improved survival. However, change in activity over the following year was not associated with outcomes. These data suggest that long-term physical activity levels are important for breast cancer prognosis.

    View details for DOI 10.1007/s10552-010-9714-3

    View details for Web of Science ID 000288542400010

    View details for PubMedID 21184262

  • Mortality Risk in Older Men Associated with Changes in Weight, Lean Mass, and Fat Mass JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Lee, C. G., Boyko, E. J., Nielson, C. M., Stefanick, M. L., Bauer, D. C., Hoffman, A., Dam, T. L., Lapidus, J. A., Cawthon, P. M., Ensrud, K. E., Orwoll, E. S. 2011; 59 (2): 233-240

    Abstract

    To evaluate risk of all-cause mortality associated with changes in body weight, total lean mass, and total fat mass in older men.Longitudinal cohort study.Six U.S. clinical centers.Four thousand three hundred thirty-one ambulatory men aged 65 to 93 at baseline.Repeated measurements of body weight and total lean and fat mass were taken using dual-energy X-ray absorptiometry 4.6 ± 0.4 years apart. Percentage changes in these measures were categorized as gain (+5%), loss (-5%), or stable (-5% to +5%). Deaths were verified centrally according to death certificate reviews, and proportional hazard models were used to estimate the risk of mortality.After accounting for baseline lifestyle factors and medical conditions, a higher risk of mortality was found for men with weight loss (hazard rat (HR)=1.84, 95% confidence interval (CI)=1.50-2.26), total lean mass loss (HR=1.78, 95% CI=1.45-2.19), and total fat mass loss (HR=1.72, 95% CI=1.34-2.20) than for men who were stable for each body composition measure. Men with total fat mass gain had a slightly greater mortality risk (HR=1.29, 95% CI=0.99-1.67) than those who remained stable. These associations did not differ according to baseline age, obesity, or self-reported health status (P for interactions >.10), although self-reported weight loss intent altered mortality risks with total fat mass (P for interaction=.04) and total lean mass (P for interaction=.09) change.Older men who lost weight, total lean mass, or total fat mass had a higher risk of mortality than men who remained stable.

    View details for DOI 10.1111/j.1532-5415.2010.03245.x

    View details for Web of Science ID 000287240700006

    View details for PubMedID 21288234

  • Rest/Activity Rhythms and Cardiovascular Disease in Older Men CHRONOBIOLOGY INTERNATIONAL Paudel, M. L., Taylor, B. C., Ancoli-Israel, S., Stone, K. L., Tranah, G., Redline, S., Barrett-Connor, E., Stefanick, M. L., Ensrud, K. E. 2011; 28 (3): 258-266

    Abstract

    Prior studies have suggested an increased risk of cardiovascular disease (CVD)-related mortality in older adults with disturbed circadian rest/activity rhythms (RARs). The objective goal of this study was to examine the association between disrupted RARs and risk of CVD events in older men. A total of 2968 men aged 67 yrs and older wore wrist actigraphs for 115?±?18 consecutive hours. RAR parameters were computed from wrist actigraphy data and expressed as quartiles (Q). CVD events consisted of a composite outcome of coronary heart disease (CHD), stroke, and peripheral vascular disease (PVD) events. Secondary analyses examined associations between RARs and individual components of the composite outcome (CHD, stroke, and PVD). There were 490 CVD events over an average of 4.0?±?1.2 yrs. Overall, reduced amplitude (HR?=?1.31, 95% confidence interval [CI] 1.01-1.71 for Q2 vs. Q4) and greater minimum (HR?=?1.33, 95% CI 1.01-1.73 for Q4 vs. Q1) were associated with an increased risk of CVD events in multivariable-adjusted models. In secondary analyses, there was an independent association between reduced amplitude (HR?=?1.36, 95% CI 1.00-1.86) and greater minimum activity counts (HR?=?1.39, 95% CI 1.02-1.91) with increased risk of CHD events. Reduced F value (HR?=?2.88, 95% CI 1.41-5.87 for Q1 vs. Q4 and HR?=?2.71, 95% CI 1.34-5.48 for Q2 vs. Q4) and later occurring acrophase of the RAR (HR?=?1.65, 95% CI 1.04-2.63 for Q4 vs. Q2-3) were associated with an increased risk of PVD events. Results were similar in men without a history of CVD events. The findings revealed that among older men, measures of decreased circadian activity rhythm robustness (reduced amplitude and greater minimum activity) were associated with an increased risk of CVD events, primarily through increased risk of CHD or stroke events, whereas measures of reduced circadian activity rhythmicity were not associated with risk of CVD events overall, but were associated with an increased risk of PVD events. These results should be confirmed in other populations.

    View details for DOI 10.3109/07420528.2011.553016

    View details for Web of Science ID 000289000900008

    View details for PubMedID 21452921

  • Circulating 25-Hydroxyvitamin D Levels and Frailty in Older Men: The Osteoporotic Fractures in Men Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Ensrud, K. E., Blackwell, T. L., Cauley, J. A., Cummings, S. R., Barrett-Connor, E., Dam, T. L., Hoffman, A. R., Shikany, J. M., Lane, N. E., Stefanick, M. L., Orwoll, E. S., Cawthon, P. M. 2011; 59 (1): 101-106

    Abstract

    To determine the cross-sectional and longitudinal associations between 25-hydroxyvitamin D (25(OH)D) levels and frailty status in older men.Prospective cohort study.Six U.S. community-based centers.One thousand six hundred six men aged 65 and older.25(OH)D (liquid chromatography tandem mass spectroscopy) and frailty status (criteria similar to those used in the Cardiovascular Health Study) measured at baseline; frailty status assessment repeated an average of 4.6 years later. Frailty status was classified as robust, intermediate, or frail at baseline and robust, intermediate, frail, or dead at follow-up.After adjusting for multiple potential confounders, men with 25(OH)D levels less than 20.0 ng/mL had 1.5 times higher odds (multivariate odds ratio (MOR)=1.47, 95% confidence interval (CI)=1.07-2.02) of greater frailty status at baseline than men with 25(OH)D levels of 30.0 ng/mL or greater (referent group), whereas frailty status was similar in men with 25(OH)D levels from 20.0 to 29.9 ng/mL and those with levels of 30.0 ng/mL or greater (MOR=1.02, 95% CI=0.78-1.32). However, in 1,267 men not classified as frail at baseline, there was no association between lower baseline 25(OH)D level and odds of greater frailty status at the 4.6-year follow-up. Findings were the same when 25(OH)D was expressed in quartiles or as a continuous variable.Lower levels of 25(OH)D (<20.0 ng/mL) in community-dwelling older men were independently associated with greater evidence of frailty at baseline but did not predict greater risk of greater frailty status at 4.6 years.

    View details for DOI 10.1111/j.1532-5415.2010.03201.x

    View details for Web of Science ID 000286208200015

    View details for PubMedID 21226680

  • Recreational physical activity, anthropometric factors, and risk of ductal carcinoma in situ of the breast in a cohort of postmenopausal women CANCER CAUSES & CONTROL Kabat, G. C., Kim, M., Wactawski-Wende, J., Lane, D., Adams-Campbell, L. L., Gaudet, M., Stefanick, M. L., Vitolins, M., Chlebowski, R. T., Wassertheil-Smoller, S., Rohan, T. E. 2010; 21 (12): 2173-2181

    Abstract

    To assess the association of recreational physical activity and anthropometric factors in relation to risk of ductal carcinoma in situ (DCIS) of the breast.The association was examined in a cohort of 58,055 postmenopausal women participating in the Women's Health Initiative (WHI) clinical trials, among whom 450 cases of DCIS were ascertained after a median follow-up of 8.0 years. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI).After adjustment for covariates, the hazard ratio for DCIS among women with ? 20 metabolic equivalent task-hours per week (MET-h/week) of total recreational physical activity compared to women who did not engage in any recreational physical activity (0 MET-h/week) was 0.97 (95% CI 0.70-1.34). Neither body mass index nor waist circumference was associated with risk. In addition, physical activity and anthropometric factors were not associated with risk of either high-grade or low-/moderate-grade DCIS.Recreational physical activity and anthropometric factors showed no association with risk of DCIS in postmenopausal women in the WHI clinical trial.

    View details for DOI 10.1007/s10552-010-9637-z

    View details for Web of Science ID 000288609600025

    View details for PubMedID 20814736

  • Sex differences in the prevalence of peripheral artery disease in patients undergoing coronary catheterization VASCULAR MEDICINE Rafie, A. H., Stefanick, M. L., Sims, S. T., Phan, T., Higgins, M., Gabriel, A., Assimes, T., Narasimhan, B., Nead, K. T., Myers, J., Olin, J., Cooke, J. P. 2010; 15 (6): 443-450

    Abstract

    To determine whether there are sex differences in the prevalence of peripheral artery disease, we performed an observational study of 1014 men and 547 women, aged ? 40 years, referred for elective coronary angiography. Women were slightly older, more obese, had higher low-density lipoprotein cholesterol (LDL-C) levels and systolic blood pressure (BP), and were more likely to be African American. Women had higher high-density lipoprotein cholesterol (HDL-C) levels, lower diastolic BP, and were less likely to smoke or to have a history of cardiovascular disease. Women had less prevalent (62% vs 81%) and less severe coronary artery disease (CAD) (p < 0.001 for both) by coronary angiography, but more prevalent peripheral artery disease (PAD) as determined by the ankle-brachial index (ABI) than men (23.6% versus 17.2%). Independent predictors of lower ABI were female sex, black race, older age, tobacco use, CAD, diabetes, and triglyceride level. In a full multivariable logistic regression model, women had a risk-adjusted odds ratio for PAD of 1.78 (95% CI 1.25-2.54) relative to men. Among patients referred for coronary angiography, women have less prevalent and less severe CAD, but more prevalent PAD, a sex difference that is not explained by traditional cardiovascular disease risk factors or CAD severity. Clinical Trial Registration-URL: http://clinicaltrials.gov. Unique identifier: NCT00380185.

    View details for DOI 10.1177/1358863X10388345

    View details for Web of Science ID 000285574400002

    View details for PubMedID 21183651

  • Vasomotor symptoms and coronary artery calcium in postmenopausal women MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Allison, M. A., Manson, J. E., Aragaki, A., Langer, R. D., Rossouw, J., Curb, D., Martin, L. W., Phillips, L., Stefanick, M. L., Cochrane, B. B., Sarto, G., Barnhart, J., O'Sullivan, M. J., Johnson, K. C., Gass, M., Trevisan, M., Woods, N. F. 2010; 17 (6): 1136-1145

    Abstract

    We assessed whether vasomotor symptoms (VMS) are associated with coronary artery calcium (CAC) and how hormone therapy (HT) may influence this association.Participants were a subset of women aged 50 to 59 years with a history of hysterectomy who were enrolled in the Women's Health Initiative (WHI) estrogen-alone clinical trial and underwent a CT scan of the chest at the end of the trial to determine CAC. Participants provided information about VMS (hot flashes and/or night sweats), as well as HT use, on self-administered questionnaires at trial baseline.The sample consisted of 918 women with a mean (SD) age of 55.1 (2.8) years at WHI randomization and 64.8 (2.9) years at CAC ascertainment. The prevalence of a CAC score higher than 0 was 46%, whereas the prevalence of a CAC score of 10 or higher and higher than 100 was 39% and 19%, respectively. At randomization, 77% reported a history of any VMS at any time before or at enrollment in the WHI, whereas 20% reported any VMS present only at enrollment. Compared with those without a history of any VMS and after adjustment for potential confounders, a history of any VMS at any time up to and including WHI enrollment was associated with significantly reduced odds for CAC higher than 0 (odds ratio, 0.66; 95% CI, 0.45-0.98). Moreover, as duration of HT increased, the inverse association between any VMS and CAC moved toward the null.A history of any VMS was significantly associated with reduced odds for CAC independent of traditional cardiovascular disease risk factors and other relevant covariates. This association seems to be influenced by duration of HT.

    View details for DOI 10.1097/gme.0b013e3181e664dc

    View details for Web of Science ID 000283993700011

    View details for PubMedID 20651617

  • Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in Postmenopausal Women JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Chlebowski, R. T., Anderson, G. L., Gass, M., Lane, D. S., Aragaki, A. K., Kuller, L. H., Manson, J. E., Stefanick, M. L., Ockene, J., Sarto, G. E., Johnson, K. C., Wactawski-Wende, J., Ravdin, P. M., Schenken, R., Hendrix, S. L., Rajkovic, A., Rohan, T. E., Yasmeen, S., Prentice, R. L. 2010; 304 (15): 1684-1692

    Abstract

    In the Women's Health Initiative randomized, placebo-controlled trial of estrogen plus progestin, after a mean intervention time of 5.6 (SD, 1.3) years (range, 3.7-8.6 years) and a mean follow-up of 7.9 (SD, 1.4) years, breast cancer incidence was increased among women who received combined hormone therapy. Breast cancer mortality among participants in the trial has not been previously reported.To determine the effects of therapy with estrogen plus progestin on cumulative breast cancer incidence and mortality after a total mean follow-up of 11.0 (SD, 2.7) years, through August 14, 2009.A total of 16,608 postmenopausal women aged 50 to 79 years with no prior hysterectomy from 40 US clinical centers were randomly assigned to receive combined conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo pill. After the original trial completion date (March 31, 2005), reconsent was required for continued follow-up for breast cancer incidence and was obtained from 12,788 (83%) of the surviving participants.Invasive breast cancer incidence and breast cancer mortality.In intention-to-treat analyses including all randomized participants and censoring those not consenting to additional follow-up on March 31, 2005, estrogen plus progestin was associated with more invasive breast cancers compared with placebo (385 cases [0.42% per year] vs 293 cases [0.34% per year]; hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.07-1.46; P = .004). Breast cancers in the estrogen-plus-progestin group were similar in histology and grade to breast cancers in the placebo group but were more likely to be node-positive (81 [23.7%] vs 43 [16.2%], respectively; HR, 1.78; 95% CI, 1.23-2.58; P = .03). There were more deaths directly attributed to breast cancer (25 deaths [0.03% per year] vs 12 deaths [0.01% per year]; HR, 1.96; 95% CI, 1.00-4.04; P = .049) as well as more deaths from all causes occurring after a breast cancer diagnosis (51 deaths [0.05% per year] vs 31 deaths [0.03% per year]; HR, 1.57; 95% CI, 1.01-2.48; P = .045) among women who received estrogen plus progestin compared with women in the placebo group.Estrogen plus progestin was associated with greater breast cancer incidence, and the cancers are more commonly node-positive. Breast cancer mortality also appears to be increased with combined use of estrogen plus progestin.clinicaltrials.gov Identifier: NCT00000611.

    View details for Web of Science ID 000283129700022

    View details for PubMedID 20959578

  • Gendered Innovations: A New Approach for Nursing Science BIOLOGICAL RESEARCH FOR NURSING Sims, S. T., Stefanick, M. L., Kronenberg, F., Sachedina, N. A., Schiebinger, L. 2010; 12 (2): 156-161

    Abstract

    Considerable sex and gender bias has been recognized within the field of medicine. Investigators have used sex and gender analysis to reevaluate studies and outcomes and generate new perspectives and new questions regarding differential diagnoses and treatments of men and women. Sex and gender analysis acts as an experimental control to provide critical scientific rigor; researchers who ignore it risk ignoring a possible source of error in past, current, and future science. In this article, the authors introduce some tools of sex and gender analysis and illustrate the concept of gendered innovations by demonstrating through examples how this type of analysis has profoundly enhanced human knowledge in health and disease. The authors also provide recommendations for incorporating the concepts of sex and gender analysis into nursing education and research.

    View details for DOI 10.1177/1099800410375108

    View details for Web of Science ID 000281796300006

    View details for PubMedID 20798156

  • Evidence for Geographical and Racial Variation in Serum Sex Steroid Levels in Older Men JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Orwoll, E. S., Nielson, C. M., Labrie, F., Barrett-Connor, E., Cauley, J. A., Cummings, S. R., Ensrud, K., Karlsson, M., Lau, E., Leung, P. C., Lunggren, O., Mellstrom, D., Patrick, A. L., Stefanick, M. L., Nakamura, K., Yoshimura, N., Zmuda, J., Vandenput, L., Ohlsson, C. 2010; 95 (10): E151-E160

    Abstract

    Despite considerable racial and geographical differences in human phenotypes and in the incidence of diseases that may be associated with sex steroid action, there are few data concerning variation in sex steroid levels among populations. We designed an international study to determine the degree to which geography and race influence sex steroid levels in older men.Using mass spectrometry, concentrations of serum androgens, estrogens, and sex steroid precursors/metabolites were measured in 5003 older men from five countries. SHBG levels were assessed using radioimmunoassay.There was substantial geographical variation in the levels of sex steroids, precursors, and metabolites, as well as SHBG. For instance, Asian men in Hong Kong and Japan, but not in the United States, had levels of total testosterone approximately 20% higher than in other groups. Even greater variation was present in levels of estradiol, SHBG, and dihydrotestosterone. Group differences in body mass index did not explain most geographical differences. In addition, body mass index-independent racial differences were present; Black men had higher levels of estrogens (estradiol, estrone), and Asian men had lower levels of glucuronidated androgen metabolites.On a global scale, there are important geographical and racial differences in the concentrations of serum sex steroids and SHBG in older men.

    View details for DOI 10.1210/jc.2009-2435

    View details for Web of Science ID 000282573300041

    View details for PubMedID 20668046

  • Menopausal symptom experience before and after stopping estrogen therapy in the Women's Health Initiative randomized, placebo-controlled trial MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Brunner, R. L., Aragaki, A., Barnabei, V., Cochrane, B. B., Gass, M., Hendrix, S., Lane, D., Ockene, J., Woods, N. F., Yasmeen, S., Stefanick, M. 2010; 17 (5): 946-954

    Abstract

    The aim of this study was to assess vasomotor and other menopausal symptoms before starting estrogens or placebo, 1 year later, again at trial closure, and after stopping estrogens or placebo. The role of baseline symptoms and age was examined, as was the frequency and determinants of hormone use and symptom management strategies after discontinuing conjugated equine estrogens (CEE) or placebo.Intent-to-treat analyses of 10,739 postmenopausal women before and 1 year after randomization to CEE or placebo at 40 clinical centers and a cohort analysis of participants (n = 3,496) who continued taking assigned study pills up to trial closure and completed symptom surveys shortly before (mean, 7.4 +/- 1.1 y from baseline) and after (mean, 306 +/- 55 d after trial closure) stopping pills were performed. Generalized linear regression modeled vasomotor symptoms, vaginal dryness, breast tenderness, pain/stiffness, and mood swings as a function of treatment assignment and baseline symptoms, before and after stopping study pills.Approximately one third of participants reported at least one moderate to severe symptom at baseline. Fewer symptoms were reported with increasing age, except joint pain/stiffness, which was similar among age groups. At 1 year, hot flashes, night sweats, and vaginal dryness were reduced by CEE, whereas breast tenderness was increased. Breast tenderness was also significantly higher in the CEE group at trial closure. After stopping, vasomotor symptoms were reported by significantly more women who had reported symptoms at baseline, compared with those who had not, and by significantly more participants assigned to CEE (9.8%) versus placebo (3.2%); however, among women with no moderate or severe symptoms at baseline, more than five times as many reported hot flashes after stopping CEE (7.2%) versus placebo (1.5%).CEE significantly reduced vasomotor symptoms and vaginal dryness in women with baseline symptoms but increased breast tenderness. The likelihood of experiencing symptoms was significantly higher after stopping CEE than placebo regardless of baseline symptom status. These potential effects should be considered before initiating CEE to relieve menopausal symptoms.

    View details for DOI 10.1097/gme.0b013e3181d76953

    View details for Web of Science ID 000281614700013

    View details for PubMedID 20505547

  • Lung Cancer Among Postmenopausal Women Treated With Estrogen Alone in the Women's Health Initiative Randomized Trial JOURNAL OF THE NATIONAL CANCER INSTITUTE Chlebowski, R. T., Anderson, G. L., Manson, J. E., Schwartz, A. G., Wakelee, H., Gass, M., Rodabough, R. J., Johnson, K. C., Wactawski-Wende, J., Kotchen, J. M., Ockene, J. K., O'Sullivan, M. J., Hubbell, F. A., Chien, J. W., Chen, C., Stefanick, M. L. 2010; 102 (18): 1413-1421

    Abstract

    In the Women's Health Initiative (WHI) randomized controlled trial, use of estrogen plus progestin increased lung cancer mortality. We conducted post hoc analyses in the WHI trial evaluating estrogen alone to determine whether use of conjugated equine estrogen without progestin had a similar adverse influence on lung cancer.The WHI study is a randomized, double-blind, placebo-controlled trial conducted in 40 centers in the United States. A total of 10?739 postmenopausal women aged 50-79 years who had a previous hysterectomy were randomly assigned to receive a once-daily 0.625-mg tablet of conjugated equine estrogen (n = 5310) or matching placebo (n = 5429). Incidence and mortality rates for all lung cancers, small cell lung cancers, and non-small cell lung cancers in the two randomization groups were compared by use of hazard ratios (HRs) and 95% confidence intervals (CIs) that were estimated from Cox proportional hazards regression analyses. Analyses were by intention to treat, and all statistical tests were two-sided.After a mean of 7.9 years (standard deviation = 1.8 years) of follow-up, 61 women in the hormone therapy group were diagnosed with lung cancer compared with 54 in the placebo group (incidence of lung cancer per year = 0.15% vs 0.13%, respectively; HR of incidence = 1.17, 95% CI = 0.81 to 1.69, P = .39). Non-small cell lung cancers were of comparable number, stage, and grade in both groups. Deaths from lung cancer did not differ between the two groups (34 vs 33 deaths in estrogen and placebo groups, respectively; HR of death = 1.07, 95% CI = 0.66 to 1.72, P = .79).Unlike use of estrogen plus progestin, which increased deaths from lung cancer, use of conjugated equine estrogen alone did not increase incidence or death from lung cancer.

    View details for DOI 10.1093/jnci/djq285

    View details for Web of Science ID 000282176600010

    View details for PubMedID 20709992

  • Alcohol Consumption and Risk of Ductal Carcinoma In situ of the Breast in a Cohort of Postmenopausal Women CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Kabat, G. C., Kim, M., Shikany, J. M., Rodgers, A. K., Wactawski-Wende, J., Lane, D., Powell, L., Stefanick, M. L., Freiberg, M. S., Kazlauskaite, R., Chlebowski, R. T., Wassertheil-Smoller, S., Rohan, T. E. 2010; 19 (8): 2066-2072

    Abstract

    Observational studies have commonly linked higher alcohol consumption with a modest increase in invasive breast cancer risk, but cohort studies have not examined alcohol intake in relation to ductal carcinoma in situ (DCIS).The association between adulthood alcohol consumption assessed at baseline and subsequent DCIS risk was examined in a cohort of postmenopausal women participating in the Women's Health Initiative clinical trials, in which mammography was protocol-mandated. Alcohol intake was assessed by a semiquantitative food-frequency questionnaire. Reported DCIS cases were verified by central pathology report review. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals.The cohort consisted of 63,822 women with information on alcohol intake, among whom 489 cases of DCIS were ascertained after a median follow-up of 8.0 years. For the primary analysis, invasive breast cancer was treated as a competing risk, and follow-up time was censored at the date of diagnosis of invasive breast cancer. After adjustment for covariates, the hazard ratio for DCIS among women who consumed 14 or more servings of alcohol per week, relative to nondrinkers, was 0.87 (95% confidence interval, 0.50-1.51). In addition, alcohol intake was not associated with risk of either high-grade or low-/moderate-grade DCIS.In this large cohort study of postmenopausal women, alcohol consumption was not associated with risk of DCIS.If other studies confirm our findings, this would suggest that alcohol may have an effect later in the carcinogenic process.

    View details for DOI 10.1158/1055-9965.EPI-10-0388

    View details for Web of Science ID 000280675000020

    View details for PubMedID 20647412

  • Bone mineral density and prevalent osteoarthritis of the hip in older men for the Osteoporotic Fractures in Men (MrOS) Study Group OSTEOPOROSIS INTERNATIONAL Chaganti, R. K., Parimi, N., Lang, T., Orwoll, E., Stefanick, M. L., Nevitt, M., Lane, N. E. 2010; 21 (8): 1307-1316

    Abstract

    We evaluated the association of bone mineral density (BMD) and osteoarthritis (OA) of the hip in elderly men. We found that elderly men with moderate to severe radiographic hip OA (RHOA) had significantly higher areal BMD (aBMD) and volumetric BMD (vBMD) at both the lumbar spine and hip compared to age similar controls without OA.We evaluated the association of BMD measured by dual energy X-ray absorptiometry (DXA) and quantitative computerized tomography (integral, cortical, and trabecular vBMD) and RHOA in a cohort of elderly men.A cross-sectional analysis was conducted within the Study of Osteoporotic Fractures in Men, a prospective cohort study of 5,995 US men age > or = 65 years. Standing pelvic x-rays were done in 4,024 subjects and scored for prevalent RHOA severity. DXA was done in 3,886 subjects, and aBMD and vBMD associations were compared with RHOA score using linear regression, adjusting for covariates.Both moderate and severe RHOA groups had significantly higher aBMD at all BMD sites (range, 3.7-10.0% difference; p value 0.0012 and p value < 0.005) compared to the control group with no RHOA. The difference remained strong after adjusting for covariates. While the total hip and lumbar spine cortical vBMD measurements of subjects with moderate or severe RHOA was increased compared to controls, trabecular vBMD was not.Older men, with both moderate and severe RHOA, had significantly higher aBMD and integral vBMD at the hip and lumbar spine compared to controls without RHOA.

    View details for DOI 10.1007/s00198-009-1105-9

    View details for Web of Science ID 000279478500003

    View details for PubMedID 20101493

  • Postmenopausal hormone therapy and cardiovascular disease in women NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES Stefanick, M. L. 2010; 20 (6): 451-458

    Abstract

    The belief in the hypothesis of cardiovascular benefit of hormone therapy (HT) in postmenopausal women was widespread; however, the Women's Health Initiative (WHI) hormone trials found no evidence of coronary heart disease (CHD) benefit among women aged 50-79 with no prior CHD diagnosis and HT increased risk of stroke. This article reviews the literature regarding HT and CHD, with emphasis on the findings from the WHI trials.Findings from observational studies and animal studies addressing biological plausibility that had been interpreted as evidence to support the use of HT were reviewed and findings from the trials of women with cardiovascular disease and the WHI hormone trials are summarized, with specific commentary on the issue of differential effects of HT in younger versus older women.HT should not be prescribed for the purpose of preventing cardiovascular disease. The WHI offered support for the current U.S. Food and Drug Administration recommendation to limit HT to short-term use. There is a clear need for a greater understanding of the effects of both endogenous and exogenous estrogens in relationship to the aging cardiovascular system.

    View details for DOI 10.1016/j.numecd.2010.02.015

    View details for Web of Science ID 000281612200011

    View details for PubMedID 20554177

  • Estrogen Alone in Postmenopausal Women and Breast Cancer Detection by Means of Mammography and Breast Biopsy JOURNAL OF CLINICAL ONCOLOGY Chlebowski, R. T., Anderson, G., Manson, J. E., Pettinger, M., Yasmeen, S., Lane, D., Langer, R. D., Hubbell, F. A., McTiernan, A., Hendrix, S., Schenken, R., Stefanick, M. L. 2010; 28 (16): 2690-2697

    Abstract

    As the influence of estrogen alone on breast cancer detection is not established, we examined this issue in the Women's Health Initiative trial, which randomly assigned 10,739 postmenopausal women with prior hysterectomy to conjugated equine estrogen (CEE; 0.625 mg/d) or placebo.Screening mammography and breast exams were performed at baseline and annually. Breast biopsies were based on clinical findings. Effects of CEE alone on breast cancer detection were determined by using receiver operating characteristic (ROC) analyses of mammogram performance.After a 7.1-year mean follow-up, fewer invasive breast cancers were diagnosed in the CEE than in the placebo group, but the difference was not statistically significant. Use of CEE alone increased mammograms with short-interval follow-up recommendations (cumulative, 39.2% v 29.6.3%; P < .001) but not abnormal mammograms (ie, those suggestive of or highly suggestive of malignancy; cumulative, 7.3% v 7.0%; P = .41). Breast biopsies were more frequent in the CEE group (cumulative, 12.5% v 10.7%; P = .004) and less commonly diagnosed as cancer (8.9% v 15.8%, respectively, with positive biopsies; P = .04). Mammographic breast cancer detection in the CEE group was significantly compromised only in the early years of use.CEE alone use for 5 years results in approximately one in 11 and one in 50 women having otherwise avoidable mammograms with short-interval follow-up recommendations or breast biopsies, respectively. Although the breast biopsies on CEE were less commonly diagnosed as cancer, breast cancer detection was not substantially compromised. These findings differ from estrogen-plus-progestin use, for which significantly increased abnormal mammograms and a compromise in breast cancer detection are seen.

    View details for DOI 10.1200/JCO.2009.24.8799

    View details for Web of Science ID 000278108800007

    View details for PubMedID 20439627

  • Physical Activity Resources and Changes in Walking in a Cohort of Older Men AMERICAN JOURNAL OF PUBLIC HEALTH Michael, Y. L., Perdue, L. A., Orwoll, E. S., Stefanick, M. L., Marshall, L. M. 2010; 100 (4): 654-660

    Abstract

    We evaluated the influence of physical activity resources and neighborhood-level socioeconomic status (SES) on walking among community-dwelling older men.Participants reported time walked per day at baseline (2000-2002) and follow-up. Residential addresses were linked to a geographic information system database to assess proximity to parks, trails, and recreational facilities. Log-binomial regression analyses were conducted to test the hypothesis that men living near physical activity resources were more likely to increase or maintain time walked.Average time walked per day declined by 6 minutes between baseline and follow-up (P < .05). There was a significant interaction of neighborhood SES and physical activity with walking time (P < .1). Proximity to parks and proximity to trails, respectively, were associated with a 22% (95% confidence interval [CI] = 1.01, 1.47) and 34% (95% CI = 1.16, 1.55) higher likelihood of maintaining or increasing walking time in high-SES neighborhoods, but there was no association in low-SES neighborhoods. Proximity to recreational facilities was not associated with walking.Uncovering reasons that proximity to parks and trails is not associated with maintenance of walking activity among men in low-SES neighborhoods could provide new insight into ways to promote physical activity.

    View details for DOI 10.2105/AJPH.2009.172031

    View details for Web of Science ID 000275937200017

    View details for PubMedID 20167887

  • Association between sex steroids and cognition in elderly men CLINICAL ENDOCRINOLOGY LeBlanc, E. S., Wang, P. Y., Janowsky, J. S., Neiss, M. B., Fink, H. A., Yaffe, K., Marshall, L. M., Lapidus, J. A., Stefanick, M. L., Orwoll, E. S. 2010; 72 (3): 393-403

    Abstract

    To examine the association of cognitive function with sex steroid and sex hormone binding globulin (SHBG) levels among elderly men.Prospective cohort study, The Osteoporotic Fractures in Men Study (MrOS), consisting of 5995 US community dwelling men of 65 years or older.One thousand six hundred and two men were chosen randomly from MrOS cohort for sex steroid level measurements by Mass Spectrometry (MS) at baseline. Two thousand six hundred and twenty-three MrOS participants with sex steroids measured using RIA were also examined.Baseline and follow-up (4.5 years later) performance on two cognitive tests: Trails B (executive function and motor speed) and 3MS (global cognitive function). Baseline total testosterone and oestradiol were measured by MS. Free testosterone (free-T) and free oestradiol (free-E) were calculated. SHBG was measured by radioimmunoassay. Data were analysed using linear regression.Baseline free-T and free-E levels were not associated with cognitive performance or change in cognition, following adjustment for age, education, race, health status and alcohol use. Baseline SHBG levels were inversely associated with follow-up trails B (P = 0.03) and 3MS performance (P = 0.02). Higher SHBG was associated with an increased risk of cognitive decline. Total sex steroid levels were not associated with cognitive performance.Despite large numbers of participants and rigorous sex steroid measurements, we did not observe an association between cognition and either testosterone or oestradiol levels. We conclude that endogenous sex steroids in the normal range are not related to executive function or global cognitive function in elderly men. High SHBG deserves further examination as a risk factor for cognitive decline.

    View details for DOI 10.1111/j.1365-2265.2009.03692.x

    View details for Web of Science ID 000274438600017

    View details for PubMedID 19744108

  • Relative Effects of Tamoxifen, Raloxifene, and Conjugated Equine Estrogens on Cognition JOURNAL OF WOMENS HEALTH Espeland, M. A., Shumaker, S. A., Limacher, M., Rapp, S. R., Bevers, T. B., Barad, D. H., Coker, L. H., Gaussoin, S. A., Stefanick, M. L., Lane, D. S., Maki, P. M., Resnick, S. M. 2010; 19 (3): 371-379

    Abstract

    To compare the relative effects of conjugated equine estrogens (CEE), raloxifene, and tamoxifen therapies on cognition among women aged > or =65 years.Annual Modified Mini-Mental State (3MS) examinations were used to assess global cognitive function in the two randomized placebo-controlled clinical trials of CEE therapies of the Women's Health Initiative Memory Study (WHIMS) and the Cognition in the Study of Tamoxifen and Raloxifene (CoSTAR). Analyses were limited to women who had 3MS testing at baseline and the first 3 years of follow-up and, because of potential ethnic-related differences between studies, to Caucasian women (WHIMS n = 6211, CoSTAR n = 250). Covariate adjustment was used to compare the postrandomization mean 3MS scores among the three active therapies with placebo therapy while controlling for differences between groups with respect to dementia risk factors.At baseline, the average (SD) 3MS scores by group were 95.24 (4.28) for placebo, 95.19 (4.33) for CEE, 94.60 (4.76) for raloxifene, and 95.02 (4.03) for tamoxifen. Compared with placebo, each active therapy was associated with a small mean relative deficit in 3MS scores of < or =0.5 units, which was fairly consistent between women with and without prior hysterectomy. Relative deficits were slightly greater for tamoxifen (p = 0.001) and less marked for raloxifene (p = 0.06) and CEE (p = 0.02) therapies. Relative deficits appeared to be greater among women with lower baseline 3MS scores: p = 0.009 (tamoxifen), p = 0.08 (raloxifene), and p = 0.03 (CEE).Although unmeasured differences between trials may have confounded analyses, these findings raise the possibility that both tamoxifen and raloxifene adversely affect cognitive function in older women; however, the magnitude of the effect is small, and the long-term consequences are unknown.

    View details for DOI 10.1089/jwh.2009.1605

    View details for Web of Science ID 000275983200002

    View details for PubMedID 20136553

  • The Relationship Between Cognitive Function and Physical Performance in Older Women: Results From the Women's Health Initiative Memory Study JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Atkinson, H. H., Rapp, S. R., Williamson, J. D., Lovato, J., Absher, J. R., Gass, M., Henderson, V. W., Johnson, K. C., Kostis, J. B., Sink, K. M., Mouton, C. P., Ockene, J. K., Stefanick, M. L., Lane, D. S., Espeland, M. A. 2010; 65 (3): 300-306

    Abstract

    Cognitive function and physical performance are associated, but the common sequence of cognitive and physical decline remains unclear.In the Women's Health Initiative Memory Study (WHIMS) clinical trial, we examined associations at baseline and over a 6-year follow-up period between the Modified Mini-Mental State (3MS) Examination and three physical performance measures (PPMs): gait speed (meters/second), chair stands (number of stands in 15 seconds), and grip strength (kilograms). Using mixed models, we examined the baseline 3MS as predictor of change in PPM, change in the 3MS as predictor of change in PPM, and baseline PPM as predictors of 3MS change.Among 1,793 women (mean age = 70.3 years, 89% white, and mean 3MS score = 95.1), PPM were weakly correlated with 3MS-gait speed: r = .06, p = .02; chair stands: r = .09, p < .001; and grip strength: r = .10, p < .001. Baseline 3MS score was associated with subsequent PPM decline after adjustment for demographics, comorbid conditions, medications, and lifestyle factors. For every SD (4.2 points) higher 3MS score, 0.04 SD (0.04 m/s) less gait speed and 0.05 SD (0.29 kg) less grip strength decline is expected over 6 years (p

    View details for DOI 10.1093/gerona/glp149

    View details for Web of Science ID 000275420800014

    View details for PubMedID 19789197

  • Migraine History and Breast Cancer Risk Among Postmenopausal Women JOURNAL OF CLINICAL ONCOLOGY Li, C. I., Mathes, R. W., Bluhm, E. C., Caan, B., Cavanagh, M. F., Chlebowski, R. T., Michael, Y., O'Sullivan, M. J., Stefanick, M. L., Prentice, R. 2010; 28 (6): 1005-1010

    Abstract

    PURPOSE Both migraine and breast cancer are hormonally mediated. Two recent reports indicate that women with a migraine history may have a lower risk of postmenopausal breast cancer than those who never suffered migraines. This finding requires confirmation; in particular, an assessment of the influence of use of nonsteroidal anti-inflammatory drugs (NSAID) is needed, because many studies indicate that NSAID use also may confer a reduction in breast cancer risk. METHODS We assessed the relationship between self-reported history of migraine and incidence of postmenopausal breast cancer in 91,116 women enrolled on the Women's Health Initiative Observational Study prospective cohort from 1993 to 1998 at ages 50 to 79 years. Through September 15, 2005, there were 4,006 eligible patients with breast cancer diagnosed. Results Women with a history of migraine had a lower risk of breast cancer (hazard ratio [HR], 0.89; 95% CI, 0.80 to 98) than women without a migraine history. This risk did not vary by recent NSAID use. The lower risk was somewhat more pronounced for invasive estrogen-receptor-positive and progesterone-receptor-positive tumors (HR, 0.83; 95% CI, 0.71 to 0.97), as no reduction in risk was observed for invasive ER-negative/PR-negative tumors (HR, 1.16; 95% CI, 0.86 to 1.57), and this difference in risk estimates was borderline statistically significant (P = .06). CONCLUSION This study supports the hypothesis that a history of migraine is associated with a lower risk of breast cancer and that this relationship is independent of recent NSAID use.

    View details for DOI 10.1200/JCO.2009.25.0423

    View details for Web of Science ID 000274653200018

    View details for PubMedID 20100960

  • Changes in C-reactive protein from low-fat diet and/or physical activity in men and women with and without metabolic syndrome METABOLISM-CLINICAL AND EXPERIMENTAL Camhi, S. M., Stefanick, M. L., Ridker, P. M., Young, D. R. 2010; 59 (1): 54-61

    Abstract

    Change in high-sensitivity C-reactive protein (CRP) from low-fat diet (diet) and physical activity (PA) interventions is relatively unknown for adults with metabolic syndrome. The objective of the study was to assess CRP change (DeltaCRP) with diet and/or PA in men and women with and without metabolic syndrome. Men (n = 149) and postmenopausal women (n = 125) with elevated low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol were recruited into a 1-year randomized controlled trial. Treatment groups were as follows: control, diet (reduced total fat, saturated fat, and cholesterol intake), PA (45-60 minutes at 60%-85% maximum heart rate), or diet + PA. Weight loss was not an intervention focus. Metabolic syndrome was defined using the American Heart Association/National Heart, Lung, and Blood Institute criteria. Stored plasma samples were analyzed for CRP. Change in CRP was compared between treatments, within sex and metabolic syndrome status, using analysis of covariance, including covariates for baseline CRP and body fat change. For women with metabolic syndrome (n = 39), DeltaCRP was greater in diet vs control (-1.2 +/- 0.4, P = .009), diet + PA vs control (-1.3 +/- 0.4, P = .006), and diet + PA vs PA (-1.1 +/- 0.4, P = .02). Women with metabolic syndrome receiving the diet component (diet or diet + PA) had greater DeltaCRP compared with those who did not (control or PA) (P = .001). Change in CRP was not significantly different between intervention groups in men overall, women overall, men with (n = 47) or without metabolic syndrome (n = 102), or women without metabolic syndrome (n = 86). Low-fat diet may be the most effective treatment for reducing CRP in women with metabolic syndrome.

    View details for DOI 10.1016/j.metabol.2009.07.008

    View details for Web of Science ID 000276761500009

    View details for PubMedID 19709693

  • Family history of later-onset breast cancer, breast healthy behavior and invasive breast cancer among postmenopausal women: a cohort study BREAST CANCER RESEARCH Gramling, R., Lash, T. L., Rothman, K. J., Cabral, H. J., Silliman, R., Roberts, M., Stefanick, M. L., Harrigan, R., Bertoia, M. L., Eaton, C. B. 2010; 12 (5)

    Abstract

    A family history of later-onset breast cancer (FHLBC) may suggest multi-factorial inheritance of breast cancer risk, including unhealthy lifestyle behaviors that may be shared within families. We assessed whether adherence to lifestyle behaviors recommended for breast cancer prevention--including maintaining a healthful body weight, being physically active and limiting alcohol intake--modifies breast cancer risk attributed to FHLBC in postmenopausal women.Breast cancer outcomes through August 2003 were analyzed in relationship to lifestyle and risk factors collected by questionnaire during enrollment (between 1993 and 1998) of 85,644 postmenopausal women into the Women's Health Initiative Observational Study.During a mean follow-up of 5.4 years, 1997 women were diagnosed with invasive breast cancer. The rate of invasive breast cancer among women with an FHLBC who participated in all three behaviors was 5.94 per 1,000 woman-years, compared with 6.97 per 1,000 woman-years among women who participated in none of the behaviors. The rate among women with no FHLBC who participated in all three behavioral conditions was 3.51 per 1,000 woman-years compared to 4.67 per 1,000 woman-years for those who participated in none. We did not observe a clinically important departure from additive effects (Interaction Contrast: 0.00014; 95% CI: -0.00359, 0.00388).Participating in breast healthy behaviours was beneficial to postmenopausal women and the degree of this benefit was the same for women with and without an FHLBC.

    View details for DOI 10.1186/bcr2727

    View details for Web of Science ID 000285506100017

    View details for PubMedID 20939870

  • Effects of Conjugated Equine Estrogens on Cognition and Affect in Postmenopausal Women with Prior Hysterectomy JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Resnick, S. M., Espeland, M. A., An, Y., Maki, P. M., Coker, L. H., Jackson, R., Stefanick, M. L., Wallace, R., Rapp, S. R. 2009; 94 (11): 4152-4161

    Abstract

    Different menopausal hormone therapies may have varied effects on specific cognitive functions. We previously reported that conjugated equine estrogens (CEE) with medroxyprogesterone acetate had a negative impact on verbal memory but tended to impact figural memory positively over time in older postmenopausal women.The objective of the study was to determine the effects of unopposed CEE on changes in domain-specific cognitive function and affect in older postmenopausal women with prior hysterectomy.This was a randomized, double blind, placebo-controlled clinical trial.The study was conducted at 14 of 40 Women's Health Initiative (WHI) clinical centers.Participants were 886 postmenopausal women with prior hysterectomy, aged 65 yr and older (mean 74 yr), free of probable dementia, and enrolled in the WHI and WHI Memory Study (WHIMS) CEE-Alone trial for a mean of 3 yr and followed up for a mean of 2.70 yr.Intervention was 0.625 mg of CEE daily or placebo.Annual rates of change in specific cognitive functions and affect, adjusted for time since randomization, were measured.Compared with placebo, unopposed CEE was associated with lower spatial rotational ability (P < 0.01) at initial assessment (after 3 yr of treatment), a difference that diminished over 2.7 yr of continued treatment. CEE did not significantly influence change in other cognitive functions and affect.CEE did not improve cognitive functioning in postmenopausal women with prior hysterectomy. CEE was associated with lower spatial rotational performance after an average of 3 yr of treatment. Overall, CEE does not appear to have enduring effects on rates of domain-specific cognitive change in older postmenopausal women.

    View details for DOI 10.1210/jc.2009-1340

    View details for Web of Science ID 000271470800006

    View details for PubMedID 19850684

  • Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial LANCET Chlebowski, R. T., Schwartz, A. G., Wakelee, H., Anderson, G. L., Stefanick, M. L., Manson, J. E., Rodabough, R. J., Chien, J. W., Wactawski-Wende, J., Gass, M., Kotchen, J. M., Johnson, K. C., O'Sullivan, M. J., Ockene, J. K., Chen, C., Hubbell, F. A. 2009; 374 (9697): 1243-1251

    Abstract

    In the post-intervention period of the Women's Health Initiative (WHI) trial, women assigned to treatment with oestrogen plus progestin had a higher risk of cancer than did those assigned to placebo. Results also suggested that the combined hormone therapy might increase mortality from lung cancer. To assess whether such an association exists, we undertook a post-hoc analysis of lung cancers diagnosed in the trial over the entire follow-up period.The WHI study was a randomised, double-blind, placebo-controlled trial undertaken in 40 centres in the USA. 16 608 postmenopausal women aged 50-79 years with an intact uterus were randomly assigned by a computerised, stratified, permuted block algorithm to receive a once-daily tablet of 0.625 mg conjugated equine oestrogen plus 2.5 mg medroxyprogesterone acetate (n=8506) or matching placebo (n=8102). We assessed incidence and mortality rates for all lung cancer, small-cell lung cancer, and non-small-cell lung cancer by use of data from treatment and post-intervention follow-up periods. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00000611.After a mean of 5.6 years (SD 1.3) of treatment and 2.4 years (0.4) of additional follow-up, 109 women in the combined hormone therapy group had been diagnosed with lung cancer compared with 85 in the placebo group (incidence per year 0.16%vs 0.13%; hazard ratio [HR] 1.23, 95% CI 0.92-1.63, p=0.16). 96 women assigned to combined therapy had non-small-cell lung cancer compared with 72 assigned to placebo (0.14%vs 0.11%; HR 1.28, 0.94-1.73, p=0.12). More women died from lung cancer in the combined hormone therapy group than in the placebo group (73 vs 40 deaths; 0.11%vs 0.06%; HR 1.71, 1.16-2.52, p=0.01), mainly as a result of a higher number of deaths from non-small-cell lung cancer in the combined therapy group (62 vs 31 deaths; 0.09%vs 0.05%; HR 1.87, 1.22-2.88, p=0.004). Incidence and mortality rates of small-cell lung cancer were similar between groups.Although treatment with oestrogen plus progestin in postmenopausal women did not increase incidence of lung cancer, it increased the number of deaths from lung cancer, in particular deaths from non-small-cell lung cancer. These findings should be incorporated into risk-benefit discussions with women considering combined hormone therapy, especially those with a high risk of lung cancer.National Heart, Lung and Blood Institute, National Institutes of Health.

    View details for DOI 10.1016/S0140-6736(09)61526-9

    View details for Web of Science ID 000270852500030

    View details for PubMedID 19767090

  • Histories including number of falls may improve risk prediction for certain non-vertebral fractures in older men INJURY PREVENTION Faulkner, K. A., Chan, B. K., Cauley, J. A., Marshall, L. M., Ensrud, K. E., Stefanick, M. L., Orwoll, E. S. 2009; 15 (5): 307-311

    Abstract

    To determine whether information on number of falls on a falls history screen predicts risk of non-vertebral and hip fracture.A cohort of 5995 community-dwelling men aged 65 years and older (mean 73.7) was followed over 7.2 years for incident non-vertebral fractures. Cox proportional hazard models were used to calculate hazard ratios (HRs) (95% CI) for incident fracture comparing a history of one and two or more falls with no falls. Models were adjusted for age, clinic, body mass index, height, femoral neck bone mineral density and whether the participant had a non-trauma fracture after the age of 50. p

    View details for DOI 10.1136/ip.2009.021915

    View details for Web of Science ID 000270485400004

    View details for PubMedID 19805598

  • Sex Hormones and Frailty in Older Men: The Osteoporotic Fractures in Men (MrOS) Study JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Cawthon, P. M., Ensrud, K. E., Laughlin, G. A., Cauley, J. A., Dam, T. L., Barrett-Connor, E., Fink, H. A., Hoffman, A. R., Lau, E., Lane, N. E., Stefanick, M. L., Cummings, S. R., Orwoll, E. S. 2009; 94 (10): 3806-3815

    Abstract

    As men age, the prevalence of frailty increases whereas levels of androgens decline. Little is known about the relation between these factors.The aim of this study was to assess cross-sectional and longitudinal associations of estradiol, bioavailable estradiol, testosterone, bioavailable testosterone (bioT), and SHBG with frailty status.The Osteoporotic Fractures in Men (MrOS) study was conducted at six U.S. clinical centers.A total of 1469 community-dwelling men at least 65 yr old with baseline data participated; 1245 men had frailty status reassessed 4.1 yr later.Proportional odds models estimated the likelihood of greater frailty status. Frail men had at least three of the following: weakness, slowness, low activity, exhaustion, and shrinking/sarcopenia; intermediate men had one or two criteria; and robust men had none. At follow-up, death was included as an additional ordinal outcome. Sex hormones were assayed by spectrometry/chromatographic methods.In cross-sectional analyses, men in the lowest quartile of bioT had 1.39-fold (95% confidence interval, 1.02, 1.91) increased odds of greater frailty status compared to men in the highest quartile after adjustment for covariates including age, body size, health status, and medical conditions. In age-adjusted longitudinal analyses, men in the lowest quartile of bioT had 1.51-fold (95% confidence interval, 1.10, 2.07) increased odds of greater frailty status 4.1 yr later. This association was largely attenuated by adjustment for covariates. No other hormones were associated in a cross-sectional or longitudinal manner with frailty status after adjustment.Low levels of bioT were independently associated with worse baseline frailty status. Frailty status should be considered as an outcome in trials of testosterone supplementation.

    View details for DOI 10.1210/jc.2009-0417

    View details for Web of Science ID 000270526500025

    View details for PubMedID 19737923

  • Vasomotor Symptoms, Adoption of a Low-Fat Dietary Pattern, and Risk of Invasive Breast Cancer: A Secondary Analysis of the Women's Health Initiative Randomized Controlled Dietary Modification Trial JOURNAL OF CLINICAL ONCOLOGY Caan, B. J., Aragaki, A., Thomson, C. A., Stefanick, M. L., Chlebowski, R., Hubbell, F. A., Tinker, L., Vitolins, M., Rajkovic, A., Bueche, M., Ockene, J. 2009; 27 (27): 4500-4507

    Abstract

    To assess whether the effect of a low-fat dietary pattern on breast cancer incidence varied by report of baseline vasomotor symptoms.Postmenopausal women age 50 to 79 years enrolled onto the Women's Health Initiative (WHI) Dietary Modification trial from 1993 to 1998 were randomly assigned to a low-fat dietary intervention (n = 19,541) or comparison (n = 29,294). Presence of vasomotor symptoms at baseline was ascertained from a 34-item self-report symptom inventory. Women were queried semi-annually for a new diagnosis of breast cancer. Each case report was verified by medical record and pathology report review by centrally trained WHI physician adjudicators.Among participants who reported hot flashes (HFs) at baseline (n = 3,375), those assigned to the low-fat diet had a breast cancer rate of 0.27 compared with their counterparts in the control group who had a rate of 0.41 (hazard ratio [HR] = 0.65; 95% CI, 0.42 to 1.01). Among women reporting no HFs (n = 45,160), the breast cancer rate was 0.42 in those assigned to the low-fat diet compared with 0.46 in the control group (HR = 0.93; 95% CI, 0.84 to 1.03; P for interaction = .12 by HF status). Furthermore, the dietary benefits observed seemed to be specific to estrogen receptor (ER) -positive/progesterone receptor (PR) -positive tumors (ER positive/PR positive v other, P for risk = .03). Although women with and without HFs differed with regard to breast cancer risk factors, the effect of the diet intervention on breast cancer incidence by HF status was consistent across risk factor strata.The results of this trial, which are hypothesis generating, suggest that HFs may identify a subgroup of postmenopausal women whose risk of invasive breast cancer might be reduced with the adoption of a low-fat eating pattern.

    View details for DOI 10.1200/JCO.2008.20.0493

    View details for Web of Science ID 000270019900012

    View details for PubMedID 19687338

  • A Longitudinal Study of the Metabolic Syndrome and Risk of Postmenopausal Breast Cancer CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Kabat, G. C., Kim, M., Chlebowski, R. T., Khandekar, J., Ko, M. G., McTiernan, A., Neuhouser, M. L., Parker, D. R., Shikany, J. M., Stefanick, M. L., Thomson, C. A., Rohan, T. E. 2009; 18 (7): 2046-2053

    Abstract

    The metabolic syndrome, characterized by abdominal obesity, high blood glucose levels, impaired glucose tolerance, dyslipidemia, and hypertension, is associated with increased risk of type 2 diabetes and coronary heart disease. Several studies have examined the association of the individual components of the metabolic syndrome with breast cancer; to date, however, no study has assessed the metabolic syndrome per se in relation to breast cancer risk. Furthermore, previous studies have relied only on baseline assessment of components of the syndrome. Therefore, we assessed the association of the metabolic syndrome with the risk of postmenopausal breast cancer among women in the 6% sample of subjects in the Women's Health Initiative clinical trial and the 1% sample of women in the observational study who had repeated measurements of the components of the syndrome during follow-up. We used Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals for the association of breast cancer risk with the presence of the metabolic syndrome, as well as its components, at baseline and in time-dependent analyses. After exclusion of women with diabetes, among 4,888 women with baseline measurements, 165 incident cases of breast cancer were ascertained over a median of 8 years of follow-up. The presence of the metabolic syndrome at baseline was not associated with altered risk. Of the individual components measured at baseline, diastolic blood pressure showed a borderline positive association with breast cancer. In time-dependent covariate analyses, however, certain scenarios indicated a positive association between the metabolic syndrome and breast cancer, due primarily to positive associations with serum glucose, serum triglycerides, and diastolic blood pressure.

    View details for DOI 10.1158/1055-9965.EPI-09-0235

    View details for Web of Science ID 000268059700015

    View details for PubMedID 19567502

  • Dietary change and reduced breast cancer events among women without hot flashes after treatment of early-stage breast cancer: subgroup analysis of the Women's Healthy Eating and Living Study AMERICAN JOURNAL OF CLINICAL NUTRITION Pierce, J. P., Natarajan, L., Caan, B. J., Flatt, S. W., Kealey, S., Gold, E. B., Hajek, R. A., Newman, V. A., Rock, C. L., Pu, M., Saquib, N., Stefanick, M. L., Thomson, C. A., Parker, B. 2009; 89 (5): S1565-S1571
  • Colorectal Cancer in Relation to Postmenopausal Estrogen and Estrogen Plus Progestin in the Women's Health Initiative Clinical Trial and Observational Study CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Prentice, R. L., Pettinger, M., Beresford, S. A., Wactawski-Wende, J., Hubbell, F. A., Stefanick, M. L., Chlebowski, R. T. 2009; 18 (5): 1531-1537

    Abstract

    Colorectal cancer incidence was reduced among women assigned to active treatment in the Women's Health Initiative (WHI) estrogen plus progestin-randomized trial, but the interpretation was obscured by an associated later stage of diagnosis. In contrast, the estrogen-alone trial showed no incidence reduction or differential stage at diagnosis. Here, data from the WHI observational study are considered, in conjunction with colorectal cancer mortality data from the hormone therapy trials, in an attempt to clarify postmenopausal hormone therapy effects. Participants andPostmenopausal women ages 50 to 79 years at WHI enrollment. Estrogen-alone analyses include 21,552 and 10,739 women who were posthysterectomy from the observational study and clinical trial, respectively. Estrogen plus progestin analyses include 32,084 and 16,608 observational study and clinical trial women with uterus. Colorectal cancers were verified by central medical and pathology report review.Hazard ratios (95% confidence intervals) from the WHI observational study were 0.80 (0.53-1.20) for estrogen and 1.15 (0.74-1.79) for estrogen plus progestin, with, respectively, 168 and 175 women diagnosed with colorectal cancer. Delayed diagnosis with estrogen plus progestin is not evident in the observational study. No protective effect on colorectal cancer mortality in the estrogen plus progestin trial is seen over an 8-year intervention and follow-up period.Hazard ratio patterns in the WHI clinical trial and observational study do not provide strong evidence of a clinically important colorectal cancer benefit with either estrogen-alone or estrogen plus progestin over 7 to 8 years of treatment and follow-up.

    View details for DOI 10.1158/1055-9965.EPI-08-1209

    View details for Web of Science ID 000266081500027

    View details for PubMedID 19423530

  • Dietary change and reduced breast cancer events among women without hot flashes after treatment of early-stage breast cancer: subgroup analysis of the Women's Healthy Eating and Living Study. American journal of clinical nutrition Pierce, J. P., Natarajan, L., Caan, B. J., Flatt, S. W., Kealey, S., Gold, E. B., Hajek, R. A., Newman, V. A., Rock, C. L., Pu, M., Saquib, N., Stefanick, M. L., Thomson, C. A., Parker, B. 2009; 89 (5): 1565S-1571S

    Abstract

    A diet high in vegetables, fruit, and fiber and low in fat decreased additional risk of secondary breast cancer events in women without hot flashes (HF-) compared with that in women with hot flashes (HF+), possibly through lowered concentrations of circulating estrogens.The objective was to investigate the intervention effect by baseline quartiles of dietary pattern among breast cancer survivors in the HF- subgroup of the Women's Healthy Eating and Living Study. Design: A randomized controlled trial compared a putative cancer prevention diet with a diet of 5 servings of vegetables and fruit daily in early-stage breast cancer survivors. Participants did not experience hot flashes at baseline (n = 896). We confirmed cancer status for 96% of participants approximately 7.3 y after enrollment.The study intervention achieved a large between-group difference in dietary pattern that, at 4 y, was not significantly different across baseline quartiles of dietary pattern. The intervention group experienced fewer breast cancer events than did the comparison group for all of the baseline quartiles. This difference was significant only in upper baseline quartiles of intake of vegetables, fruit, and fiber and in the lowest quartile of fat. A significant trend for fewer breast cancer events was observed across quartiles of vegetable-fruit and fiber consumption.The secondary analysis showing the decreased risk in the HF- subgroup was not explained by amount of change in dietary pattern achieved. The difference was strongest in the quartile with the most putatively cancer-preventive dietary pattern at baseline.

    View details for DOI 10.3945/ajcn.2009.26736F

    View details for PubMedID 19339393

  • Calcium Plus Vitamin D Supplementation and Mortality in Postmenopausal Women: The Women's Health Initiative Calcium-Vitamin D Randomized Controlled Trial JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LaCroix, A. Z., Kotchen, J., Anderson, G., Brzyski, R., Cauley, J. A., Cummings, S. R., Gass, M., Johnson, K. C., Ko, M., Larson, J., Manson, J. E., Stefanick, M. L., Wactawski-Wende, J. 2009; 64 (5): 559-567

    Abstract

    Calcium and vitamin D (CaD) supplementation trials including the Women's Health Initiative (WHI) trial of CaD have shown nonsignificant reductions in total mortality. This report examines intervention effects on total and cause-specific mortality by age and adherence.The WHI CaD trial was a randomized, double-blind, placebo-controlled trial that enrolled 36,282 postmenopausal women aged 51-82 years from 40 U.S. clinical centers. Women were assigned to 1,000 mg of elemental calcium carbonate and 400 IU of vitamin D(3) daily or placebo with average follow-up of 7.0 years.The hazard ratio (HR) for total mortality was 0.91 (95% confidence interval [CI], 0.83-1.01) with 744 deaths in women randomized to CaD versus 807 deaths in the placebo group. HRs were in the direction of reduced risk but nonsignificant for stroke and cancer mortality, but near unity for coronary heart disease and other causes of death. HRs for total mortality were 0.89 in the 29,942 women younger than 70 years (95% CI, 0.79-1.01) and 0.95 in the 6,340 women aged 70 and older (95% CI, 0.80-1.12; p value for age interaction = .10). No statistically significant interactions were observed for any baseline characteristics. Treatment effects did not vary significantly by season.In the WHI CaD trial, supplementation did not have a statistically significant effect on mortality rates but the findings support the possibility that these supplements may reduce mortality rates in postmenopausal women. These data can neither support nor refute recommendations for higher dose vitamin D supplementation to reduce cancer or total mortality.

    View details for DOI 10.1093/gerona/glp006

    View details for Web of Science ID 000265095900007

    View details for PubMedID 19221190

  • Biomarker-calibrated Energy and Protein Consumption and Increased Cancer Risk Among Postmenopausal Women AMERICAN JOURNAL OF EPIDEMIOLOGY Prentice, R. L., Shaw, P. A., Bingham, S. A., Beresford, S. A., Caan, B., Neuhouser, M. L., Patterson, R. E., Stefanick, M. L., Satterfield, S., Thomson, C. A., Snetselaar, L., Thomas, A., Tinker, L. F. 2009; 169 (8): 977-989

    Abstract

    The authors previously reported equations, derived from the Nutrient Biomarker Study within the Women's Health Initiative, that produce calibrated estimates of energy, protein, and percentage of energy from protein consumption from corresponding food frequency questionnaire estimates and data on other factors, such as body mass index, age, and ethnicity. Here, these equations were applied to yield calibrated consumption estimates for 21,711 women enrolled in the Women's Health Initiative dietary modification trial comparison group and 59,105 women enrolled in the observational study. These estimates were related prospectively to total and site-specific invasive cancer incidence (1993-2005). In combined cohort analyses that do not control for body mass, uncalibrated energy was not associated with total cancer incidence or site-specific cancer incidence for most sites, whereas biomarker-calibrated energy was positively associated with total cancer (hazard ratio = 1.18, 95% confidence interval: 1.10, 1.27, for 20% consumption increase), as well as with breast, colon, endometrial, and kidney cancer (respective hazard ratios of 1.24, 1.35, 1.83, and 1.47). Calibrated protein was weakly associated, and calibrated percentage of energy from protein was inversely associated, with total cancer. Calibrated energy and body mass index associations were highly interdependent. Implications for the interpretation of nutritional epidemiology studies are described.

    View details for DOI 10.1093/aje/kwp008

    View details for Web of Science ID 000264634900008

    View details for PubMedID 19258487

  • Association Between Sleep Architecture and Measures of Body Composition SLEEP Rao, M. N., Blackwell, T., Susan, R., Stefanick, M. L., Ancoli-Israel, S., Stone, K. L. 2009; 32 (4): 483-490

    Abstract

    To determine whether slow wave sleep (SWS) is inversely associated with body mass index (BMI) and other measures of body composition.Cross-sectional, observational study.Community-based.2745 older men from the MrOS Sleep Study who completed polysomnography. Interventions: N/A.SWS as a percentage of total sleep duration was obtained from in-home, overnight polysomnography. Measures of body composition including BMI, weight, waist circumference and total body fat mass were determined by standard techniques. Other covariates in the analysis were age, race/ethnicity, clinic site, physical activity, respiratory disturbance index (RDI), total sleep time, and sleep efficiency. In the multivariate analysis, there was a significant inverse association between quartiles of SWS and BMI (P-trend = 0.0095). Older men in the lowest quartile of SWS had an average BMI of 27.4 kg/m2, compared to 26.8 for those in the highest quartile of SWS. This association was attenuated in men with RDI > or = 15. Furthermore, participants in the lowest quartile of SWS had a 1.4-fold increased odds for obesity (P = 0.03, 95% CI 1.0, 1.8) compared to those in the highest quartile. A similar inverse association between SWS and waist circumference as well as weight was observed. REM sleep was not associated with measures of body composition.Independent of sleep duration, percentage time in SWS is inversely associated with BMI and other measures of body composition in this population of older men. Participants in the lowest quartile of SWS (compared to those in the highest quartile) are at increased risk for obesity.

    View details for Web of Science ID 000264543300006

    View details for PubMedID 19413142

  • Breast Cancer after Use of Estrogen plus Progestin in Postmenopausal Women NEW ENGLAND JOURNAL OF MEDICINE Chlebowski, R. T., Kuller, L. H., Prentice, R. L., Stefanick, M. L., Manson, J. E., Gass, M., Aragaki, A. K., Ockene, J. K., Lane, D. S., Sarto, G. E., Rajkovic, A., Schenken, R., Hendrix, S. L., Ravdin, P. M., Rohan, T. E., Yasmeen, S., Anderson, G. 2009; 360 (6): 573-587

    Abstract

    Following the release of the 2002 report of the Women's Health Initiative (WHI) trial of estrogen plus progestin, the use of menopausal hormone therapy in the United States decreased substantially. Subsequently, the incidence of breast cancer also dropped, suggesting a cause-and-effect relation between hormone treatment and breast cancer. However, the cause of this decrease remains controversial.We analyzed the results of the WHI randomized clinical trial--in which one study group received 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily and another group received placebo--and examined temporal trends in breast-cancer diagnoses in the WHI observational-study cohort. Risk factors for breast cancer, frequency of mammography, and time-specific incidence of breast cancer were assessed in relation to combined hormone use.In the clinical trial, there were fewer breast-cancer diagnoses in the group receiving estrogen plus progestin than in the placebo group in the initial 2 years of the study, but the number of diagnoses increased over the course of the 5.6-year intervention period. The elevated risk decreased rapidly after both groups stopped taking the study pills, despite a similar frequency of mammography. In the observational study, the incidence of breast cancer was initially about two times as high in the group receiving menopausal hormones as in the placebo group, but this difference in incidence decreased rapidly in about 2 years, coinciding with year-to-year reductions in combined hormone use. During this period, differences in the frequency of mammography between the two groups were unchanged.The increased risk of breast cancer associated with the use of estrogen plus progestin declined markedly soon after discontinuation of combined hormone therapy and was unrelated to changes in frequency of mammography.

    View details for Web of Science ID 000263028800004

    View details for PubMedID 19196674

  • Longitudinal Biological Exposure to Carotenoids Is Associated with Breast Cancer-Free Survival in the Women's Healthy Eating and Living Study CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Rock, C. L., Natarajan, L., Pu, M., Thomson, C. A., Flatt, S. W., Caan, B. J., Gold, E. B., Al-Delaimy, W. K., Newman, V. A., Hajek, R. A., Stefanick, M. L., Pierce, J. P. 2009; 18 (2): 486-494

    Abstract

    In some cohort studies, a high-vegetable diet has been associated with greater likelihood of recurrence-free survival in women diagnosed with breast cancer. Carotenoids are obtained primarily from vegetables and fruit and they exhibit biological activities that may specifically reduce the progression of mammary carcinogenesis. The present analysis examines the relationship between plasma carotenoids at enrollment and 1, 2 or 3, 4, and 6 years and breast cancer-free survival in the Women's Healthy Eating and Living Study participants (N = 3,043), who had been diagnosed with early-stage breast cancer. The primary end point was time to a second breast cancer event (a recurrence or new primary breast cancer). An average carotenoid concentration over time was estimated for each participant as the average area under the plasma carotenoid curve formed by the plasma carotenoid concentrations at scheduled clinic visits. Multiple regression Cox proportional hazards analysis with adjustment for prognostic and other factors was used to examine the association between carotenoids and breast cancer-free survival. A total of 508 (16.7%) breast cancer events occurred over a median 7.12 years follow-up. Compared with the lowest tertile, the hazard ratio for the medium/high plasma carotenoid tertiles was 0.67 (95% confidence interval, 0.54-0.83) after adjustment. The interaction between the study group and tertile of average carotenoid concentration over time was not significant (P = 0.23). Higher biological exposure to carotenoids, when assessed over the time frame of the study, was associated with greater likelihood of breast cancer-free survival regardless of study group assignment.

    View details for DOI 10.1158/1055-9965.EPI-08-0809

    View details for Web of Science ID 000263547800016

    View details for PubMedID 19190138

  • Dietary Pattern Influences Breast Cancer Prognosis in Women Without Hot Flashes: The Women's Healthy Eating and Living Trial JOURNAL OF CLINICAL ONCOLOGY Gold, E. B., Pierce, J. P., Natarajan, L., Stefanick, M. L., Laughlin, G. A., Caan, B. J., Flatt, S. W., Emond, J. A., Saquib, N., Madlensky, L., Kealey, S., Wasserman, L., Thomson, C. A., Rock, C. L., Parker, B. A., Karanja, N., Jones, V., Hajek, R. A., Pu, M., Mortimer, J. E. 2009; 27 (3): 352-359

    Abstract

    To determine whether a low-fat diet high in vegetables, fruit, and fiber differentially affects prognosis in breast cancer survivors with hot flashes (HF) or without HF after treatment.A secondary analysis was conducted on 2,967 breast cancer survivors, age 18 to 70 years, who were randomly assigned between 1995 and 2000 in a multicenter, controlled trial of a dietary intervention to prevent additional breast cancer events and observed through June 1, 2006. We compared the dietary intervention group with a group who received five-a-day dietary guidelines.Independent of HF status, a substantial between-group difference among those who did and did not receive dietary guidelines was achieved and maintained at 4 years in intake of vegetable/fruit servings per day (54% higher; 10 v 6.5 servings/d, respectively), fiber (31% higher; 25.5 v 19.4 g/d, respectively), and percent energy from fat (14% lower; 26.9% v 31.3%, respectively). Adjusting for tumor characteristics and antiestrogen treatment, HF-negative women assigned to the intervention had 31% fewer events than HF-negative women assigned to the comparison group (hazard ratio [HR] = 0.69; 95% CI, 0.51 to 0.93; P = .02). The intervention did not affect prognosis in the women with baseline HFs. Furthermore, compared with HF-negative women assigned to the comparison group, HF-positive women had significantly fewer events in both the intervention (HR = 0.77; 95% CI, 0.59 to 1.00; P = .05) and comparison groups (HR = 0.65; 95% CI, 0.49 to 0.85; P = .002).A diet with higher vegetable, fruit, and fiber and lower fat intakes than the five-a-day diet may reduce risk of additional events in HF-negative breast cancer survivors. This suggestive finding needs confirmation in a trial in which it is the primary hypothesis.

    View details for DOI 10.1200/JCO.2008.16.1067

    View details for Web of Science ID 000262499100007

    View details for PubMedID 19075284

  • Postmenopausal hormone therapy and subclinical cerebrovascular disease The WHIMS-MRI Study NEUROLOGY Coker, L. H., Hogan, P. E., Bryan, N. R., Kuller, L. H., Margolis, K. L., Bettermann, K., Wallace, R. B., Lao, Z., Freeman, R., Stefanick, M. L., Shumaker, S. A. 2009; 72 (2): 125-134

    Abstract

    The Women's Health Initiative Memory Study (WHIMS) hormone therapy (HT) trials reported that conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA) increases risk for all-cause dementia and global cognitive decline. WHIMS MRI measured subclinical cerebrovascular disease as a possible mechanism to explain cognitive decline reported in WHIMS.We contacted 2,345 women at 14 WHIMS sites; scans were completed on 1,424 (61%) and 1,403 were accepted for analysis. The primary outcome measure was total ischemic lesion volume on brain MRI. Mean duration of on-trial HT or placebo was 4 (CEE+MPA) or 5.6 years (CEE-Alone) and scans were conducted an average of 3 (CEE+MPA) or 1.4 years (CEE-Alone) post-trial termination. Cross-sectional analysis of MRI lesions was conducted; general linear models were fitted to assess treatment group differences using analysis of covariance. A (two-tailed) critical value of alpha = 0.05 was used.In women evenly matched within trials at baseline, increased lesion volumes were significantly related to age, smoking, history of cardiovascular disease, hypertension, lower post-trial global cognition scores, and increased incident cases of on- or post-trial mild cognitive impairment or probable dementia. Mean ischemic lesion volumes were slightly larger for the CEE+MPA group vs placebo, except for the basal ganglia, but the differences were not significant. Women assigned to CEE-Alone had similar mean ischemic lesion volumes compared to placebo.Conjugated equine estrogen-based hormone therapy was not associated with a significant increase in ischemic brain lesion volume relative to placebo. This finding was consistent within each trial and in pooled analyses across trials.

    View details for DOI 10.1212/01.wnl.0000339036.88842.9e

    View details for Web of Science ID 000262393200005

    View details for PubMedID 19139363

  • Postmenopausal hormone therapy and regional brain volumes The WHIMS-MRI Study NEUROLOGY Resnick, S. M., Espeland, M. A., Jaramillo, S. A., Hirsch, C., Stefanick, M. L., Murray, A. M., Ockene, J., Davatzikos, C. 2009; 72 (2): 135-142

    Abstract

    To determine whether menopausal hormone therapy (HT) affects regional brain volumes, including hippocampal and frontal regions.Brain MRI scans were obtained in a subset of 1,403 women aged 71-89 years who participated in the Women's Health Initiative Memory Study (WHIMS). WHIMS was an ancillary study to the Women's Health Initiative, which consisted of two randomized, placebo-controlled trials: 0.625 mg conjugated equine estrogens (CEE) with or without 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet. Scans were performed, on average, 3.0 years post-trial for the CEE + MPA trial and 1.4 years post-trial for the CEE-Alone trial; average on-trial follow-up intervals were 4.0 years for CEE + MPA and 5.6 years for CEE-Alone. Total brain, ventricular, hippocampal, and frontal lobe volumes, adjusted for age, clinic site, estimated intracranial volume, and dementia risk factors, were the main outcome variables.Compared with placebo, covariate-adjusted mean frontal lobe volume was 2.37 cm(3) lower among women assigned to HT (p = 0.004), mean hippocampal volume was slightly (0.10 cm(3)) lower (p = 0.05), and differences in total brain volume approached significance (p = 0.07). Results were similar for CEE + MPA and CEE-Alone. HT-associated reductions in hippocampal volumes were greatest in women with the lowest baseline Modified Mini-Mental State Examination scores (scores <90).Conjugated equine estrogens with or without MPA are associated with greater brain atrophy among women aged 65 years and older; however, the adverse effects are most evident in women experiencing cognitive deficits before initiating hormone therapy.

    View details for DOI 10.1212/01.wnl.0000339037.76336.cf

    View details for Web of Science ID 000262393200006

    View details for PubMedID 19139364

  • The association between sleep duration and obesity in older adults INTERNATIONAL JOURNAL OF OBESITY Patel, S. R., Blackwell, T., Redline, S., Ancoli-Israel, S., Cauley, J. A., Hillier, T. A., Lewis, C. E., Orwoll, E. S., Stefanick, M. L., Taylor, B. C., Yaffe, K., Stone, K. L. 2008; 32 (12): 1825-1834

    Abstract

    Reduced sleep has been reported to predict obesity in children and young adults. However, studies based on self-report have been unable to identify an association in older populations. In this study, the cross-sectional associations between sleep duration measured objectively and measures of weight and body composition were assessed in two cohorts of older adults.Wrist actigraphy was performed for a mean (s.d.) of 5.2 (0.9) nights in 3055 men (age: 67-96 years) participating in the Osteoporotic Fractures in Men Study (MrOS) and 4.1 (0.8) nights in 3052 women (age: 70-99 years) participating in the Study of Osteoporotic Fractures (SOF). A subgroup of 2862 men and 455 women also underwent polysomnography to measure sleep apnea severity.Compared to those sleeping an average of 7-8 h per night, and after adjusting for multiple risk factors and medical conditions, a sleep duration of less than 5 h was associated with a body mass index (BMI) that was on average 2.5 kg/m(2) (95% confidence interval (CI): 2.0-2.9) greater in men and 1.8 kg/m(2) (95% CI: 1.1-2.4) greater in women. The odds of obesity (BMI >or= 30 kg/m(2)) was 3.7-fold greater (95% CI: 2.7-5.0) in men and 2.3-fold greater in women (95% CI: 1.6-3.1) who slept less than 5 h. Short sleep was also associated with central body fat distribution and increased percent body fat. These associations persisted after adjusting for sleep apnea, insomnia and daytime sleepiness.In older men and women, actigraphy-ascertained reduced sleep durations are strongly associated with greater adiposity.

    View details for DOI 10.1038/ijo.2008.198

    View details for Web of Science ID 000261695400009

    View details for PubMedID 18936766

  • Sleep Duration and Risk of Ischemic Stroke in Postmenopausal Women STROKE Chen, J., Brunner, R. L., Ren, H., Wassertheil-Smoller, S., Larson, J. C., Levine, D. W., Allison, M., Naughton, M. J., Stefanick, M. L. 2008; 39 (12): 3185-3192

    Abstract

    Many studies have shown a U-shape association between sleep duration and mortality, but epidemiological evidence linking cardiovascular diseases with habitual sleep patterns is limited and mixed.We conducted a prospective study on 93 175 older women (aged 50 to 79 years) in the Women's Health Initiative Observational study cohort to examine the risk of ischemic stroke in relation to self-reported sleep duration. Cox models were used to investigate the putative associations, adjusting for multiple sociodemographic and lifestyle factors, depression, snoring, sleepiness symptoms, and other cardiovascular disease-related clinical characteristics.At baseline, 8.3% of subjects had reported their sleep duration as or=9 hours/night). After an average of 7.5 years of follow-up, 1166 cases of ischemic stroke had occurred. Multivariable-adjusted relative risk (RR) and 95% CI for ischemic stroke (using a sleep time of 7 hours/night as the reference) were 1.14 (0.97, 1.33), 1.24 (1.04, 1.47), and 1.70 (1.32, 2.21) for women reporting or=9 hours of sleep. A modestly stronger association with sleep duration or=9 hours/night) need further elucidation.

    View details for DOI 10.1161/STROKEAHA.108.521773

    View details for Web of Science ID 000261224800010

    View details for PubMedID 18635832

  • Calcium Plus Vitamin D Supplementation and the Risk of Breast Cancer JOURNAL OF THE NATIONAL CANCER INSTITUTE Chlebowski, R. T., Johnson, K. C., Kooperberg, C., Pettinger, M., Wactawski-Wende, J., Rohan, T., Rossouw, J., Lane, D., O'Sullivan, M. J., Yasmeen, S., Hiatt, R. A., Shikany, J. M., Vitolins, M., Khandekar, J., Hubbell, F. A. 2008; 100 (22): 1581-1591

    Abstract

    Although some observational studies have associated higher calcium intake and especially higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk, no randomized trial has evaluated these relationships.Postmenopausal women (N = 36 282) who were enrolled in a Women's Health Initiative clinical trial were randomly assigned to 1000 mg of elemental calcium with 400 IU of vitamin D(3) daily or placebo for a mean of 7.0 years to determine the effects of supplement use on incidence of hip fracture. Mammograms and breast exams were serially conducted. Invasive breast cancer was a secondary outcome. Baseline serum 25-hydroxyvitamin D levels were assessed in a nested case-control study of 1067 case patients and 1067 control subjects. A Cox proportional hazards model was used to estimate the risk of breast cancer associated with random assignment to calcium with vitamin D(3). Associations between 25-hydroxyvitamin D serum levels and total vitamin D intake, body mass index (BMI), recreational physical activity, and breast cancer risks were evaluated using logistic regression models. Statistical tests were two-sided.Invasive breast cancer incidence was similar in the two groups (528 supplement vs 546 placebo; hazard ratio = 0.96; 95% confidence interval = 0.85 to 1.09). In the nested case-control study, no effect of supplement group assignment on breast cancer risk was seen. Baseline 25-hydroxyvitamin D levels were modestly correlated with total vitamin D intake (diet and supplements) (r = 0.19, P < .001) and were higher among women with lower BMI and higher recreational physical activity (both P < .001). Baseline 25-hydroxyvitamin D levels were not associated with breast cancer risk in analyses that were adjusted for BMI and physical activity (P(trend) = .20).Calcium and vitamin D supplementation did not reduce invasive breast cancer incidence in postmenopausal women. In addition, 25-hydroxyvitamin D levels were not associated with subsequent breast cancer risk. These findings do not support a relationship between total vitamin D intake and 25-hydroxyvitamin D levels with breast cancer risk.

    View details for DOI 10.1093/jnci/djn360

    View details for Web of Science ID 000261170000007

    View details for PubMedID 19001601

  • Conjugated equine estrogens and colorectal cancer incidence and survival: The women's health initiative randomized clinical trial CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Ritenbaugh, C., Stanford, J. L., Wu, L., Shikany, J. M., Schoen, R. E., Stefanick, M. L., Taylor, V., Garland, C., Frank, G., Lane, D., Mason, E., Mcneeley, S. G., Ascensao, J., Chlebowski, R. T. 2008; 17 (10): 2609-2618

    Abstract

    In separate Women's Health Initiative randomized trials, combined hormone therapy with estrogen plus progestin reduced colorectal cancer incidence but estrogen alone in women with hysterectomy did not. We now analyze features of the colorectal cancers that developed and examine the survival of women following colorectal cancer diagnosis in the latter trial.10,739 postmenopausal women who were 50 to 79 years of age and had undergone hysterectomy were randomized to conjugated equine estrogens (0.625 mg/d) or matching placebo. Colorectal cancer incidence was a component of the monitoring global index of the study but was not a primary study endpoint. Colorectal cancers were verified by central medical record and pathology report review. Bowel exam frequency was not protocol defined, but information on their use was collected.After a median 7.1 years, there were 58 invasive colorectal cancers in the hormone group and 53 in the placebo group [hazard ratio, 1.12; 95% confidence interval (95% CI), 0.77-1.63]. Tumor size, stage, and grade were comparable in the two randomization groups. Bowel exam frequency was also comparable in the two groups. The cumulative mortality following colorectal cancer diagnosis among women in the conjugated equine estrogen group was 34% compared with 30% in the placebo group (hazard ratio, 1.34; 95% CI, 0.58-3.19).In contrast to the preponderance of observational studies, conjugated equine estrogens in a randomized clinical trial did not reduce colorectal cancer incidence nor improve survival after diagnosis.

    View details for DOI 10.1158/1055-9965.EPI-08-0385

    View details for Web of Science ID 000260051000013

    View details for PubMedID 18829444

  • Hip bone density predicts breast cancer risk independently of gail score - Results from the women's health initiative CANCER Chen, Z., Arendell, L., Aickin, M., Cauley, J., Lewis, C. E., Chlebowski, R., Nabel, E., Rossouw, J., Ludlam, S., Pottern, L., McGowan, J., Ford, L., Geller, N., Prentice, R., Anderson, G., LaCroix, A., Kooperberg, C. L., Patterson, R. E., McTiernan, A., Shumaker, S., Stein, E., Cummings, S., Wassertheil-Smoller, S., Hays, J., Manson, J., Assaf, A. R., Phillips, L., Beresford, S., Hsia, J., Chlebowski, R., Whitlock, E., Caan, B., Howard, B. V., Van Horn, L., Black, H., Stefanick, M. L., Lane, D., Jackson, R., Lewis, C. E., Bassford, T., Wactawski-Wende, J., Robbins, J., Hubbell, F. A., Judd, H., Langer, R. D., Gass, M., Limacher, M., Curb, D., Wallace, R., Ockene, J., Lasser, N., O'Sullivan, M. J., Margolis, K., Brunner, R., Heiss, G., Kuller, L., Johnson, K. C., Brzyski, R., Santo, G. E., Bonds, D., Henddx, S., Kotchen, J. M. 2008; 113 (5): 907-915

    Abstract

    The Gail model has been commonly used to estimate a woman's risk of breast cancer within a certain time period. High bone mineral density (BMD) is also a significant risk factor for breast cancer, but it appears to play no role in the Gail model. The objective of the current study was to investigate whether hip BMD predicts postmenopausal breast cancer risk independently of the Gail score.In this prospective study, 9941 postmenopausal women who had a baseline hip BMD and Gail score from the Women's Health Initiative were included in the analysis. Their average age was 63.0 +/- 7.4 years at baseline.After an average of 8.43 years of follow-up, 327 incident breast cancer cases were reported and adjudicated. In a multivariate Cox proportional hazards model, the hazards ratios (95% confidence interval [95% CI]) for incident breast cancer were 1.35 (95% CI, 1.05-1.73) for high Gail score (>or=1.67%) and 1.25 (95% CI, 1.11-1.40) for each unit of increase in the total hip BMD T-score. Restricting the analysis to women with both BMD and a Gail score above the median, a sharp increase in incident breast cancer for women with the highest BMD and Gail scores was found (P < .05).The contribution of BMD to the prediction of incident postmenopausal breast cancer across the entire population was found to be independent of the Gail score. However, among women with both high BMD and a high Gail score, there appears to be an interaction between these 2 factors. These findings suggest that BMD and Gail score may be used together to better quantify the risk of breast cancer.

    View details for DOI 10.1002/cncr.23674

    View details for Web of Science ID 000259069000007

    View details for PubMedID 18666209

  • Conjugated equine estrogens and breast cancer risk in the women's health initiative clinical trial and observational study AMERICAN JOURNAL OF EPIDEMIOLOGY Prentice, R. L., Chlebowski, R. T., Stefanick, M. L., Manson, J. E., Langer, R. D., Pettinger, M., Hendrix, S. L., Hubbell, F. A., Kooperberg, C., Kuller, L. H., Lane, D. S., McTiernan, A., O'Sullivan, M. J., Rossouw, J. E., Anderson, G. L. 2008; 167 (12): 1407-1415

    Abstract

    The Women's Health Initiative randomized controlled trial found a trend (p = 0.09) toward a lower breast cancer risk among women assigned to daily 0.625-mg conjugated equine estrogens (CEEs) compared with placebo, in contrast to an observational literature that mostly reports a moderate increase in risk with estrogen-alone preparations. In 1993-2004 at 40 US clinical centers, breast cancer hazard ratio estimates for this CEE regimen were compared between the Women's Health Initiative clinical trial and observational study toward understanding this apparent discrepancy and refining hazard ratio estimates. After control for prior use of postmenopausal hormone therapy and for confounding factors, CEE hazard ratio estimates were higher from the observational study compared with the clinical trial by 43% (p = 0.12). However, after additional control for time from menopause to first use of postmenopausal hormone therapy, the hazard ratios agreed closely between the two cohorts (p = 0.82). For women who begin use soon after menopause, combined analyses of clinical trial and observational study data do not provide clear evidence of either an overall reduction or an increase in breast cancer risk with CEEs, although hazard ratios appeared to be relatively higher among women having certain breast cancer risk factors or a low body mass index.

    View details for DOI 10.1093/aje/kwn090

    View details for Web of Science ID 000256755900002

    View details for PubMedID 18448442

  • Usefulness of baseline lipids and C-reactive protein in women receiving menopausal hormone therapy as predictors of treatment-related coronary events AMERICAN JOURNAL OF CARDIOLOGY Bray, P. F., Larson, J. C., LaCroix, A. Z., Manson, J., Limacher, M. C., Rossouw, J. E., Lasser, N. L., Lawson, W. E., Stefanick, M. L., Langer, R. D., Margolis, K. L. 2008; 101 (11): 1599-1605

    Abstract

    Blood lipids and high-sensitivity C-reactive protein (hs-CRP) are altered by hormone therapy. The goal of the present study was to determine whether lipids and hs-CRP have predictive value for hormone therapy benefit or risk for coronary heart disease events in postmenopausal women without previous cardiovascular disease. A nested case-control study was performed in the Women's Health Initiative hormone trials. Baseline lipids and hs-CRP were obtained from 271 incident patients with coronary heart disease (cases) and 707 controls. In a combined trial analysis, favorable lipid status at baseline tended to predict better coronary heart disease outcomes when using conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA). Women with a low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratio <2.5 had no increase in risk of coronary heart disease when using CEE with or without MPA (odds ratio 0.60, 95% confidence interval 0.34 to 1.06), whereas women with an LDL/HDL cholesterol ratio > or =2.5 had increased risk of coronary heart disease (odds ratio 1.73, 95% confidence interval 1.18 to 2.53, p for interaction = 0.02). Low hs-CRP added marginally to the value of LDL/HDL ratio <2.5 when predicting coronary heart disease benefit on hormone therapy. In conclusion, postmenopausal women with undesirable lipid levels had excess coronary heart disease risk when using CEE with or without MPA. However, women with favorable lipid levels, especially LDL/HDL cholesterol ratio <2.5, did not have increased risk of coronary heart disease with CEE with or without MPA irrespective of hs-CRP.

    View details for DOI 10.1016/j.amjcard.2008.01.043

    View details for Web of Science ID 000256450700011

    View details for PubMedID 18489937

  • Use of recovery biomarkers to calibrate nutrient consumption self-reports in the Women's Health Initiative AMERICAN JOURNAL OF EPIDEMIOLOGY Neuhouser, M. L., Tinker, L., Shaw, P. A., Schoeller, D., Bingham, S. A., Van Horn, L., Beresford, S. A., Caan, B., Thomson, C., Satterfield, S., Kuller, L., Heiss, G., Smit, E., Sarto, G., Ockene, J., Stefanick, M. L., Assaf, A., Runswick, S., Prentice, R. L. 2008; 167 (10): 1247-1259

    Abstract

    Underreporting of energy consumption by self-report is well-recognized, but previous studies using recovery biomarkers have not been sufficiently large to establish whether participant characteristics predict misreporting. In 2004-2005, 544 participants in the Women's Health Initiative Dietary Modification Trial completed a doubly labeled water protocol (energy biomarker), 24-hour urine collection (protein biomarker), and self-reports of diet (assessed by food frequency questionnaire (FFQ)), exercise, and lifestyle habits; 111 women repeated all procedures after 6 months. Using linear regression, the authors estimated associations of participant characteristics with misreporting, defined as the extent to which the log ratio (self-reported FFQ/nutritional biomarker) was less than zero. Intervention women in the trial underreported energy intake by 32% (vs. 27% in the comparison arm) and protein intake by 15% (vs. 10%). Younger women had more underreporting of energy (p = 0.02) and protein (p = 0.001), while increasing body mass index predicted increased underreporting of energy and overreporting of percentage of energy derived from protein (p = 0.001 and p = 0.004, respectively). Blacks and Hispanics underreported more than did Caucasians. Correlations of initial measures with repeat measures (n = 111) were 0.72, 0.70, 0.46, and 0.64 for biomarker energy, FFQ energy, biomarker protein, and FFQ protein, respectively. Recovery biomarker data were used in regression equations to calibrate self-reports; the potential application of these equations to disease risk modeling is presented. The authors confirm the existence of systematic bias in dietary self-reports and provide methods of correcting for measurement error.

    View details for DOI 10.1093/aje/kwn026

    View details for Web of Science ID 000255756100013

    View details for PubMedID 18344516

  • Estrogen plus progestin therapy and breast cancer in recently postmenopausal women AMERICAN JOURNAL OF EPIDEMIOLOGY Prentice, R. L., Chlebowski, R. T., Stefanick, M. L., Manson, J. E., Pettinger, M., Hendrix, S. L., Hubbell, F. A., Kooperberg, C., Kuller, L. H., Lane, D. S., McTiernan, A., O'Sullivan, M. J., Rossouw, J. E., Anderson, G. L. 2008; 167 (10): 1207-1216

    Abstract

    The Women's Health Initiative trial found a modestly increased risk of invasive breast cancer with daily 0.625-mg conjugated equine estrogens plus 2.5-mg medroxyprogesterone acetate, with most evidence among women who had previously received postmenopausal hormone therapy. In comparison, observational studies mostly report a larger risk increase. To explain these patterns, the authors examined the effects of this regimen in relation to both prior hormone therapy and time from menopause to first use of postmenopausal hormone therapy ("gap time") in the Women's Health Initiative trial and in a corresponding subset of the Women's Health Initiative observational study. Postmenopausal women with a uterus enrolled at 40 US clinical centers during 1993-1998. The authors found that hazard ratios agreed between the two cohorts at a specified gap time and time from hormone therapy initiation. Combined trial and observational study data support an adverse effect on breast cancer risk. Women who initiate use soon after menopause, and continue for many years, appear to be at particularly high risk. For example, for a woman who starts soon after menopause and adheres to this regimen, estimated hazard ratios are 1.64 (95% confidence interval: 1.00, 2.68) over a 5-year period of use and 2.19 (95% confidence interval: 1.56, 3.08) over a 10-year period of use.

    View details for DOI 10.1093/aje/kwn044

    View details for Web of Science ID 000255756100009

    View details for PubMedID 18372396

  • Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Heiss, G., Wallace, R., Anderson, G. L., Aragaki, A., Beresford, S. A., Brzyski, R., Chlebowski, R. T., Gass, M., LaCroix, A., Manson, J. E., Prentice, R. L., Rossouw, J., Stefanick, M. L. 2008; 299 (9): 1036-1045

    Abstract

    The Women's Health Initiative (WHI) trial of estrogen plus progestin vs placebo was stopped early, after a mean 5.6 years of follow-up, because the overall health risks of hormone therapy exceeded its benefits.To report health outcomes at 3 years (mean 2.4 years of follow-up) after the intervention was stopped.The intervention phase was a double-blind, placebo-controlled, randomized trial of conjugated equine estrogens (CEE) 0.625 mg daily plus medroxyprogesterone acetate (MPA) 2.5 mg daily, in 16,608 women aged 50 through 79 years, recruited by 40 centers from 1993 to 1998. The postintervention phase commenced July 8, 2002, and included 15 730 women.Semi-annual monitoring and outcomes ascertainment continued per trial protocol. The primary end points were coronary heart disease and invasive breast cancer. A global index summarizing the balance of risks and benefits included the 2 primary end points plus stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture, and death due to other causes.The risk of cardiovascular events after the intervention was comparable by initial randomized assignments, 1.97% (annualized rate) in the CEE plus MPA (343 events) and 1.91% in the placebo group (323 events). A greater risk of malignancies occurred in the CEE plus MPA than in the placebo group (1.56% [n = 281] vs 1.26% [n = 218]; hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.04-1.48). More breast cancers were diagnosed in women who had been randomly assigned to receive CEE plus MPA vs placebo (0.42% [n = 79] vs 0.33% [n = 60]; HR, 1.27; 95% CI, 0.91-1.78) with a modest trend toward a lower HR during the follow-up after the intervention. All-cause mortality was somewhat higher in the CEE plus MPA than in the placebo group (1.20% [n = 233] vs 1.06% [n = 196]; HR, 1.15; 95% CI, 0.95-1.39). The global index of risks and benefits was unchanged from randomization through March 31, 2005 (HR, 1.12; 95% CI, 1.03-1.21), indicating that the risks of CEE plus MPA exceed the benefits for chronic disease prevention.The increased cardiovascular risks in the women assigned to CEE plus MPA during the intervention period were not observed after the intervention. A greater risk of fatal and nonfatal malignancies occurred after the intervention in the CEE plus MPA group and the global risk index was 12% higher in women randomly assigned to receive CEE plus MPA compared with placebo.clinicaltrials.gov Identifier: NCT00000611.

    View details for Web of Science ID 000253644800021

    View details for PubMedID 18319414

  • Reproductive steroid hormones and recurrence-free survival in women with a history of breast cancer CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Rock, C. L., Flatt, S. W., Laughlin, G. A., Gold, E. B., Thomson, C. A., Natarajan, L., Jones, L. A., Caan, B. J., Stefanick, M. L., Hajek, R. A., Al-Delaimyl, W. K., Stanczyk, F. Z., Pierce, J. P. 2008; 17 (3): 614-620

    Abstract

    Epidemiologic studies fairly consistently show in postmenopausal women that reproductive steroid hormones contribute to primary breast cancer risk, and this association is strongly supported by experimental studies using laboratory animals and model systems. Evidence linking sex hormone concentrations with risk for recurrence in women diagnosed with breast cancer is limited; however, beneficial effects of antiestrogenic therapy on recurrence-free survival suggest that these hormones affect progression and risk for recurrence. This study examined whether baseline serum concentrations of estradiol, testosterone, and sex hormone binding globulin were associated with recurrence-free survival in a nested case-control cohort of women from a randomized diet trial (Women's Healthy Eating and Living Study) who were followed for >7 years after diagnosis. In 153 case-control pairs of perimenopausal and postmenopausal women in this analysis, total estradiol [hazard ratio (HR), 1.41 per unit increase in log concentration; 95% confidence interval (95% CI), 1.01-1.97], bioavailable estradiol (HR, 1.26; 95% CI, 1.03-1.53), and free estradiol (HR, 1.31; 95% CI, 1.03-1.65) concentrations were significantly associated with risk for recurrence. Recurred women had an average total estradiol concentration that was double that of nonrecurred women (22.7 versus 10.8 pg/mL; P = 0.05). Testosterone and sex hormone binding globulin concentrations did not differ between cases and controls and were not associated with risk for recurrence. Although genetic and metabolic factors likely modulate the relationship between circulating sex hormones and risk, results from this study provide evidence that higher serum estrogen concentration contributes to risk for recurrence in women diagnosed with early stage breast cancer.

    View details for DOI 10.1158/1055-9965.EPI-07-0761

    View details for Web of Science ID 000254373600020

    View details for PubMedID 18323413

  • Factors associated with 5-year risk of hip fracture in postmenopausal women JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Robbins, J., Aragaki, A. K., Kooperberg, C., Watts, N., Wactawski-Wende, J., Jackson, R. D., LeBoff, M. S., Lewis, C. E., Chen, Z., Stefanick, M. L., Cauley, J. 2007; 298 (20): 2389-2398

    Abstract

    The 329,000 hip fractures that annually occur in the United States are associated with high morbidity, mortality, and cost. Identification of those at high risk is a step toward prevention.To develop an algorithm to predict the 5-year risk of hip fracture in postmenopausal women.A total of 93,676 women who participated in the observational component of the Women's Health Initiative (WHI), a multiethnic longitudinal study, were used to develop a predictive algorithm based on commonly available clinical features. Selected factors that predicted hip fracture were then validated by 68,132 women who participated in the clinical trial. The model was tested in a subset of 10,750 women who had undergone dual-energy x-ray absorptiometry (DXA) scans for bone mass density assessment.The prediction of centrally adjudicated hip fracture, measured by the area under the receiver operator characteristic (ROC) curves.During a mean (SD) follow-up of 7.6 (1.7) years, 1132 hip fractures were identified among women participating in the observational study (annualized rate, 0.16%), whereas during a mean follow-up of 8.0 (1.7) years, 791 hip fractures occurred among women participating in the clinical trial (annualized rate, 0.14%). Eleven factors predicted hip fracture within 5 years: age, self-reported health, weight, height, race/ethnicity, self-reported physical activity, history of fracture after age 54 years, parental hip fracture, current smoking, current corticosteroid use, and treated diabetes. Receiver operating characteristic curves showed that the algorithm had an area under the curve of 80% (95% confidence interval [CI], 0.77%-0.82%) when tested in the cohort of different women who were in the clinical trial. A simplified point score was developed for the probability of hip fracture. Receiver operating characteristic curves comparing DXA-scan prediction based on a 10% subset of the cohort and the algorithm among those who participated the clinical trial were similar, with an area under the curve of 79% (95% CI, 73%-85%) vs 71% (95% CI, 66%-76%).This algorithm, based on 11 clinical factors, may be useful to predict the 5-year risk of hip fracture among postmenopausal women of various ethnic backgrounds. Further studies are needed to assess the clinical implication of the algorithm in general and specifically to identify treatment benefits.

    View details for Web of Science ID 000251163400019

    View details for PubMedID 18042916

  • Telephone counseling helps maintain long-term adherence to a high-vegetable dietary pattern JOURNAL OF NUTRITION Pierce, J. P., Newman, V. A., Natarajan, L., Flatt, S. W., Al-Delaimy, W. K., Caan, B. J., Emond, J. A., Faerber, S., Gold, E. B., Hajek, R. A., Hollenbach, K., Jones, L. A., Karanja, N., Kcaley, S., Madlensky, L., Marshall, J., Ritenbaugh, C., Rock, C. L., Stefanick, M. L., Thomson, C., Wasserman, L., Parker, B. A. 2007; 137 (10): 2291-2296

    Abstract

    Achieving long-term adherence to a dietary pattern is a challenge in many studies investigating the relationship between diet and disease. The Women's Healthy Eating and Living Study was a multi-institutional randomized trial in 3088 women at risk for breast cancer recurrence. At baseline, the average participant followed a healthy dietary pattern of 7 vegetable and fruit servings, 21 g/d of fiber, and 28.7% energy from fat, although fat intake increased over the enrollment period. Using primarily telephone counseling, the intervention group was encouraged to substantially increase intakes of vegetables, fruits, and fiber while decreasing fat intake. Sets of 24-h dietary recalls were completed on 90% of eligible participants at 1 y and 86% at 4 y. Using a conservative imputation analysis, at 1 y, the intervention group consumed 38% more vegetable servings (100% when including juice) than the comparison group, 20% more fruit, 38% more fiber, 50% more legumes, and 30% more whole grain foods, with a 20% lower intake of energy from fat. At 4 y, the between-group differences were 65% for vegetables (including juice), 25% fruit, 30% fiber, 40% legumes, 30% whole grain foods, and 13% lower intake of energy from fat. The intervention effect on fat intake was similar for early vs. late enrollees. Plasma carotenoid concentrations on a random 28% sample validated self-reported vegetable and fruit intake, with a between-group difference of 66% at 1 y and over 40% at 4 y. This large change will allow testing of hypotheses on the role of dietary change in preventing additional breast cancer events.

    View details for Web of Science ID 000249701400020

    View details for PubMedID 17885013

  • Prevalence and correlates of sleep-disordered breathing in older men: Osteoporotic fractures in men sleep study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Mehra, R., Stone, K. L., Blackwell, T., Israel, S. A., Dam, T. L., Stefanick, M. L., Redline, S. 2007; 55 (9): 1356-1364

    Abstract

    To determine the prevalence and distribution of sleep-disordered breathing and associated correlates in a large cohort of older men using several standardized definitions.Cross-sectional analyses.Six U.S. communities.Polysomnography was performed on 2,911 participants of the Outcomes of Sleep Disorders in Older Men Sleep Study (mean age+/-standard deviation 76.38+/-5.53; body mass index 27.17+/-3.8 kg/m(2)).Three outcomes were assessed: sleep-disordered breathing (respiratory disturbance index > or =15), obstructive apnea (obstructive apnea index > or =5), and central apnea (central apnea index > or =5).The prevalence of moderate-severe sleep-disordered breathing was estimated to be 21.4% to 26.4%. Multivariable logistic regression models demonstrated that age (adjusted odds ratio (AOR) per 5-year increase =1.24, 95% confidence interval (CI)=1.15-1.34), obesity (AOR=2.54, 95% CI=2.09-3.09), Asian versus Caucasian race (AOR=2.14, 95% CI=1.33-3.45), snoring (AOR=2.01, 95% CI=1.62-2.49), sleepiness (AOR=1.41, 95% CI=1.11-1.79), hypertension (AOR=1.26, 95% CI=1.06-1.50), cardiovascular disease (AOR=1.24, 95% CI=1.19-1.29), and heart failure (AOR=1.81, 1.31-2.51) were independently associated with sleep-disordered breathing; snoring (AOR=2.10, 95% CI=1.67-2.70), age (AOR per 5-year increase=1.27, 95% CI=1.18-1.38), obesity (AOR=1.48, 95% CI=1.21-1.82), and heart failure (AOR=1.60, 95% CI=1.15-2.24) were associated with obstructive apnea; and age (AOR=1.33, 1.17-1.50) and heart failure (AOR=1.88, 95% CI=1.17-3.04) were associated with central apnea.Regardless of definition, a high prevalence of sleep disorders is observed in community-dwelling older men. Qualitatively similar associations were observed between sleep disorders and snoring, obesity, and comorbidities, as reported for middle aged populations. Asian race was associated with sleep-disordered breathing.

    View details for DOI 10.1111/j.1532-5415.2007.01290.x

    View details for Web of Science ID 000249178400005

    View details for PubMedID 17767677

  • Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer - The Women's Healthy Eating and Living (WHEL) Randomized Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Pierce, J. P., Natarajan, L., Caan, B. J., Parker, B. A., Greenberg, E. R., Flatt, S. W., Rock, C. L., Kealey, S., Al-Delaimy, W. K., Bardwell, W. A., Carlson, R. W., Emond, J. A., Faerber, S., Gold, E. B., Hajek, R. A., Hollenbach, K., Jones, L. A., Karanja, N., Madlensky, L., Marshall, J., Newman, V. A., Ritenbaugh, C., Thomson, C. A., Wasserman, L., Stefanick, M. L. 2007; 298 (3): 289-298

    Abstract

    Evidence is lacking that a dietary pattern high in vegetables, fruit, and fiber and low in total fat can influence breast cancer recurrence or survival.To assess whether a major increase in vegetable, fruit, and fiber intake and a decrease in dietary fat intake reduces the risk of recurrent and new primary breast cancer and all-cause mortality among women with previously treated early stage breast cancer.Multi-institutional randomized controlled trial of dietary change in 3088 women previously treated for early stage breast cancer who were 18 to 70 years old at diagnosis. Women were enrolled between 1995 and 2000 and followed up through June 1, 2006.The intervention group (n = 1537) was randomly assigned to receive a telephone counseling program supplemented with cooking classes and newsletters that promoted daily targets of 5 vegetable servings plus 16 oz of vegetable juice; 3 fruit servings; 30 g of fiber; and 15% to 20% of energy intake from fat. The comparison group (n = 1551) was provided with print materials describing the "5-A-Day" dietary guidelines.Invasive breast cancer event (recurrence or new primary) or death from any cause.From comparable dietary patterns at baseline, a conservative imputation analysis showed that the intervention group achieved and maintained the following statistically significant differences vs the comparison group through 4 years: servings of vegetables, +65%; fruit, +25%; fiber, +30%, and energy intake from fat, -13%. Plasma carotenoid concentrations validated changes in fruit and vegetable intake. Throughout the study, women in both groups received similar clinical care. Over the mean 7.3-year follow-up, 256 women in the intervention group (16.7%) vs 262 in the comparison group (16.9%) experienced an invasive breast cancer event (adjusted hazard ratio, 0.96; 95% confidence interval, 0.80-1.14; P = .63), and 155 intervention group women (10.1%) vs 160 comparison group women (10.3%) died (adjusted hazard ratio, 0.91; 95% confidence interval, 0.72-1.15; P = .43). No significant interactions were observed between diet group and baseline demographics, characteristics of the original tumor, baseline dietary pattern, or breast cancer treatment.Among survivors of early stage breast cancer, adoption of a diet that was very high in vegetables, fruit, and fiber and low in fat did not reduce additional breast cancer events or mortality during a 7.3-year follow-up period.clinicaltrials.gov Identifier: NCT00003787.

    View details for Web of Science ID 000248086700023

    View details for PubMedID 17635889

  • Estrogen therapy and coronary-artery calcification NEW ENGLAND JOURNAL OF MEDICINE Manson, J. E., Allison, M. A., Rossouw, J. E., Carr, J. J., Langer, R. D., Hsia, J., Kuller, L. H., Cochrane, B. B., Hunt, J. R., Ludlam, S. E., Pettinger, M. B., Gass, M., Margolis, K. L., Nathan, L., Ockene, J. K., Prentice, R. L., Robbins, J., Stefanick, M. L., Rossouw, J. E., Ludlam, S., Cochrane, B. B., Hunt, J. R., Lund, B., Prentice, R., Carr, J. J., O'Rourke, C., Du, L., Pillsbury, S., Hightower, C., Ellison, R., Tan, J., Wassertheil-Smoller, S., Magnani, M., Noble, D. H., Dellicarpini, T., Manson, J. E., Bueche, M., McGinnis, A. D., Rybicki, F. J., Assaf, A. R., Sloane, G., Phillips, L. S., Butler, V., Huber, M., Vitali, J., Hsia, J., Lebrun, C., Palm, R., Embersit, D., Whitlock, E., Arnold, K., Sidney, S., Cantrell, V., Kotchen, J. M., Feltz, C., Howard, B. V., Thomas-Geevarghese, A., Boggs, G., Jelinick, J. S., Greenland, P., Neuman, A., Carlson-Lund, G., Giovanazzi, S. M., Stefanick, M. L., Swope, S., Jackson, R., Toussant, K., Lewis, C. E., Pierce, P., Stallings, C., Wactawski-Wende, J., Goel, S., Laughlin, R., Robbins, J., Zaragoza, S., Macias, D., BeLisle, D., Nathan, L., Voigt, B., Goldin, J., Woo, M., Langer, R. D., Allison, M. A., Lien, X., Wright, C. M., Gass, M., Sheridan, S., Robinson, J. G., Feddersen, D., Kelly-Brake, K., Carroll, J., Ockene, J., Churchill, L., Lasser, N. L., Miller, B., Maldjian, P. D., Pierre-Louis, J., FISHMAN, J., O'Sullivan, M. J., Fernandez, D., Margolis, K. L., Bjerk, C. L., Truwit, C., Hearity, J. A., Hyslop, W. B., Darroch, K., Murphy, C., Heiss, G., Kuller, L. H., Edmundowicz, D., Ives, D., Johnson, K. C., Satterfield, S., Connelly, S. A., Jones, E. L., Brzyski, R., Nashawati, M. A., Torchia, S., Rodriguez, A., Garza, R., Nentwich, P., Sarto, G. E., Broderick, L., Sweitzer, N. K., Nabel, E., Rossouw, J. E., Ludlam, S. E., Pottern, L., McGowan, J., Ford, L., Geller, N., Prentice, R. L., Anderson, G., Lacroix, A., Kooperberg, C. L., Patterson, R. E., McTiernan, A., Shumaker, S., Stein, E., Cummings, S., Wassertheil-Smoller, S., Hays, J., Manson, J. E., Assaf, A. R., Phillips, L., Beresford, S., Hsia, J., Chlebowski, R., Whitlock, E., Caan, B., Kotchen, J. M., Howard, B. V., Van Horn, L., BLACK, H., Stefanick, M. L., Lane, D., Jackson, R., Lewis, C. E., Bassford, T., Wactawski-Wende, J., Robbins, J., Hubbell, F. A., Judd, H., Langer, R. D., Gass, M., Limacher, M., Curb, D., Wallace, R., Ockene, J., Lasser, N., O'Sullivan, M. J., Margolis, K. L., Brunner, R., Heiss, G., Kuller, L. H., Johnson, K. C., Brzyski, R., Sarto, G. E., Bonds, D., Hendrix, S. 2007; 356 (25): 2591-2602

    Abstract

    Calcified plaque in the coronary arteries is a marker for atheromatous-plaque burden and is predictive of future risk of cardiovascular events. We examined the relationship between estrogen therapy and coronary-artery calcium in the context of a randomized clinical trial.In our ancillary substudy of the Women's Health Initiative trial of conjugated equine estrogens (0.625 mg per day) as compared with placebo in women who had undergone hysterectomy, we performed computed tomography of the heart in 1064 women aged 50 to 59 years at randomization. Imaging was conducted at 28 of 40 centers after a mean of 7.4 years of treatment and 1.3 years after the trial was completed (8.7 years after randomization). Coronary-artery calcium (or Agatston) scores were measured at a central reading center without knowledge of randomization status.The mean coronary-artery calcium score after trial completion was lower among women receiving estrogen (83.1) than among those receiving placebo (123.1) (P=0.02 by rank test). After adjustment for coronary risk factors, the multivariate odds ratios for coronary-artery calcium scores of more than 0, 10 or more, and 100 or more in the group receiving estrogen as compared with placebo were 0.78 (95% confidence interval, 0.58 to 1.04), 0.74 (0.55 to 0.99), and 0.69 (0.48 to 0.98), respectively. The corresponding odds ratios among women with at least 80% adherence to the study estrogen or placebo were 0.64 (P=0.01), 0.55 (P<0.001), and 0.46 (P=0.001). For coronary-artery calcium scores of more than 300 (vs. <10), the multivariate odds ratio was 0.58 (P=0.03) in an intention-to-treat analysis and 0.39 (P=0.004) among women with at least 80% adherence.Among women 50 to 59 years old at enrollment, the calcified-plaque burden in the coronary arteries after trial completion was lower in women assigned to estrogen than in those assigned to placebo. However, estrogen has complex biologic effects and may influence the risk of cardiovascular events and other outcomes through multiple pathways. (ClinicalTrials.gov number, NCT00000611.)

    View details for Web of Science ID 000247351200006

    View details for PubMedID 17582069

  • Greater survival after breast cancer in physically active women with high vegetable-fruit intake regardless of obesity JOURNAL OF CLINICAL ONCOLOGY Pierce, J. P., Stefanick, M. L., Flatt, S. W., Natarajan, L., Sternfeld, B., Madlensky, L., Al-Delaimy, W. K., Thomson, C. A., Kealey, S., Hajek, R., Parker, B. A., Newman, V. A., Caan, B., Rock, C. L. 2007; 25 (17): 2345-2351

    Abstract

    Single-variable analyses have associated physical activity, diet, and obesity with survival after breast cancer. This report investigates interactions among these variables.A prospective study was performed of 1,490 women diagnosed and treated for early-stage breast cancer between 1991 and 2000. Enrollment was an average of 2 years postdiagnosis. Only seven women were lost to follow-up through December 2005.In univariate analysis, reduced mortality was weakly associated with higher vegetable-fruit consumption, increased physical activity, and a body mass index that was neither low weight nor obese. In a multivariate Cox model, only the combination of consuming five or more daily servings of vegetables-fruits, and accumulating 540+ metabolic equivalent tasks-min/wk (equivalent to walking 30 minutes 6 d/wk), was associated with a significant survival advantage (hazard ratio, 0.56; 95% CI, 0.31 to 0.98). The approximate 50% reduction in risk associated with these healthy lifestyle behaviors was observed in both obese and nonobese women, although fewer obese women were physically active with a healthy dietary pattern (16% v 30%). Among those who adhered to this healthy lifestyle, there was no apparent effect of obesity on survival. The effect was stronger in women who had hormone receptor-positive cancers.A minority of breast cancer survivors follow a healthy lifestyle that includes both recommended intakes of vegetables-fruits and moderate levels of physical activity. The strong protective effect observed suggests a need for additional investigation of the effect of the combined influence of diet and physical activity on breast cancer survival.

    View details for DOI 10.1200/JCO.2006.08.6819

    View details for Web of Science ID 000247241600005

    View details for PubMedID 17557947

  • Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Rossouw, J. E., Prentice, R. L., Manson, J. E., Wu, L., Barad, D., Barnabei, V. M., Ko, M., LaCroix, A. Z., Margolis, K. L., Stefanick, M. L. 2007; 297 (13): 1465-1477

    Abstract

    The timing of initiation of hormone therapy may influence its effect on cardiovascular disease.To explore whether the effects of hormone therapy on risk of cardiovascular disease vary by age or years since menopause began.Secondary analysis of the Women's Health Initiative (WHI) randomized controlled trials of hormone therapy in which 10,739 postmenopausal women who had undergone a hysterectomy were randomized to conjugated equine estrogens (CEE) or placebo and 16,608 postmenopausal women who had not had a hysterectomy were randomized to CEE plus medroxyprogesterone acetate (CEE + MPA) or placebo. Women aged 50 to 79 years were recruited to the study from 40 US clinical centers between September 1993 and October 1998.Statistical test for trend of the effect of hormone therapy on coronary heart disease (CHD) and stroke across categories of age and years since menopause in the combined trials.In the combined trials, there were 396 cases of CHD and 327 cases of stroke in the hormone therapy group vs 370 [corrected] cases of CHD and 239 cases of stroke in the placebo group. For women with less than 10 years since menopause began, the hazard ratio (HR) for CHD was 0.76 (95% confidence interval [CI], 0.50-1.16); 10 to 19 years, 1.10 (95% CI, 0.84-1.45); and 20 or more years, 1.28 (95% CI, 1.03-1.58) (P for trend = .02). The estimated absolute excess risk for CHD for women within 10 years of menopause was -6 per 10,000 person-years; for women 10 to 19 years since menopause began, 4 per 10,000 person-years; and for women 20 or more years from menopause onset, 17 per 10,000 person-years. For the age group of 50 to 59 years, the HR for CHD was 0.93 (95% CI, 0.65-1.33) and the absolute excess risk was -2 per 10,000 person-years; 60 to 69 years, 0.98 (95% CI, 0.79-1.21) and -1 per 10,000 person-years; and 70 to 79 years, 1.26 (95% CI, 1.00-1.59) and 19 per 10,000 person-years (P for trend = .16). Hormone therapy increased the risk of stroke (HR, 1.32; 95% CI, 1.12-1.56). Risk did not vary significantly by age or time since menopause. There was a nonsignificant tendency for the effects of hormone therapy on total mortality to be more favorable in younger than older women (HR of 0.70 for 50-59 years; 1.05 for 60-69 years, and 1.14 for 70-79 years; P for trend = .06).Women who initiated hormone therapy closer to menopause tended to have reduced CHD risk compared with the increase in CHD risk among women more distant from menopause, but this trend test did not meet our criterion for statistical significance. A similar nonsignificant trend was observed for total mortality but the risk of stroke was elevated regardless of years since menopause. These data should be considered in regard to the short-term treatment of menopausal symptoms.clinicaltrials.gov Identifier: NCT00000611.

    View details for Web of Science ID 000245404100023

    View details for PubMedID 17405972

  • Endogenous sex steroids, weight change and rates of hip bone loss in older men: the MrOS study OSTEOPOROSIS INTERNATIONAL Ensrud, K. E., Lewis, C. E., Lambert, L. C., Taylor, B. C., Fink, H. A., Barrett-Connor, E., Cauley, J. A., Stefanick, M. L., Orwoll, E. 2006; 17 (9): 1329-1336

    Abstract

    Lower levels of endogenous sex steroids or declines in these hormones may contribute to the increased rates of bone loss observed in older adults experiencing weight loss. We hypothesized that among older men with weight loss, higher rates of bone loss at the hip would be observed in men with lower baseline bioavailable sex steroids or those with greater declines in these hormones.To test this hypothesis, body weight, hip bone mineral density (BMD) using dual energy x-ray absorptiometry and endogenous sex steroids in paired serum samples by sensitive immunoassays were measured at a baseline and at a second examination that was held an average of 1.8 years later in 1267 older men enrolled in the Osteoporotic Fractures in Men (MrOS) study.Men experiencing weight loss had higher rates of hip bone loss than those with stable weight or weight gain within each quartile of baseline sex steroid level [p values for test of trend across weight change categories <0.010 within each quartile of bioavailable estradiol and testosterone and <0.060 within each quartile of sex hormone-binding globulin (SHBG)]. Results were similar when a change in sex steroids was substituted for baseline sex steroids in the analyses. Among men with weight loss, the rate of decline in total hip BMD showed a stepwise increase in magnitude with decreasing baseline bioavailable estradiol (p value for trend <0.040), with increasing baseline SHBG (p value for trend<0.030) and with greater decreases in bioavailable testosterone from baseline (p value for trend <0.001).These findings support the hypothesis that the impact of weight loss in older men on rates of hip bone loss may be increased by the presence of a sex steroid insufficiency.

    View details for DOI 10.1007/s00198-006-0088-z

    View details for Web of Science ID 000239300400002

    View details for PubMedID 16767524

  • Post-diagnosis weight gain and breast cancer recurrence in women with early stage breast cancer BREAST CANCER RESEARCH AND TREATMENT Caan, B. J., Emond, J. A., Natarajan, L., Castillo, A., Gunderson, E. P., Habel, L., Jones, L., Newman, V. A., Rock, C. L., Slattery, M. L., Stefanick, M. L., Sternfeld, B., Thomson, C. A., Pierce, J. P. 2006; 99 (1): 47-57

    Abstract

    To examine whether weight gain after diagnosis of breast cancer affects the risk of breast cancer recurrence.Patients included 3215 women diagnosed with early stage breast cancer (Stage I >1 cm., II, and IIIA) who were enrolled either in an observational cohort of breast cancer survivors or were part of the comparison group of a dietary intervention trial to prevent breast cancer recurrence. We computed weight change from 1 year prior to diagnosis to study enrollment. Delayed entry Cox proportional hazards models were used to evaluate associations of categories of weight change with time to recurrence, controlling for known prognostic factors.Neither moderate (5-10%) nor large (> 10%) weight gain (HR 0.8, 95% CI, 0.6-1.1; HR 0.9, 95% CI, 0.7-1.2, respectively) after breast cancer diagnosis was associated with an increased risk of breast cancer recurrence in the early years post-diagnosis (median time of 73.7 months from diagnosis).Our research provides evidence that weight gain commonly seen in the first several years following a breast cancer diagnosis does not increase a woman's risk for breast cancer recurrence in the first 5-7 years post-diagnosis. However, this research does not address the effects of weight gain on overall survival or on the risk of other new cancers, other prognostic outcomes of concern to the breast cancer survivor.

    View details for DOI 10.1007/s10549-006-9179-y

    View details for Web of Science ID 000239548500006

    View details for PubMedID 16541317

  • Risk-benefit profiles of raloxifene for women NEW ENGLAND JOURNAL OF MEDICINE Stefanick, M. L. 2006; 355 (2): 190-192

    View details for Web of Science ID 000238970600013

    View details for PubMedID 16837684

  • Mortality and cardiac and vascular outcomes in extremely obese women JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION McTigue, K., Larson, J. C., Valoski, A., Burke, G., Kotchen, J., Lewis, C. E., Stefanick, M. L., Van Horn, L., Kuller, L. 2006; 296 (1): 79-86

    Abstract

    Obesity, typically measured as body mass index of 30 or higher, has 3 subclasses: obesity 1 (30-34.9); obesity 2 (35-39.9); and extreme obesity (> or =40). Extreme obesity is increasing particularly rapidly in the United States, yet its health risks are not well characterized.To determine how cardiovascular and mortality risks differ across clinical weight categories in women, with a focus on extreme obesity.We examined incident mortality and cardiovascular outcomes by weight status in 90,185 women recruited from 40 US centers for the Women's Health Initiative Observational Study and followed up for an average of 7.0 years (October 1, 1993 to August 31, 2004).Incidence of mortality, coronary heart disease, diabetes, and hypertension.Extreme obesity prevalence differed with race/ethnicity, from 1% among Asian and Pacific Islanders to 10% among black women. All-cause mortality rates per 10,000 person-years were 68.39 (95% confidence interval [CI], 65.26-71.68) for normal body mass index, 71.16 (95% CI, 67.68-74.82) for overweight, 84.47 (95% CI, 78.90-90.42) for obesity 1, 102.85 (95% CI, 92.90-113.86) for obesity 2, and 116.85 (95% CI, 103.36-132.11) for extreme obesity. Analyses adjusted for age, smoking, educational achievement, US region, and physical activity levels showed that weight-related risk for all-cause mortality, coronary heart disease mortality, and coronary heart disease incidence did not differ by race/ethnicity. Adjusted analyses among white and black participants showed positive trends in all-cause mortality and coronary heart disease incidence with increasing weight category. Much of the obesity-related mortality and coronary heart disease risk was mediated by diabetes, hypertension, and hyperlipidemia. In white women, weight-related all-cause mortality risk was modified by age, with obesity conferring less risk among older women.Considering obesity as a body mass index of 30 or higher may lead to misinterpretation of individual and population risks. Escalating extreme obesity may exacerbate health effects and costs of the obesity epidemic.

    View details for Web of Science ID 000238683100025

    View details for PubMedID 16820550

  • Dietary factors and vasomotor symptoms in breast cancer survivors: the WHEL Study MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Gold, E. B., Flatt, S. W., Pierce, J. P., Bardwell, W. A., Hajek, R. A., Newman, V. A., Rock, C. L., Stefanick, M. L. 2006; 13 (3): 423-433

    Abstract

    Vasomotor symptoms (VMS)(hot flashes, night sweats) are associated with natural or surgically or chemotherapy-induced menopause, the latter occurring frequently in women treated for breast cancer. To manage VMS, some women seek alternatives to menopausal hormone therapy, such as supplements or modified food choices. The objective of the present analyses was to assess associations of VMS occurrence and change in severity of VMS over 12 months with dietary intakes of fiber, fat, and selected soy-containing foods, and use of phytoestrogen or vitamin E supplements in women with recent early stage breast cancer, adjusting for covariates.Using multivariate logistic regression, data were analyzed from 2,198 women with early-stage breast cancer who enrolled 2 to 48 months after diagnosis in the Women's Healthy Eating and Living randomized, controlled trial of a high-vegetable, high-fiber, reduced-fat diet.Being peri- or postmenopausal, using tamoxifen, having low social support or depressive symptoms, and using vitamin E or phytoestrogen supplements were significantly associated cross-sectionally with reporting moderate/severe VMS at enrollment. Increased symptom severity after 12 months was significantly associated with higher body mass index, tamoxifen use, and smoking. Decreased symptom severity at 12 months was significantly associated with high dietary fiber intake; no decrease was observed in women who were peri- or postmenopausal, using tamoxifen, or had low fat intake or low social support.High dietary fiber intakes, premenopausal, and high social support were related to decreased severity of VMS 1 year after study enrollment in women recently treated for breast cancer.

    View details for DOI 10.1097/01.gme.0000185754.85328.44

    View details for Web of Science ID 000238116100013

    View details for PubMedID 16735939

  • Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Stefanick, M. L., Anderson, G. L., Margolis, K. L., Hendrix, S. L., Rodabough, R. J., Paskett, E. D., Lane, D. S., Hubbell, F. A., Assaf, A. R., Sarto, G. E., Schenken, R. S., Yasmeen, S., Lessin, L., Chlebowski, R. T. 2006; 295 (14): 1647-1657

    Abstract

    The Women's Health Initiative Estrogen-Aone trial comparing conjugated equine estrogens (CEE) with placebo was stopped early because of an increased stroke incidence and no reduction in risk of coronary heart disease. Preliminary results suggesting possible reduction in breast cancers warranted more detailed analysis.To determine the effects of CEE on breast cancers and mammographic findings.Following breast cancer risk assessment, 10,739 postmenopausal women aged 50 to 79 years with prior hysterectomy were randomized to CEE or placebo at 40 US clinical centers from 1993 through 1998. Mammography screenings and clinical breast examinations were performed at baseline and annually. All breast cancers diagnosed through February 29, 2004, are included.A dose of 0.625 mg/d of CEE or an identical-appearing placebo.Breast cancer incidence, tumor characteristics, and mammogram findings.After a mean (SD) follow-up of 7.1 (1.6) years, the invasive breast cancer hazard ratio (HR) for women assigned to CEE vs placebo was 0.80 (95% confidence interval [CI], 0.62-1.04; P = .09) with annualized rates of 0.28% (104 cases in the CEE group) and 0.34% (133 cases in the placebo group). In exploratory analyses, ductal carcinomas (HR, 0.71; 95% CI, 0.52-0.99) were reduced in the CEE group vs placebo group; however, the test for interaction by tumor type was not significant (P = .054). At 1 year, 9.2% of women in the CEE group had mammograms with abnormalities requiring follow-up vs 5.5% in the placebo group (P<.001), a pattern that continued through the trial to reach a cumulative percentage of 36.2% vs 28.1%, respectively (P<.001); however, this difference was primarily in assessments requiring short interval follow-up.Treatment with CEE alone for 7.1 years does not increase breast cancer incidence in postmenopausal women with prior hysterectomy. However, treatment with CEE increases the frequency of mammography screening requiring short interval follow-up. Initiation of CEE should be based on consideration of the individual woman's potential risks and benefits.clinicaltrials.gov Identifier: NCT00000611.

    View details for Web of Science ID 000236707300020

    View details for PubMedID 16609086

  • Combined analysis of Women's Health Initiative Observational and Clinical Trial data on postmenopausal hormone treatment and cardiovascular disease AMERICAN JOURNAL OF EPIDEMIOLOGY Prentice, R. L., Langer, R. D., Stefanick, M. L., Howard, B. V., Pettinger, M., Anderson, G. L., Barad, D., Curb, J. D., Kotchen, J., Kuller, L., Limacher, M., Wactawski-Wende, J. 2006; 163 (7): 589-599

    Abstract

    Circumstances in which both randomized controlled trial and observational study data are available provide an important opportunity to identify biases and improve study design and analysis procedures. In addition, joint analyses of data from the two sources can extend clinical trial findings. The US Women's Health Initiative includes randomized controlled trials of use of estrogen by posthysterectomy women and of estrogen plus progestin by women with a uterus, along with corresponding observational study components. In this paper, for coronary heart disease, stroke, and venous thromboembolism, results are first presented from joint analysis of estrogen clinical trial and observational study data to show that residual bias patterns are similar to those previously reported for estrogen plus progestin. These findings support certain combined analyses of the observational data on estrogen and the estrogen plus progestin clinical trial and observational study data to give adjusted observational study estimates of estrogen treatment effects. The resulting treatment effect estimates are compared with corresponding clinical trial estimates, and parallel analyses are also presented for estrogen plus progestin. An application to postmenopausal hormone treatment effects on coronary heart disease among younger women is also provided.

    View details for DOI 10.1093/aje/kwj079

    View details for Web of Science ID 000236250900001

    View details for PubMedID 16484450

  • Obesity, hormone therapy, estrogen metabolism and risk of postmenopausal breast cancer INTERNATIONAL JOURNAL OF CANCER Modugno, F., Kip, K. E., Cochrane, B., Kuller, L., Klug, T. L., Rohan, T. E., Chlebowski, R. T., Lasser, N., Stefanick, M. L. 2006; 118 (5): 1292-1301

    Abstract

    Hormone therapy (HT) and body mass index (BMI) have been associated with postmenopausal breast cancer. Because estrogen metabolism may affect breast cancer risk and can be altered by weight and HT, it might play a role in the HT-BMI-breast cancer associations. We undertook a nested case-control study within the Observational Study of the Women's Health Initiative. Baseline levels of 2- and 16alpha-hydroxy estrone (2-OHE1 and 16alpha-OHE1) were measured in 200 women who developed breast cancer during follow-up and 200 healthy controls matched to cases by ethnicity, enrollment date, clinic site, type of HT and years since menopause. Wilcoxon nonparametric tests were used to compare estrogen metabolite levels between cases and controls. Conditional logistic regression was used to assess the relationship between BMI, estrogen metabolites and breast cancer risk. 16alpha-OHE1 levels were modestly but significantly higher in HT users among cases (median 356 pg/ml vs. 315 pg/ml) and controls (354 pg/ml vs. 298 pg/ml). 2-OHE1 levels were substantially and significantly higher in HT users among cases (369 pg/ml vs. 125 pg/ml) and controls (347 pg/ml vs. 134 pg/ml). For non-HT users only, greater BMI and higher 16alpha-OHE1 levels were individually and jointly associated with increased breast cancer risk (OR for women with high BMI and high 16alpha-OHE1 compared to those with low BMI and low 16alpha-OHE1 = 3.51, 95% CI = 1.34-9.16). No associations between BMI, estrogen metabolism and breast cancer risk were found for HT users. Estrogen metabolism differs according to both BMI and HT use, potentially explaining the interaction between BMI and HT in relation to breast cancer risk.

    View details for DOI 10.1002/ijc.21487

    View details for Web of Science ID 000235056100029

    View details for PubMedID 16161054

  • Calcium plus vitamin D supplementation and the risk of colorectal cancer NEW ENGLAND JOURNAL OF MEDICINE Wactawski-Wende, J., Kotchen, J. M., Anderson, G. L., Assaf, A. R., Brunner, R. L., O'Sullivan, M. J., Margolis, K. L., Ockene, J. K., Phillips, L., Pottern, L., Prentice, R. L., Robbins, J., Rohan, T. E., Sarto, G. E., Sharma, S., Stefanick, M. L., Van Horn, L., Wallace, R. B., Whitlock, E., Bassford, T., Beresford, S. A., Black, H. R., Bonds, D. E., Brzyski, R. G., Caan, B., Chlebowski, R. T., Cochrane, B., Garland, C., Gass, M., Hays, J., Heiss, G., Hendrix, S. L., Howard, B. V., Hsia, J., Hubbell, F. A., Jackson, R. D., Johnson, K. C., Judd, H., Kooperberg, C. L., Kuller, L. H., LaCroix, A. Z., Lane, D. S., Langer, R. D., Lasser, N. L., Lewis, C. E., Limacher, M. C., Manson, J. E. 2006; 354 (7): 684-696

    Abstract

    Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking.We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women's Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [corrected] twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.0 years. The incidence of pathologically confirmed colorectal cancer was the designated secondary outcome. Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study.The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P=0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics.Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention. (ClinicalTrials.gov number, NCT00000611.).

    View details for Web of Science ID 000235316100005

    View details for PubMedID 16481636

  • Calcium plus vitamin D supplementation and the risk of fractures NEW ENGLAND JOURNAL OF MEDICINE Jackson, R. D., LaCroix, A. Z., Gass, M., Wallace, R. B., Robbins, J., Lewis, C. E., Bassford, T., Beresford, S. A., Black, H. R., Blanchette, P., Bonds, D. E., Brunner, R. L., Brzyski, R. G., Caan, B., Cauley, J. A., Chlebowski, R. T., Cummings, S. R., Granek, I., Hays, J., Heiss, G., Hendrix, S. L., Howard, B. V., Hsia, J., Hubbell, F. A., Johnson, K. C., Judd, H., Kotchen, J. M., Kuller, L. H., Langer, R. D., Lasser, N. L., Limacher, M. C., Ludlam, S., Manson, J. E., Margolis, K. L., McGowan, J., Ockene, J. K., O'Sullivan, M. J., Phillips, L., Prentice, R. L., Sarto, G. E., Stefanick, M. L., Van Horn, L., Wactawski-Wende, J., Whitlock, E., Anderson, G. L., Assaf, A. R., Barad, D. 2006; 354 (7): 669-683

    Abstract

    The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal.We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental [corrected] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers.Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels.Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.).

    View details for Web of Science ID 000235316100004

    View details for PubMedID 16481635

  • Low-fat dietary pattern and risk of invasive breast cancer - The women's health initiative randomized controlled dietary modification trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Prentice, R. L., Caan, B., Chlebowski, R. T., Patterson, R., Kuller, L. H., Ockene, J. K., Margolis, K. L., Limacher, M. C., Manson, J. E., Parker, L. M., Paskett, E., Phillips, L., Robbins, J., Rossouw, J. E., Sarto, G. E., Shikany, J. M., Stefanick, M. L., Thomson, C. A., Van Horn, L., Vitolins, M. Z., Wactawski-Wende, J., Wallace, R. B., Wassertheil-Smoller, S., Whitlock, E., Yano, K., Adams-Campbell, L., Anderson, G. L., Assaf, A. R., Beresford, S. A., Black, H. R., Brunner, R. L., Brzyski, R. G., Ford, L., Gass, M., Hays, J., Heber, D., Heiss, G., Hendrix, S. L., Hsia, J., Hubbell, F. A., Jackson, R. D., Johnson, K. C., Kotchen, J. M., LaCroix, A. Z., Lane, D. S., Langer, R. D., Lasser, N. L., Henderson, M. M. 2006; 295 (6): 629-642

    Abstract

    The hypothesis that a low-fat dietary pattern can reduce breast cancer risk has existed for decades but has never been tested in a controlled intervention trial.To assess the effects of undertaking a low-fat dietary pattern on breast cancer incidence.A randomized, controlled, primary prevention trial conducted at 40 US clinical centers from 1993 to 2005.A total of 48,835 postmenopausal women, aged 50 to 79 years, without prior breast cancer, including 18.6% of minority race/ethnicity, were enrolled.Women were randomly assigned to the dietary modification intervention group (40% [n = 19,541]) or the comparison group (60% [n = 29,294]). The intervention was designed to promote dietary change with the goals of reducing intake of total fat to 20% of energy and increasing consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily. Comparison group participants were not asked to make dietary changes.Invasive breast cancer incidence.Dietary fat intake was significantly lower in the dietary modification intervention group compared with the comparison group. The difference between groups in change from baseline for percentage of energy from fat varied from 10.7% at year 1 to 8.1% at year 6. Vegetable and fruit consumption was higher in the intervention group by at least 1 serving per day and a smaller, more transient difference was found for grain consumption. The number of women who developed invasive breast cancer (annualized incidence rate) over the 8.1-year average follow-up period was 655 (0.42%) in the intervention group and 1072 (0.45%) in the comparison group (hazard ratio, 0.91; 95% confidence interval, 0.83-1.01 for the comparison between the 2 groups). Secondary analyses suggest a lower hazard ratio among adherent women, provide greater evidence of risk reduction among women having a high-fat diet at baseline, and suggest a dietary effect that varies by hormone receptor characteristics of the tumor.Among postmenopausal women, a low-fat dietary pattern did not result in a statistically significant reduction in invasive breast cancer risk over an 8.1-year average follow-up period. However, the nonsignificant trends observed suggesting reduced risk associated with a low-fat dietary pattern indicate that longer, planned, nonintervention follow-up may yield a more definitive comparison.ClinicalTrials.gov Identifier: NCT00000611.

    View details for Web of Science ID 000235168200023

    View details for PubMedID 16467232

  • Low-fat dietary pattern and risk of cardiovascular disease - The Women's Health Initiative randomized controlled dietary modification trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Howard, B. V., Van Horn, L., Hsia, J., Manson, J. E., Stefanick, M. L., Wassertheil-Smoller, S., Kuller, L. H., LaCroix, A. Z., Langer, R. D., Lasser, N. L., Lewis, C. E., Limacher, M. C., Margolis, K. L., Mysiw, J., Ockene, J. K., Parker, L. M., Perri, M. G., Phillips, L., Prentice, R. L., Robbins, J., Rossouw, J. E., Sarto, G. E., Schatz, I. J., Snetselaar, L. G., Stevens, V. J., Tinker, L. F., Trevisan, M., Vitolins, M. Z., Anderson, G. L., Assaf, A. R., Bassford, T., Beresford, S. A., Black, H. R., Brunner, R. L., Brzyski, R. G., Caan, B., Chlebowski, R. T., Gass, M., Granek, I., Greenland, P., Hays, J., Heber, D., Heiss, G., Hendrix, S. L., Hubbell, F. A., Johnson, K. C., Kotchen, J. M. 2006; 295 (6): 655-666

    Abstract

    Multiple epidemiologic studies and some trials have linked diet with cardiovascular disease (CVD) prevention, but long-term intervention data are needed.To test the hypothesis that a dietary intervention, intended to be low in fat and high in vegetables, fruits, and grains to reduce cancer, would reduce CVD risk.Randomized controlled trial of 48,835 postmenopausal women aged 50 to 79 years, of diverse backgrounds and ethnicities, who participated in the Women's Health Initiative Dietary Modification Trial. Women were randomly assigned to an intervention (19,541 [40%]) or comparison group (29,294 [60%]) in a free-living setting. Study enrollment occurred between 1993 and 1998 in 40 US clinical centers; mean follow-up in this analysis was 8.1 years.Intensive behavior modification in group and individual sessions designed to reduce total fat intake to 20% of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d. The comparison group received diet-related education materials.Fatal and nonfatal coronary heart disease (CHD), fatal and nonfatal stroke, and CVD (composite of CHD and stroke).By year 6, mean fat intake decreased by 8.2% of energy intake in the intervention vs the comparison group, with small decreases in saturated (2.9%), monounsaturated (3.3%), and polyunsaturated (1.5%) fat; increases occurred in intakes of vegetables/fruits (1.1 servings/d) and grains (0.5 serving/d). Low-density lipoprotein cholesterol levels, diastolic blood pressure, and factor VIIc levels were significantly reduced by 3.55 mg/dL, 0.31 mm Hg, and 4.29%, respectively; levels of high-density lipoprotein cholesterol, triglycerides, glucose, and insulin did not significantly differ in the intervention vs comparison groups. The numbers who developed CHD, stroke, and CVD (annualized incidence rates) were 1000 (0.63%), 434 (0.28%), and 1357 (0.86%) in the intervention and 1549 (0.65%), 642 (0.27%), and 2088 (0.88%) in the comparison group. The diet had no significant effects on incidence of CHD (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.90-1.06), stroke (HR, 1.02; 95% CI, 0.90-1.15), or CVD (HR, 0.98; 95% CI, 0.92-1.05). Excluding participants with baseline CVD (3.4%), the HRs (95% CIs) for CHD and stroke were 0.94 (0.86-1.02) and 1.02 (0.90-1.17), respectively. Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits.Over a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk.ClinicalTrials.gov Identifier: NCT00000611.

    View details for Web of Science ID 000235168200025

    View details for PubMedID 16467234

  • Low-fat dietary pattern and risk of colorectal cancer - The Women's Health Initiative randomized controlled dietary modification trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Beresford, S. A., Johnson, K. C., Ritenbaugh, C., Lasser, N. L., Snetselaar, L. G., Black, H. R., Anderson, G. L., Assaf, A. R., Bassford, T., Bowen, D., Brunner, R. L., Brzyski, R. G., Caan, B., Chlebowski, R. T., Gass, M., Harrigan, R. C., Hays, J., Heber, D., Heiss, G., Hendrix, S. L., Howard, B. V., Hsia, J., Hubbell, F. A., Jackson, R. D., Kotchen, J. M., Kuller, L. H., LaCroix, A. Z., Lane, D. S., Langer, R. D., Lewis, C. E., Manson, J. E., Margolis, K. L., Mossavar-Rahmani, Y., Ockene, J. K., Parker, L. M., Perri, M. G., Phillips, L., Prentice, R. L., Robbins, J., Rossouw, J. E., Sarto, G. E., Stefanick, M. L., Van Horn, L., Vitolins, M. Z., Wactawski-Wende, J., Wallace, R. B., Whitlock, E. 2006; 295 (6): 643-654

    Abstract

    Observational studies and polyp recurrence trials are not conclusive regarding the effects of a low-fat dietary pattern on risk of colorectal cancer, necessitating a primary prevention trial.To evaluate the effects of a low-fat eating pattern on risk of colorectal cancer in postmenopausal women.The Women's Health Initiative Dietary Modification Trial, a randomized controlled trial conducted in 48,835 postmenopausal women aged 50 to 79 years recruited between 1993 and 1998 from 40 clinical centers throughout the United States.Participants were randomly assigned to the dietary modification intervention (n = 19,541; 40%) or the comparison group (n = 29,294; 60%). The intensive behavioral modification program aimed to motivate and support reductions in dietary fat, to increase consumption of vegetables and fruits, and to increase grain servings by using group sessions, self-monitoring techniques, and other tailored and targeted strategies. Women in the comparison group continued their usual eating pattern.Invasive colorectal cancer incidence.A total of 480 incident cases of invasive colorectal cancer occurred during a mean follow-up of 8.1 (SD, 1.7) years. Intervention group participants significantly reduced their percentage of energy from fat by 10.7% more than did the comparison group at 1 year, and this difference between groups was mostly maintained (8.1% at year 6). Statistically significant increases in vegetable, fruit, and grain servings were also made. Despite these dietary changes, there was no evidence that the intervention reduced the risk of invasive colorectal cancer during the follow-up period. There were 201 women with invasive colorectal cancer (0.13% per year) in the intervention group and 279 (0.12% per year) in the comparison group (hazard ratio, 1.08; 95% confidence interval, 0.90-1.29). Secondary analyses suggested potential interactions with baseline aspirin use and combined estrogen-progestin use status (P = .01 for each). Colorectal examination rates, although not protocol defined, were comparable between the intervention and comparison groups. Similar results were seen in analyses adjusting for adherence to the intervention.In this study, a low-fat dietary pattern intervention did not reduce the risk of colorectal cancer in postmenopausal women during 8.1 years of follow-up.ClinicalTrials.gov Identifier: NCT00000611.

    View details for Web of Science ID 000235168200024

    View details for PubMedID 16467233

  • Low-fat dietary pattern and weight change over 7 years - The Women's Health Initiative Dietary Modification Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Howard, B. V., Manson, J. E., Stefanick, M. L., Beresford, S. A., Frank, G., Jones, B. T., Rodabough, R. J., Snetselaar, L., Thomson, C., Tinker, L., Vitolins, M., Prentice, R. 2006; 295 (1): 39-49

    Abstract

    Obesity in the United States has increased dramatically during the past several decades. There is debate about optimum calorie balance for prevention of weight gain, and proponents of some low-carbohydrate diet regimens have suggested that the increasing obesity may be attributed, in part, to low-fat, high-carbohydrate diets.To report data on body weight in a long-term, low-fat diet trial for which the primary end points were breast and colorectal cancer and to examine the relationships between weight changes and changes in dietary components.Randomized intervention trial of 48,835 postmenopausal women in the United States who were of diverse backgrounds and ethnicities and participated in the Women's Health Initiative Dietary Modification Trial; 40% (19,541) were randomized to the intervention and 60% (29,294) to a control group. Study enrollment was between 1993 and 1998, and this analysis includes a mean follow-up of 7.5 years (through August 31, 2004).The intervention included group and individual sessions to promote a decrease in fat intake and increases in vegetable, fruit, and grain consumption and did not include weight loss or caloric restriction goals. The control group received diet-related education materials.Change in body weight from baseline to follow-up.Women in the intervention group lost weight in the first year (mean of 2.2 kg, P<.001) and maintained lower weight than control women during an average 7.5 years of follow-up (difference, 1.9 kg, P<.001 at 1 year and 0.4 kg, P = .01 at 7.5 years). No tendency toward weight gain was observed in intervention group women overall or when stratified by age, ethnicity, or body mass index. Weight loss was greatest among women in either group who decreased their percentage of energy from fat. A similar but lesser trend was observed with increases in vegetable and fruit servings, and a nonsignificant trend toward weight loss occurred with increasing intake of fiber.A low-fat eating pattern does not result in weight gain in postmenopausal women. Clinical Trial Registration ClinicalTrials.gov, NCT00000611.

    View details for Web of Science ID 000234381100019

    View details for PubMedID 16391215

  • Estrogens and progestins: background and history, trends in use, and guidelines and regimens approved by the US Food and Drug Administration. American journal of medicine Stefanick, M. L. 2005; 118: 64-73

    Abstract

    The US Food and Drug Administration (FDA) approved marketing of diethylstilbestrol in 1941 and conjugated equine estrogens (CEE) in 1942 for treatment of menopausal symptoms. Estrogen sales doubled and tripled in the mid-1960s to mid-1970s, until 1975, when reports of increased endometrial cancer in estrogen users resulted in a dramatic decline. Estrogen use increased again, with evidence of protective effects of progestins on estrogen-induced endometrial changes, combined with a 1982 report that Premarin (conjugated estrogen tablets; Wyeth Pharmaceuticals, Philadelphia, PA) retained bone mass and a 1984 National Institutes of Health (NIH) Consensus Conference on Osteoporosis statement that estrogens were the most effective means for preventing bone loss. Despite conflicting reports in 1985 regarding the relation between estrogens and coronary heart disease (CHD), many published observations of reduced CHD risk in estrogen users--reinforced by clinical trial findings in 1995 of favorable lipoprotein changes in women assigned to CEE with or without a progestin--promoted increased use through the 1990s. By 2001, approximately 15 million US women were using estrogen therapy, with or without progestins. The 2002 Women's Health Initiative (WHI) report of greater harm than benefit of combined CEE plus a progestin resulted in a precipitous decrease in estrogen and progestin use and a serious reevaluation of menopausal hormone therapy, as well as increased interest in alternative approaches to managing menopausal symptoms, including use of "bioidentical" hormones. FDA guidelines regarding treatment indications for vasomotor symptoms, vaginal atrophy, and osteoporosis prevention have resulted in approval of several estrogen (and progestin) formulations, doses, and routes of administration, thereby providing many options for women who seek conventional therapy.

    View details for PubMedID 16414329

  • Design and baseline characteristics of the osteoporotic fractures in men (MrOS) study - A large observational study of the determinants of fracture in older men CONTEMPORARY CLINICAL TRIALS Orwoll, E., Blank, J. B., Barrett-Connor, E., Cauley, J., Cummings, S., Ensrud, K., Lewis, C., Cawthon, P. M., Marcus, R., Marshall, L. M., McGowan, J., Phipps, K., Sherman, S., Stefanick, M. L., Stone, K. 2005; 26 (5): 569-585

    Abstract

    Very little information is available to direct the prevention or management of osteoporosis in men. The Osteoporotic Fractures in Men (MrOS) Study is a prospective cohort study designed to examine the extent to which fracture risk is related to bone mass, bone geometry, lifestyle, anthropometric and neuromuscular measures, and fall propensity, as well as to determine how fractures affect quality of life in men. The study is also designed to understand how osteoporosis is related to prostate disease. At baseline, participants completed questionnaires regarding medical history, medications, physical activity, diet, alcohol intake, and cigarette smoking. Objective measures of anthropometric, neuromuscular, vision, strength, and cognitive variables were obtained. Skeletal assessments included DEXA, calcaneal ultrasound, and vertebral radiographs. Vertebral and proximal femoral QCT was performed on a subset (65%). Serum, urine, and DNA specimens were collected. After the baseline assessments, a questionnaire is mailed to participants every 4 months to ascertain incident falls, fractures, prostate cancer, and deaths. After an average of 4.5 years, participants are scheduled to return for a second comprehensive visit. Men were eligible if > or =65 years. 5995 men enrolled with a mean (+/-SD) age of 73.7 (+/-5.9) years, 11% of which were minorities. Most rated their health as good/excellent. Few were current smokers, although 59% had smoked previously, and 35% reported no alcohol intake, while 47% consumed at least 2 drinks per week. The mean (range) body mass index was 26.9 kg/m2 (17-56). A non-traumatic fracture after age 50 was reported by 17% of the cohort. The MrOS cohort should provide valuable information concerning the determinants of fracture in men and should help set the stage for the development of effective methods to identify those at risk.

    View details for DOI 10.1016/j.cct.2005.05.006

    View details for Web of Science ID 000232023400007

    View details for PubMedID 16084776

  • Postmenopausal hormone therapy and body composition - a substudy of the estrogen plus progestin trial of the Women's Health Initiative AMERICAN JOURNAL OF CLINICAL NUTRITION Chen, Z., Bassford, T., Green, S. B., Cauley, J. A., Jackson, R. D., LaCroix, A. Z., LeBoff, M., Stefanick, M. L., Margolis, K. L. 2005; 82 (3): 651-656

    Abstract

    It has been suggested that hormone therapy may help counter undesirable changes in body composition in older women.This study was designed to test whether estrogen plus progestin (E+P) therapy favorably affects age-related changes in body composition in postmenopausal women.The substudy was composed of 835 women from the estrogen plus progestin trial of the Women's Health Initiative who were randomly assigned to receive either E+P therapy (n = 437) or placebo (n = 398). The women had a mean age of 63.1 y and, on average, were 13.8 y past menopause. More than 17% of the participants were from an ethnic minority. No significant differences in baseline body composition (measured with dual-energy X-ray absorptiometry) by intervention assignment were observed.After 3 y of intervention, the women who received active E+P therapy lost less lean soft tissue mass (-0.04 kg) than did the women who received placebo (-0.44 kg; P = 0.001). Additionally, the women in the E+P group had less upper-body fat distribution than did the women in the placebo group (change in ratio of trunk to leg fat mass: -0.025 for the E+P group and 0.004 for the placebo group; P = 0.003). A sensitivity analysis, which was conducted on the women who took > or = 80% of the study medication during the intervention period, corroborated the findings from the intent-to-treat analysis.A 3-y E+P intervention significantly reduced both the loss of lean soft tissue mass and the ratio of trunk to leg fat mass in postmenopausal women. However, the effect sizes were small, and whether these changes in body composition lead to significant health benefits remains to be confirmed.

    View details for Web of Science ID 000231809900024

    View details for PubMedID 16155280

  • Combined postmenopausal hormone therapy and cardiovascular disease: Toward resolving the discrepancy between observational studies and the women's health initiative clinical trial AMERICAN JOURNAL OF EPIDEMIOLOGY Prentice, R. L., Langer, R., Stefanick, M. L., Howard, B. V., Pettinger, M., Anderson, G., Barad, D., Curb, J. D., Kotchen, J., Kuller, L., Limacher, M., Wactawski-Wende, J. 2005; 162 (5): 404-414

    Abstract

    Observational research on postmenopausal hormone therapy suggests a 40-50% reduction in coronary heart disease incidence among women using these preparations. In contrast, the Women's Health Initiative clinical trial of estrogen plus progestin found an elevated incidence over a 5.6-year intervention period through July 7, 2002. Toward explaining this discrepancy, the authors analyzed data from this trial, which included 16,608 postmenopausal women aged 50-79 years, and corresponding data from 53,054 women in the Women's Health Initiative observational study, 33% of whom were estrogen-plus-progestin users at baseline. Estrogen-plus-progestin hazard ratio estimates for coronary heart disease, stroke, and venous thromboembolism in the observational study were 39-48% lower than those in the clinical trial following age adjustment. However, hazard ratios tended to decrease with increasing time from initiation of estrogen-plus-progestin use, and observational study hazard ratio estimates are heavily weighted by longer-term use while clinical trial hazard ratio estimates reflect shorter-term use. Following control for time from estrogen-plus-progestin initiation and confounding, hazard ratio estimates were rather similar for the two cohorts, although there was evidence of some remaining difference for stroke. These analyses have implications for both the design and the analysis of observational studies.

    View details for DOI 10.1093/aje/kwi223

    View details for Web of Science ID 000231363800002

    View details for PubMedID 16033876

  • Voluntary weight reduction in older men increases hip bone loss: The Osteoporotic Fractures in Men study JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Ensrud, K. E., Fullman, R. L., Barrett-Connor, E., Cauley, J. A., Stefanick, M. L., Fink, H. A., Lewis, C. E., Orwoll, E. 2005; 90 (4): 1998-2004

    Abstract

    To test the hypothesis that weight loss in older men is associated with increased rates of hip bone loss regardless of adiposity and intention to lose weight, we measured body weight, body composition, hip bone mineral density (BMD), and intention to lose weight in a cohort of 1342 older men enrolled in the Osteoporotic Fractures in Men (MrOS) study and followed them prospectively for an average of 1.8 yr for changes in weight and BMD. The adjusted average rate of change in total hip BMD was 0.1%/yr in men with weight gain, -0.3%/yr in men with stable weight, and -1.4%/yr in men with weight loss (test for trend, P < 0.001). Higher rates of hip bone loss were observed in men with weight loss regardless of category of body mass index, body composition, or intention to lose weight. Even among obese (body mass index, > or =30 kg/m2) men trying to lose weight, those with documented voluntary weight reduction experienced an increase in hip bone loss (average rate of change in total hip BMD, 0.5%/yr in those with weight gain, -0.1%/yr in those with stable weight, and -1.7%/yr in those with weight loss; test for trend, P < 0.001). Older men who experience weight loss have increased rates of hip bone loss, even among overweight and obese men undergoing voluntary weight reduction.

    View details for DOI 10.1210/jc.2004-1805

    View details for Web of Science ID 000228198900014

    View details for PubMedID 15671096

  • Risk of cardiovascular disease by hysterectomy status, with and without oophorectomy - The Women's Health Initiative Observational Study CIRCULATION Howard, B. V., Kuller, L., Langer, R., Manson, J. E., Allen, C., Assaf, A., Cochrane, B. B., Larson, J. C., Lasser, N., Rainford, M., Van Horn, L., Stefanick, M. L., Trevisan, M. 2005; 111 (12): 1462-1470

    Abstract

    Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in women and may vary by hysterectomy (or oophorectomy) status. This study compared CVD risk factors and rates between postmenopausal women who had and had not undergone hysterectomy, with or without oophorectomy.This analysis was conducted on 89 914 women in the Women's Health Initiative (WHI) Observational Study. Participants reported demographic characteristics, medical history, dietary habits, physical activity, medications, and previous hysterectomy (with or without oophorectomy). Baseline weight, height, waist circumference, and blood pressure were measured. CVD events were ascertained during 5.1 years of mean follow-up and adjudicated with standard criteria. Black, Hispanic, and American Indian women had higher rates of hysterectomy than white women (52.9%, 44.6%, and 49.2% versus 40.0%, respectively), and Asian/Pacific Islander women had lower rates (33.8%). Women with a hysterectomy (regardless of oophorectomy status) had an adverse risk profile at baseline compared with women with no hysterectomy, including a higher proportion of hypertension, diabetes, high cholesterol, obesity, and lower education, income, and physical activity (all P<0.01). Total mortality and fatal and nonfatal CVD were higher among women with a hysterectomy. Hysterectomy (regardless of oophorectomy status) was a significant predictor of CVD (HR: 1.26, P<0.001). After adjustment for demographic variables and CVD risk factors, the effect was reduced and nonsignificant.Women with a hysterectomy had a worse risk profile and higher prevalence and incidence of CVD in this cohort. Multivariate models suggest that hysterectomy is not the major determinant of this outcome; rather, CVD risk may be due to the more adverse initial risk profile of women who had undergone hysterectomy.

    View details for DOI 10.1161/01.CIR.0000159344.21672.FD

    View details for Web of Science ID 000227984800003

    View details for PubMedID 15781742

  • Association between reported alcohol intake and cognition: Results from the Women's Health Initiative Memory Study AMERICAN JOURNAL OF EPIDEMIOLOGY Espeland, M. A., Gu, L., Masaki, K. H., Langer, R. D., Coker, L. H., Stefanick, M. L., Ockene, J., Rapp, S. R. 2005; 161 (3): 228-238

    Abstract

    Some, but not all, observational studies have suggested that moderate levels of alcohol intake may be associated with improved cognitive function and reduced risk of cognitive decline and dementia. The authors of this 1996-2002 study used data from the Women's Health Initiative Memory Study of postmenopausal combination hormone therapy to assess cross-sectional and prospective associations of self-reported alcohol intake with cognitive function. Across 39 US academic medical centers, 4,461 community-dwelling women aged 65-79 years were followed an average of 4.2 years with annual Modified Mini-Mental State Examinations and standardized protocols for detecting mild cognitive impairment and probable dementia. Compared with no intake, intake of > or =1 drink per day was associated with higher baseline Modified Mini-Mental State Examination scores (p < 0.001) and a covariate-adjusted odds ratio of 0.40 (95% confidence interval: 0.28, 0.99) for significant declines in cognitive function. Associations with incident probable dementia and mild cognitive impairment were of similar magnitude but were not statistically significant after covariate adjustment. Associations with intakes of <1 drink per day were intermediate. Moderate levels of alcohol intake may be associated with better cognition and reduced risk of significant cognitive decline; however, confounding associations with unmeasured factors cannot be ruled out.

    View details for DOI 10.1093/aje/kwi043

    View details for Web of Science ID 000226604900004

    View details for PubMedID 15671255

  • The rise and fall of menopausal hormone therapy ANNUAL REVIEW OF PUBLIC HEALTH Barrett-Connor, E., Grady, D., Stefanick, M. L. 2005; 26: 115-140

    Abstract

    Clinical trials show that hormone therapy (HT) is an effective treatment for vasomotor symptoms and vaginal dryness. HT improves other symptoms including sleep and quality of life in women who have menopause symptoms. In the Women's Health Initiative controlled clinical trials, both estrogen therapy (ET) and estrogen plus progestin therapy (EPT) reduced fracture risk, neither reduced the risk of heart disease, and both increased the risk of stroke, deep vein thrombosis, and dementia. EPT, but not ET, increased breast cancer risk and reduced colon cancer risk. Differences between EPT and ET may reflect chance, baseline differences between the EPT and ET cohorts, or a progestin effect. Studies of younger women and lower HT doses with intermediate endpoints are beginning.

    View details for DOI 10.1146/annurev.publhealth.26.021304.144637

    View details for Web of Science ID 000228981500006

    View details for PubMedID 15760283

  • Insulin, physical activity, and caloric intake in postmenopausal women: Breast cancer implications JOURNAL OF CLINICAL ONCOLOGY Chlebowski, R. T., Pettinger, M., Stefanick, M. L., Howard, B. V., Mossavar-Rahmani, Y., McTiernan, A. 2004; 22 (22): 4507-4513

    Abstract

    Increased physical activity and programs to reduce body mass index (BMI) with both increased physical activity and decreased caloric intake have been proposed to reduce insulin as a potential mediator of breast cancer and other chronic diseases. However, there are few data on the relative contribution of physical activity, caloric intake, and BMI to fasting insulin levels.An ethnically diverse subsample of 2,996 mostly healthy postmenopausal women with no prior cancer history was randomly identified from the 161,809 participants in the Women's Health Initiative clinical trials and observational study. Information was collected on diet, recreational physical activity, and anthropometrics including BMI. Fasting insulin levels were determined. Using a cross-sectional design, insulin levels were then compared across quintiles of caloric intake and physical activity in linear regression model analyses controlled for BMI and other factors.Lower BMI (P < .0001), higher levels of physical activity (P < .0001), and lower caloric intake (P < .02) were all independently associated with significantly lower mean fasting insulin levels throughout the range of observed values. Insulin levels of 8.74 microU/mL +/- 4.16 SD were seen in the highest physical activity and lowest caloric intake quintile compared with insulin levels of 15.08 microU/mL +/- 16.32 SD in the lowest physical activity and highest caloric intake quintile (P < .0001).These findings suggest that reduction in BMI achieved by increasing physical activity, reducing caloric intake, or both, should lower insulin levels, providing support for clinical trials evaluating insulin level change and breast cancer risk.

    View details for DOI 10.1200/JCO.2004.04.119

    View details for Web of Science ID 000225175600012

    View details for PubMedID 15542801

  • On the importance of using multiple methods of dietary assessment EPIDEMIOLOGY Natarajan, L., Rock, C. L., Major, J. M., Thomson, C. A., Caan, B. J., Flatt, S. W., Chilton, J. A., Hollenbach, K. A., Newman, V. A., Faerber, S., Ritenbaugh, C. K., Gold, E., Stefanick, M. L., Jones, L. A., Marshall, J. R., Pierce, J. P. 2004; 15 (6): 738-745

    Abstract

    Plasma carotenoid concentrations reflect intake of vegetables and fruits, the major food sources of these compounds. This study compared the ability of 2 measures of dietary intake (24-hour diet recalls and food frequency questionnaires [FFQs]) to corroborate plasma carotenoid concentrations in a subset of women participating in a diet intervention trial.Plasma carotenoid concentrations and dietary intakes, estimated from 24-hour diet recalls and FFQs, were examined at baseline and 1 year later in a subset of 395 study participants (197 intervention and 198 comparison group). We used longitudinal models to examine associations between estimated intakes and plasma carotenoid concentrations. These analyses were stratified by study group and adjusted for body mass index (BMI), plasma cholesterol concentration, and total energy intake. We conducted simulations to compare mean-squared errors of prediction of each assessment method.In mixed-effects models, the estimated carotenoid intakes from both dietary assessment methods were strongly associated with plasma concentrations of alpha-carotene, beta-carotene, and lutein. Furthermore, modeling the 2 sources of intake information as joint predictors reduced the prediction error.These findings underscore the importance of using multiple measures of dietary assessment in studies examining diet-disease associations.

    View details for DOI 10.1097/01.ede.0000135178.36362.ef

    View details for Web of Science ID 000224697200013

    View details for PubMedID 15475724

  • Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women - Women's Health Initiative Memory Study JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Shumaker, S. A., Legault, C., Kuller, L., Rapp, S. R., Thal, L., Lane, D. S., Fillit, H., Stefanick, M. L., Hendrix, S. L., Lewis, C. E., Masaki, K., Coker, L. H. 2004; 291 (24): 2947-2958

    Abstract

    The Women's Health Initiative Memory Study (WHIMS) previously found increased risk for dementia and no effect on mild cognitive impairment (MCI) in women treated with conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA).To determine the effects of CEE alone and CEE plus MPA on incidence of probable dementia and MCI in older women.Randomized, double-blind, placebo-controlled clinical trials of CEE (estrogen-alone trial) or CEE plus MPA (estrogen plus progestin trial) in community-dwelling women aged 65 to 79 years, conducted from June 1995 to July 8, 2002 (estrogen plus progestin; n = 4532), or to February 29, 2004 (estrogen-alone; n = 2947), in 39 of the 40 WHI clinical centers.In the estrogen-alone trial, 1 daily tablet containing either 0.625 mg/d of CEE vs matching placebo; in the estrogen plus progestin trial, 1 daily tablet containing CEE (0.625 mg/d) plus MPA (2.5 mg/d) vs matching placebos.Probable dementia and MCI.In the estrogen-alone trial, 47 participants were diagnosed with probable dementia, of whom 28 were assigned to CEE and 19 to placebo (hazard ratio [HR], 1.49; 95% confidence interval [CI], 0.83-2.66). Incidence rates for probable dementia in the estrogen-alone trial were statistically similar to those in the estrogen plus progestin trial (45 vs 22 per 10 000 person-years for CEE plus MPA vs placebo, respectively; P =.11). When data were pooled per the original WHIMS protocol, the overall HR for probable dementia was 1.76 (95% CI, 1.19-2.60; P =.005). After excluding participants with baseline Modified Mini-Mental State Examination scores at or below the screening cut point, the HR was 1.77 (95% CI, 0.74-4.23; P =.20) in the estrogen-alone trial and 2.19 (95% CI, 1.25-3.84; P =.006) in the pooled trials. In the estrogen-alone trial, 76 participants were diagnosed with MCI in the CEE group vs 58 in the placebo group (HR, 1.34; 95% CI, 0.95-1.89). In the combined trial data, the HR was similar (1.25; 95% CI, 0.97-1.60). In the estrogen-alone trial, 93 participants receiving CEE were diagnosed with either probable dementia or MCI vs 69 receiving placebo (HR, 1.38; 95% CI, 1.01-1.89; P =.04).Estrogen therapy alone did not reduce dementia or MCI incidence and increased the risk for both end points combined. Pooling data for estrogen alone and estrogen plus progestin resulted in increased risks for both end points. Use of hormone therapy to prevent dementia or cognitive decline in women 65 years of age or older is not recommended.

    View details for Web of Science ID 000222184600024

    View details for PubMedID 15213206

  • Effects of a high-fiber, low-fat diet intervention on serum concentrations of reproductive steroid hormones in women with a history of breast cancer JOURNAL OF CLINICAL ONCOLOGY Rock, C. L., Flatt, S. W., Thomson, C. A., Stefanick, M. L., Newman, V. A., Jones, L. A., Natarajan, L., Ritenbaugh, C., Hollenbach, K. A., Pierce, J. P., Chang, R. J. 2004; 22 (12): 2379-2387

    Abstract

    Diet intervention trials are testing whether postdiagnosis dietary modification can influence breast cancer recurrence and survival. One possible mechanism is an effect on reproductive steroid hormones. Participants andSerum reproductive steroid hormones were measured at enrollment and 1 year in 291 women with a history of breast cancer who were enrolled onto a randomized, controlled diet intervention trial. Dietary goals for the intervention group were increased fiber, vegetable, and fruit intakes and reduced fat intake. Estradiol, bioavailable estradiol, estrone, estrone sulfate, androstenedione, testosterone, dehydroepiandrosterone sulfate, follicle-stimulating hormone, and sex hormone-binding globulin were measured.The intervention (but not the comparison) group reported a significantly lower intake of energy from fat (21% v 28%), and higher intake of fiber (29 g/d v 22 g/d), at 1-year follow-up (P <.001). Significant weight loss did not occur in either group. A significant difference in the change in bioavailable estradiol concentration from baseline to 1 year in the intervention (-13 pmol/L) versus the comparison (+3 pmol/L) group was observed (P <.05). Change in fiber (but not fat) intake was significantly and independently related to change in serum bioavailable estradiol (P <.01) and total estradiol (P <.05) concentrations.Results from this study indicate that a high-fiber, low-fat diet intervention is associated with reduced serum bioavailable estradiol concentration in women diagnosed with breast cancer, the majority of whom did not exhibit weight loss. Increased fiber intake was independently related to the reduction in serum estradiol concentration.

    View details for DOI 10.1200/JCO.2004.09.025

    View details for Web of Science ID 000222153400016

    View details for PubMedID 15197199

  • Effects of conjugated, equine estrogen in postmenopausal women with hysterectomy - The women's health initiative randomized controlled trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Anderson, G. L., Limacher, M., Assaf, A. R., Bassford, T., Beresford, S. A., BLACK, H., Bonds, D., Brunner, R., Brzyski, R., Caan, B., Chlebowski, R., Curb, D., Gass, M., Hays, J., Heiss, G., Hendrix, S., Howard, B. V., Hsia, J., Hubbell, A., Jackson, R., Johnson, K. C., Judd, H., Kotchen, J. M., Kuller, L., LaCroix, A. Z., Lane, D., Langer, R. D., Lasser, N., Lewis, C. E., Manson, J., Margolis, K., Ockene, J., O'Sullivan, M. J., Phillips, L., Prentice, R. L., Ritenbaugh, C., Robbins, J., Rossouw, J. E., Sarto, G., Stefanick, M. L., Van Horn, L., Wactawski-Wende, J., Wallace, R., Wassertheil-Smoller, S. 2004; 291 (14): 1701-1712

    Abstract

    Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain.To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States.A randomized, double-blind, placebo-controlled disease prevention trial (the estrogen-alone component of the Women's Health Initiative [WHI]) conducted in 40 US clinical centers beginning in 1993. Enrolled were 10 739 postmenopausal women, aged 50-79 years, with prior hysterectomy, including 23% of minority race/ethnicity.Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo.The primary outcome was coronary heart disease (CHD) incidence (nonfatal myocardial infarction or CHD death). Invasive breast cancer incidence was the primary safety outcome. A global index of risks and benefits, including these primary outcomes plus stroke, pulmonary embolism (PE), colorectal cancer, hip fracture, and deaths from other causes, was used for summarizing overall effects.In February 2004, after reviewing data through November 30, 2003, the National Institutes of Health (NIH) decided to end the intervention phase of the trial early. Estimated hazard ratios (HRs) (95% confidence intervals [CIs]) for CEE vs placebo for the major clinical outcomes available through February 29, 2004 (average follow-up 6.8 years), were: CHD, 0.91 (0.75-1.12) with 376 cases; breast cancer, 0.77 (0.59-1.01) with 218 cases; stroke, 1.39 (1.10-1.77) with 276 cases; PE, 1.34 (0.87-2.06) with 85 cases; colorectal cancer, 1.08 (0.75-1.55) with 119 cases; and hip fracture, 0.61 (0.41-0.91) with 102 cases. Corresponding results for composite outcomes were: total cardiovascular disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures, 0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22), and the global index, 1.01 (0.91-1.12). For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years.The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.

    View details for Web of Science ID 000220788700027

    View details for PubMedID 15082697

  • Estrogen plus progestin and colorectal cancer in postmenopausal women NEW ENGLAND JOURNAL OF MEDICINE Chlebowski, R. T., Wactawski-Wende, J., Ritenbaugh, C., Hubbell, F. A., Ascensao, J., Rodabough, R. J., Rosenberg, C. A., Taylor, V. M., Harris, R., Chen, C., Adams-Campbell, L. L., White, E., Alving, B., Rossouw, J., Pottern, L., Ludlam, S., McGowan, J., Prentice, R., Anderson, G., Lacroix, A., Patterson, R., McTiernan, A., Cochrane, B., Hunt, J., Tinker, L., Kooperberg, C., McIntosh, M., Wang, C. Y., Chen, C., Bowen, D., Kristal, A., Stanford, J., Urban, N., Weiss, N., White, E., Shumaker, S., Rautaharju, P., Prineas, R., Naughton, M., Stein, E., Laskarzewski, P., Cummings, S., Nevitt, M., Dockrell, M., Harnack, L., Cammarata, F., Lindenfelser, S., Psaty, B., Heckbert, S., Wassertheil-Smoller, S., Frishman, W., Wylie-Rosett, J., Barad, D., Freeman, R., Hays, J., Young, R., Anderson, J., Lithgow, S., Bray, P., Manson, J., Buring, J., Gaziano, J. M., Rexrode, K., Chae, C., Assaf, A. R., WHEELER, C., Eaton, C., Cyr, M., Phillips, L., PEDERSEN, M., Strickland, O., Huber, M., Porter, V., Beresford, S. A., Taylor, V. M., Woods, N. F., Henderson, M., Kestin, M., Hsia, J., Gaba, N., Ascensao, J., Chlebowski, R., Detrano, R., Nelson, A., Heiner, J., Marshall, J., Ritenbaugh, C., Valanis, B., Elmer, P., Stevens, V., Karanja, N., Caan, B., Sidney, S., Bailey, G., HIRATA, J., Kotchen, J. M., Barnabei, V., Kotchen, T. A., Gilligan, M. A., Neuner, J., Howard, B. V., Adams-Campbell, L., Passaro, M., Rainford, M., Agurs-Collins, T., Van Horn, L., Greenland, P., Khandekar, J., Liu, K., Rosenberg, C., BLACK, H., Powell, L., Mason, E., Stefanick, M. L., Hlatky, M. A., Chen, B., Stafford, R. S., Giudice, L. C., Lane, D., Granek, I., Lawson, W., San Roman, G., Messina, C., Jackson, R., Harris, R., Paskett, E., Mysiw, W. J., Blumenfeld, M., Lewis, C. E., Oberman, A., Shikany, J. M., Safford, M., Britt, B. K., Bassford, T., Mattox, J., Ko, M., Lohman, T., Wactawski-Wende, J., Trevisan, M., Smit, E., Graham, S., Chang, J., Robbins, J., Yasmeen, S., Lindfors, K., Stern, J., Hubbell, A., Frank, G., Wong, N., Greep, N., Monk, B., Judd, H., Heber, D., Elashoff, R., Langer, R. D., Criqui, M. H., Talavera, G. T., Garland, C. F., Hanson, R. E., Gass, M., Wernke, S., Watts, N., Limacher, M., Perri, M., Kaunitz, A., Williams, R. S., Brinson, Y., Curb, D., Petrovitch, H., Rodriguez, B., Masaki, K., Sharma, S., Wallace, R., Torner, J., JOHNSON, S., Snetselaar, L., VanVoorhis, B., Ockene, J., Rosal, M., Ockene, I., Yood, R., Aronson, P., Lasser, N., Singh, B., Lasser, V., Kostis, J., O'Sullivan, M. J., PARKER, L., Estape, R., Fernandez, D., Margolis, K. L., Grimm, R. H., Hunninghake, D. B., LaValleur, J., Kempainen, S., Brunner, R., Graettinger, W., Oujevolk, V., Heiss, G., Haines, P., Ontjes, D., Sueta, C., Wells, E., Kuller, L., Cauley, J., Milas, N. C., Johnson, K. C., Satterfield, S., Ke, R. W., Vile, J., Tylavsky, F., Brzyski, R., Schenken, R., Trabal, J., Rodriguez-Sifuentes, M., Mouton, C., Sarto, G., Laube, D., McBride, P., Mares-Perlman, J., Loevinger, B., Bonds, D., BURKE, G., Crouse, R., Parsons, L., Vitolins, M., Hendrix, S., Simon, M., McNeely, G., Gordon, P., MAKELA, P., Allen, C., Dougherty, S., Carleton, R. 2004; 350 (10): 991-1004

    Abstract

    Although the Women's Health Initiative (WHI) trial of estrogen plus progestin in postmenopausal women identified more overall health risks than benefits among women in the hormone group, the use of estrogen plus progestin was associated with a significant decrease in the risk of colorectal cancer. We analyzed features of the colorectal cancers that developed and their relation to the characteristics of the participants.In the WHI trial, 16,608 postmenopausal women who were 50 to 79 years of age and had an intact uterus were randomly assigned to a combination of conjugated equine estrogens (0.625 mg per day) plus medroxyprogesterone acetate (2.5 mg per day) or placebo. The main outcome measures were the incidence, stages, and types of colorectal cancer, as determined by blinded central adjudication.There were 43 invasive colorectal cancers in the hormone group and 72 in the placebo group (hazard ratio, 0.56; 95 percent confidence interval, 0.38 to 0.81; P=0.003). The invasive colorectal cancers in the hormone group were similar in histologic features and grade to those in the placebo group but with a greater number of positive lymph nodes (mean +/-SD, 3.2+/-4.1 vs. 0.8+/-1.7; P=0.002) and were more advanced (regional or metastatic disease, 76.2 percent vs. 48.5 percent; P=0.004). In exploratory analyses, women in the hormone group with antecedent vaginal bleeding had colorectal cancers with a greater number of positive nodes than women in the hormone group who did not have vaginal bleeding (3.8+/-4.3 vs. 0.7+/-1.5 nodes, P=0.006).Relatively short-term use of estrogen plus progestin was associated with a decreased risk of colorectal cancer. However, colorectal cancers in women who took estrogen plus progestin were diagnosed at a more advanced stage than those in women who took placebo.

    View details for Web of Science ID 000189363600007

    View details for PubMedID 14999111

  • Women's Ischemic Syndrome Evaluation - Current status and future research directions - Report of the National Heart, Lung and Blood Institute Workshop - October 2-4, 2002 - Section 4 - Lessons from hormone replacement trials CIRCULATION Waters, D. D., GORDON, D., Rossouw, J. E., Cannon, R. O., Collins, P., Herrington, D. M., Hsia, J., Langer, R., Mosca, L., Ouyang, P., Sopko, G., Stefanick, M. L. 2004; 109 (6): E53-E55
  • Telephone counseling intervention increases intakes of micronutrient- and phytochemical-rich vegetables, fruit and fiber in breast cancer survivors JOURNAL OF NUTRITION Pierce, J. P., Newman, V. A., Flatt, S. W., Faerber, S., Rock, C. L., Natarajan, L., Caan, B. J., Gold, E. B., Hollenbach, K. A., Wasserman, L., Jones, L., Ritenbaugh, C., Stefanick, M. L., Thomson, C. A., Kealey, S. 2004; 134 (2): 452-458

    Abstract

    Although a large body of evidence suggests that diet may play an important role in cancer prevention, randomized controlled trials reported to date have not achieved sufficient increases in protective micronutrients and phytochemicals to adequately test the hypothesis that diet can reduce cancer risk. The Women's Healthy Eating and Living (WHEL) Study, a randomized controlled trial of the role diet modification may play in future breast cancer events, introduced an innovative theory-based telephone counseling intervention to teach participants to consume a high fiber, low fat diet emphasizing vegetables and fruits rich in carotenoids and other potentially protective phytochemicals. This report examines the baseline to 12-mo changes in dietary intakes of 2970 participants, assessed through 24-h recalls and validated with plasma carotenoid concentrations. At 12 mo, the intervention group reported a significantly increased daily vegetable intake (+vegetable juice) of 7.1 servings (+82%) and fruit intake of 3.9 servings (+18%). Fiber intake increased from 3.04 to 4.16 g/(MJ. d), whereas energy from fat decreased significantly from 28.6 to 23.7%. Plasma carotenoid concentrations increased significantly, i.e., alpha-carotene (+223%); beta-carotene (+87%); lutein (+29%); and lycopene (+17%). In the comparison group, dietary intake and plasma carotenoid concentrations were essentially identical to those of the intervention group at baseline and were unchanged at 12 mo. The WHEL Study showed that a telephone counseling intervention can achieve major increases in micronutrient- and phytochemical-rich vegetables, fruit and fiber intakes, enabling an investigation of the potential cancer preventive effects of these food components.

    View details for Web of Science ID 000188708100026

    View details for PubMedID 14747688

  • Plasma triacylglycerol and HDL cholesterol concentrations confirm self-reported changes in carbohydrate and fat intakes in women in a diet intervention trial JOURNAL OF NUTRITION Rock, C. L., Flatt, S. W., Thomson, C. A., Stefanick, M. L., Newman, V. A., Jones, L., Natarajan, L., Pierce, J. P., Chang, R. J., WITZTUM, J. L. 2004; 134 (2): 342-347

    Abstract

    Diet intervention trials are currently testing whether reduced fat intake can reduce the risk and progression of breast cancer. Energy from dietary fat is generally replaced by energy from carbohydrate in these studies, and altering the proportion of energy from dietary carbohydrate and fat has been shown to affect plasma lipid concentrations in controlled feeding studies. The purpose of this study was to examine the effect of increased carbohydrate and reduced fat intakes on plasma lipids in a randomized, controlled trial that is testing the effect of diet modification on risk for recurrence and survival in women previously treated for breast cancer. Plasma concentrations of lipids and related factors were measured at enrollment and 1-y follow-up in 393 women enrolled in the trial. Dietary goals for the intervention group focused on an increase in vegetable, fruit and fiber intakes, and reduced fat intake. Women assigned to the intervention group significantly reduced fat intake (from 28.1 to 21.0% of energy), and significantly increased intakes of carbohydrate (from 56.9 to 65.3% of energy) and fiber (from 21.0 to 29.6 g/d) (P < 0.05). Body weight did not change significantly in either study group. A small but significant increase in fasting plasma triacylglycerol concentration, and decreases in HDL cholesterol and apoprotein-A1 concentrations, were observed in the intervention group (P < 0.05) but not in the comparison group. Changes in total cholesterol, LDL cholesterol, apoprotein-B, lipoprotein (a), and insulin concentrations, and in the LDL cholesterol/HDL cholesterol ratio, were not observed in either group. The lipid responses that were observed in this study provide biological evidence that validates the self-reported change in dietary intakes of fat and carbohydrate in response to the intervention efforts. The degree of change in these lipid concentrations was small and does not suggest increased cardiovascular disease risk.

    View details for Web of Science ID 000188708100008

    View details for PubMedID 14747670

  • National use of postmenopausal hormone therapy - Annual trends and response to recent evidence JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Hersh, A. L., Stefanick, M. L., Stafford, R. S. 2004; 291 (1): 47-53

    Abstract

    Postmenopausal hormone therapy use increased dramatically during the past 2 decades because of a prevailing belief in its health benefits. Recent evidence from randomized trials published in July 2002 demonstrated adverse cardiovascular disease events and other risks with hormone therapy in the form of oral estrogen combined with progestin.To describe patterns of hormone therapy use from 1995 until July 2003, including the impact of recent evidence.Two databases were used to describe national trends in hormone therapy use from January 1995 to July 2003. The National Prescription Audit database provided data on the number of hormone therapy prescriptions filled by retail pharmacies and the National Disease and Therapeutic Index database provided data on patient visits to office-based physicians during which hormone therapy was prescribed.Annual number of hormone therapy prescriptions and characteristics of visits to physicians during which hormone therapy was prescribed.Annual hormone therapy prescriptions increased from 58 million in 1995 to 90 million in 1999, representing approximately 15 million women per year, then remained stable through June 2002. Adoption of new oral estrogen/progestin combinations, primarily Prempro, accounted for most of this growth. Obstetrician/gynecologists provided more than 70% of hormone therapy prescriptions, and more than one third of patients were older than 60 years. Following the publication of trial results in July 2002, hormone therapy prescriptions declined in successive months. Relative to January-June 2002, prescriptions from January-June 2003 declined by 66% for Prempro and 33% for Premarin. Small increases were observed in vaginal formulations and in new prescriptions for low-dose Premarin. If prescription rates observed through July 2003 remain stable, a decline to 57 million prescriptions for 2003, similar to the rate in 1995, is projected.Clinical practice responded rapidly to recent evidence of harms associated with hormone therapy. Since July 2002, many patients have discontinued hormone therapy or are tapering to lower doses.

    View details for Web of Science ID 000187836000018

    View details for PubMedID 14709575

  • The Women's Health Initiative postmenopausal hormone trials: Overview and baseline characteristics of participants ANNALS OF EPIDEMIOLOGY Stefanick, M. L., Cochrane, B. B., Hsia, J., Barad, D. H., Liu, J. H., Johnson, S. R. 2003; 13 (9): S78-S86
  • Effects of estrogen plus progestin on risk of fracture and bone mineral density - The Women's Health Initiative randomized trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Cauley, J. A., Robbins, J., Chen, Z., Cummings, S. R., Jackson, R. D., LaCroix, A. Z., LeBoff, M., Lewis, C. E., McGowan, J., Neuner, J., Pettinger, M., Stefanick, M. L., Wactawski-Wende, J., Watts, N. B. 2003; 290 (13): 1729-1738

    Abstract

    In the Women's Health Initiative trial of estrogen-plus-progestin therapy, women assigned to active treatment had fewer fractures.To test the hypothesis that the relative risk reduction of estrogen plus progestin on fractures differs according to risk factors for fractures.Randomized controlled trial (September 1993-July 2002) in which 16 608 postmenopausal women aged 50 to 79 years with an intact uterus at baseline were recruited at 40 US clinical centers and followed up for an average of 5.6 years.Women were randomly assigned to receive conjugated equine estrogen, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102).All confirmed osteoporotic fracture events that occurred from enrollment to discontinuation of the trial (July 7, 2002); bone mineral density (BMD), measured in a subset of women (n = 1024) at baseline and years 1 and 3; and a global index, developed to summarize the balance of risks and benefits to test whether the risk-benefit profile differed across tertiles of fracture risk.Seven hundred thirty-three women (8.6%) in the estrogen-plus-progestin group and 896 women (11.1%) in the placebo group experienced a fracture (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.69-0.83). The effect did not differ in women stratified by age, body mass index, smoking status, history of falls, personal and family history of fracture, total calcium intake, past use of hormone therapy, BMD, or summary fracture risk score. Total hip BMD increased 3.7% after 3 years of treatment with estrogen plus progestin compared with 0.14% in the placebo group (P<.001). The HR for the global index was similar across tertiles of the fracture risk scale (lowest fracture risk tertile, HR, 1.20; 95% CI, 0.93-1.58; middle tertile, HR, 1.23; 95% CI, 1.04-1.46; highest tertile, HR, 1.03; 95% CI, 0.88-1.24) (P for interaction =.54).This study demonstrates that estrogen plus progestin increases BMD and reduces the risk of fracture in healthy postmenopausal women. The decreased risk of fracture attributed to estrogen plus progestin appeared to be present in all subgroups of women examined. When considering the effects of hormone therapy on other important disease outcomes in a global model, there was no net benefit, even in women considered to be at high risk of fracture.

    View details for Web of Science ID 000185606100022

    View details for PubMedID 14519707

  • Estrogen plus progestin and the risk of coronary heart disease NEW ENGLAND JOURNAL OF MEDICINE Manson, J. E., Hsia, J., Johnson, K. C., Rossouw, J. E., Assaf, A. R., Lasser, N. L., Trevisan, M., Black, H. R., Heckbert, S. R., Detrano, R., Strickland, O. L., Wong, N. D., Crouse, J. R., Stein, E., Cushman, M., Alving, B., Rossouw, J. E., Pottern, L., Ludlam, S., McGowan, J. A., Prentice, R., Anderson, G., Lacroix, A., Patterson, R., McTiernan, A., Cochrane, B., Hunt, J., Tinker, L., Kooperberg, C., McIntosh, M., Wang, C. Y., Chen, C., Bowen, D., Kristal, A., Stanford, J., Urban, N., Weiss, N., White, E., Shumaker, S., Rautaharju, P., Prineas, R., Naughton, M., Stein, E., Laskarzewski, P., Cummings, S., Nevitt, M., Dockrell, M., Harnack, L., Cammarata, F., Lindenfelser, S., Psaty, B., Heckbert, S., Wassertheil-Smoller, S., Frishman, W., Wylie-Rosett, J., Barad, D., Freeman, R., Hays, J., Young, R., Anderson, J., Lithgow, S., Bray, P., Manson, J., Buring, J., Gaziano, J. M., Rexrode, K., Chae, C., Assaf, A. R., Carleton, R., WHEELER, C., Eaton, C., Cyr, M., Phillips, L., PEDERSEN, M., Strickland, O., Huber, M., Porter, V., Beresford, S. A., Taylor, V. M., Woods, N. F., Henderson, M., Kestin, M., Hsia, J., Gaba, N., Ascensao, J., Laowattana, S., Chlebowski, R., Detrano, R., Nelson, A., Heiner, J., Marshall, J., Ritenbaugh, C., Valanis, B., Elmer, P., Stevens, V., Karanja, N., Caan, B., Sidney, S., Bailey, G., HIRATA, J., Kotchen, J. M., Barnabei, V., Kotchen, T. A., Gilligan, M. A., Neuner, J., Howard, B. V., Adams-Campbell, L., Passaro, M., Rainford, M., Agurs-Collins, T., Van Horn, L., Greenland, P., Khandekar, J., Liu, K., Rosenberg, C., BLACK, H., Powell, L., Mason, E., Stefanick, M. L., Hlatky, M. A., Chen, B., Stafford, R. S., Giudice, L. C., Lane, D., Granek, I., Lawson, W., San Roman, G., Messina, C., Jackson, R., Harris, R., Frid, D., Mysiw, W. J., Blumenfeld, M., Lewis, C. E., Oberman, A., Fouad, M. N., Shikany, J. M., West, D. S., Bassford, T., Mattox, J., Ko, M., Lohman, T., Trevisan, M., Wactawski-Wende, J., Graham, S., Chang, J., Smit, E., Robbins, J., Yasmeen, S., Lindfors, K., Stern, J., Hubbell, A., Frank, G., Wong, N., Greep, N., MoOnk, B., Judd, H., Heber, D., Elashoff, R., Langer, R. D., Criqui, M. H., Talavera, G. T., Garland, C. F., Hanson, R. E., Gass, M., Wernke, S., Watts, N., Limacher, M., Perri, M., Kaunitz, A., Williams, R. S., Brinson, Y., Curb, D., Petrovitch, H., Rodriguez, B., Masaki, K., Sharma, S., Wallace, R., Torner, J., JOHNSON, S., Snetselaar, L., VanVoorhis, B., Ockene, I., Yood, R., Aronson, P., Lasser, N., Hymowitz, N., Lasser, V., Safford, M., Kostis, J., O'Sullivan, M. J., PARKER, L., Estape, R., Fernandez, D., Margolis, K. L., Grimm, R. H., Hunninghake, D. B., LaValleur, J., Hall, K. M., Brunner, R., St Jeor, S., Graettinger, W., Oujevolk, V., Heiss, G., Haines, P., Ontjes, D., Sueta, C., Wells, E., Kuller, L., Caggiula, A., Cauley, J., Berga, S., Milas, N. C., Johnson, K. C., Satterfield, S., Ke, T. W., Vile, J., Tylavsky, F., Brzyski, R., Schenken, R., Trabal, J., Rodriguez-Sifuentes, M., Mouton, C., Allen, C., Laube, D., McBride, P., Mares-Perlman, J., Loevinger, B., BURKE, G., Crouse, R., Parsons, L., Vitolins, M., Hendrix, S., Simon, M., McNeeley, G., Gordon, P., MAKELA, P. 2003; 349 (6): 523-534

    Abstract

    Recent randomized clinical trials have suggested that estrogen plus progestin does not confer cardiac protection and may increase the risk of coronary heart disease (CHD). In this report, we provide the final results with regard to estrogen plus progestin and CHD from the Women's Health Initiative (WHI).The WHI included a randomized primary-prevention trial of estrogen plus progestin in 16,608 postmenopausal women who were 50 to 79 years of age at base line. Participants were randomly assigned to receive conjugated equine estrogens (0.625 mg per day) plus medroxyprogesterone acetate (2.5 mg per day) or placebo. The primary efficacy outcome of the trial was CHD (nonfatal myocardial infarction or death due to CHD).After a mean follow-up of 5.2 years (planned duration, 8.5 years), the data and safety monitoring board recommended terminating the estrogen-plus-progestin trial because the overall risks exceeded the benefits. Combined hormone therapy was associated with a hazard ratio for CHD of 1.24 (nominal 95 percent confidence interval, 1.00 to 1.54; 95 percent confidence interval after adjustment for sequential monitoring, 0.97 to 1.60). The elevation in risk was most apparent at one year (hazard ratio, 1.81 [95 percent confidence interval, 1.09 to 3.01]). Although higher base-line levels of low-density lipoprotein cholesterol were associated with an excess risk of CHD among women who received hormone therapy, higher base-line levels of C-reactive protein, other biomarkers, and other clinical characteristics did not significantly modify the treatment-related risk of CHD.Estrogen plus progestin does not confer cardiac protection and may increase the risk of CHD among generally healthy postmenopausal women, especially during the first year after the initiation of hormone use. This treatment should not be prescribed for the prevention of cardiovascular disease.

    View details for Web of Science ID 000184563500003

    View details for PubMedID 12904517

  • Influence of estrogen plus progestin on breast, cancer and mammography in healthy postmenopausal women - The Women's Health Initiative Randomized trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Chlebowski, R. T., Hendrix, S. L., Langer, R. D., Stefanick, M. L., Gass, M., Lane, D., Rodabough, R. J., Gilligan, M. A., Cyr, M. G., Thomson, C. A., Khandekar, J., Petrovitch, H., McTiernan, A. 2003; 289 (24): 3243-3253

    Abstract

    The Women's Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks, including invasive breast cancer, exceeded benefits. Outstanding issues not previously addressed include characteristics of breast cancers observed among women using hormones and whether diagnosis may be influenced by hormone effects on mammography.To determine the relationship among estrogen plus progestin use, breast cancer characteristics, and mammography recommendations.Following a comprehensive breast cancer risk assessment, 16 608 postmenopausal women aged 50 to 79 years with an intact uterus were randomly assigned to receive combined conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo from 1993 to 1998 at 40 clinical centers. Screening mammography and clinical breast examinations were performed at baseline and yearly thereafter.Breast cancer number and characteristics, and frequency of abnormal mammograms by estrogen plus progestin exposure.In intent-to-treat analyses, estrogen plus progestin increased total (245 vs 185 cases; hazard ratio [HR], 1.24; weighted P<.001) and invasive (199 vs 150 cases; HR, 1.24; weighted P =.003) breast cancers compared with placebo. The invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology and grade but were larger (mean [SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively; P =.04) and were at more advanced stage (regional/metastatic 25.4% vs 16.0%, respectively; P =.04) compared with those diagnosed in the placebo group. After 1 year, the percentage of women with abnormal mammograms was substantially greater in the estrogen plus progestin group (716 [9.4%] of 7656) compared with placebo group (398 [5.4%] of 7310; P<.001), a pattern which continued for the study duration.Relatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms. These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis.

    View details for Web of Science ID 000183704600017

    View details for PubMedID 12824205

  • Effect of estrogen plus progestin on global cognitive function in postmenopausal women - The Women's Health Initiative Memory Study: A randomized controlled trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Rapp, S. R., Espeland, M. A., Shumaker, S. A., Henderson, V. W., Brunner, R. L., Manson, J. E., Gass, M. L., Stefanick, M. L., Lane, D. S., Hays, J., Johnson, K. C., Coker, L. H., Dailey, M., Bowen, D. 2003; 289 (20): 2663-2672

    Abstract

    Observational studies have suggested that postmenopausal hormone treatment may improve cognitive function, but data from randomized clinical trials have been sparse and inconclusive. The Women's Health Initiative Memory Study (WHIMS) is an ancillary study of the Women's Health Initiative (WHI) hormone therapy trials. On July 8, 2002, the estrogen plus progestin therapy in the WHI trial was discontinued because of certain increased health risks for women.To determine whether estrogen plus progestin therapy protects global cognitive function in older postmenopausal women.A randomized, double-blind, placebo-controlled clinical trial, WHIMS is an ancillary study of geographically diverse, community-dwelling women aged 65 years or older from 39 of 40 clinical centers within the WHI estrogen plus progestin trial that started in June 1995. Of 4894 eligible postmenopausal women aged 65 years or older and free of probable dementia at baseline, 4532 (92.6%) were enrolled in the estrogen plus progestin component of WHIMS. A total of 4381 participants (96.7%) provided at least 1 valid cognitive function score between June 1995 and July 8, 2002.Participants received either 1 daily tablet containing 0.625 mg of conjugated equine estrogen with 2.5 mg of medroxyprogesterone acetate (n = 2145) or matching placebo (n = 2236).Global cognitive function measured annually with the Modified Mini-Mental State Examination.The Modified Mini-Mental State Examination mean total scores in both groups increased slightly over time (mean follow-up of 4.2 years). Women in the estrogen plus progestin group had smaller average increases in total scores compared with women receiving placebo (P =.03), but these differences were not clinically important. Removing women by censoring them after adjudicated dementia, mild cognitive impairment, or stroke, and nonadherence to study protocol, did not alter the findings. Prior hormone therapy use and duration of prior use did not affect the interpretation of the results, nor did timing of prior hormone therapy initiation with respect to the final menstrual period. More women in the estrogen plus progestin group had a substantial and clinically important decline (> or =2 SDs) in Modified Mini-Mental State Examination total score (6.7%) compared with the placebo group (4.8%) (P =.008).Among postmenopausal women aged 65 years or older, estrogen plus progestin did not improve cognitive function when compared with placebo. While most women receiving estrogen plus progestin did not experience clinically relevant adverse effects on cognition compared with placebo, a small increased risk of clinically meaningful cognitive decline occurred in the estrogen plus progestin group.

    View details for Web of Science ID 000183075600025

    View details for PubMedID 12771113

  • A randomized trial of the effect of a plant-based dietary pattern on additional breast cancer events and survival: the Women's Healthy Eating and Living (WHEL) Study CONTROLLED CLINICAL TRIALS Pierce, J. P., Faerber, S., Wright, F. A., Rock, C. L., Newman, V., Flatt, S. W., Kealey, S., Jones, V. E., Caan, B. J., Gold, E. B., Haan, M., Hollenbach, K. A., Jones, L., Marshall, J. R., Ritenbaugh, C., Stefanick, M. L., Thomson, C., Wasserman, L., Natarajan, L., Thomas, R. G., Gilpin, E. A. 2002; 23 (6): 728-756

    Abstract

    The Women's Healthy Eating and Living (WHEL) Study is a multisite randomized controlled trial of the effectiveness of a high-vegetable, low-fat diet, aimed at markedly raising circulating carotenoid concentrations from food sources, in reducing additional breast cancer events and early death in women with early-stage invasive breast cancer (within 4 years of diagnosis). The study randomly assigned 3088 such women to an intensive diet intervention or to a comparison group between 1995 and 2000 and is expected to follow them through 2006. Two thirds of these women were under 55 years of age at randomization. This research study has a coordinating center and seven clinical sites. Randomization was stratified by age, stage of tumor and clinical site. A comprehensive intervention program that includes intensive telephone counseling, cooking classes and print materials helps shift the dietary pattern of women in the intervention. Through an innovative telephone counseling program, dietary counselors encourage women in the intervention group to meet the following daily behavioral targets: five vegetable servings, 16 ounces of vegetable juice, three fruit servings, 30 g of fiber and 15-20% energy from fat. Adherence assessments occur at baseline, 6, 12, 24 or 36, 48 and 72 months. These assessments can include dietary intake (repeated 24-hour dietary recalls and food frequency questionnaire), circulating carotenoid concentrations, physical measures and questionnaires about health symptoms, quality of life, personal habits and lifestyle patterns. Outcome assessments are completed by telephone interview every 6 months with medical record verification. We will assess evidence of effectiveness by the length of the breast cancer event-free interval, as well as by overall survival separately in all the women in the study as well as specifically in women under and over the age of 55 years.

    View details for Web of Science ID 000179835100010

    View details for PubMedID 12505249

  • Menopausal symptoms in older women and the effects of treatment with hormone therapy OBSTETRICS AND GYNECOLOGY Barnabei, V. M., Grady, D., Stovall, D. W., Cauley, J. A., Lin, F., Stuenkel, C. A., Stefanick, M. L., Pickar, J. H. 2002; 100 (6): 1209-1218

    Abstract

    In some women, hot flashes and other symptoms attributed to menopause persist for many years after the cessation of menses. The frequency and severity of such symptoms and response to hormone therapy in older women have not been well documented.We used data from the Heart and Estrogen/Progestin Replacement Study, a blinded, clinical trial among 2763 women with documented coronary disease and a uterus who were randomized to receive either conjugated estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg in one tablet or placebo. Participants were queried at baseline and annually regarding menopausal symptoms. Breast symptoms were self-reported, and uterine bleeding was recorded on a daily diary.Symptoms associated with menopause were relatively common among Heart and Estrogen/Progestin Replacement Study participants, whose average age was 67 years and who averaged 18 years since menopause. At baseline, 16% of women reported frequent hot flashes, 26% vaginal dryness, 10% genital irritation, 55% trouble sleeping, and 53% early awakening. Women assigned to hormone therapy reported less frequent hot flashes, vaginal dryness, and trouble sleeping compared with women assigned to placebo, but more frequent vaginal discharge, genital irritation, uterine bleeding, and breast symptoms. The reporting of breast symptoms among women in the hormone group decreased from 40% at 1 year to 13% by the 4th year. Uterine bleeding was reported by 31% and spotting by an additional 33% of women in the hormone group during the 1st year of treatment; by the 4th year, these proportions had fallen to 11% and 20%, respectively.Symptoms typically attributed to menopause are common in elderly women. Postmenopausal hormone therapy reduces hot flashes, trouble sleeping, and vaginal dryness, but at standard doses in elderly women is associated with vaginal discharge, genital irritation, uterine bleeding, and breast symptoms.

    View details for Web of Science ID 000179526600011

    View details for PubMedID 12468165

  • Obesity, body size, and risk of postmenopausal breast cancer: the Women's Health Initiative (United States) CANCER CAUSES & CONTROL Morimoto, L. M., White, E., Chen, Z., Chlebowski, R. T., Hays, J., Kuller, L., Lopez, A. M., Manson, J., Margolis, K. L., Muti, P. C., Stefanick, M. L., McTiernan, A. 2002; 13 (8): 741-751

    Abstract

    Body size is an important modifiable risk factor for breast cancer. Although obesity has generally been found to be associated with increased risk for postmenopausal breast cancer, there remain questions concerning the role of body fat distribution, lifetime weight history, and effects within specific subgroups of women.We assessed the relationship of several anthropometric measures and risk of postmenopausal breast cancer in 85,917 women aged 50-79 at entry in the Women's Health Initiative Observational Study. Women were enrolled during 1993-1998 at 40 clinics in the US and 1030 developed invasive breast cancer by April 2000. Upon entry, trained clinical center staff measured each woman's height, weight, and waist and hip circumference.Anthropometric factors were not associated with breast cancer among women who had ever used hormone replacement therapy (HRT). Among HRT non-users, heavier women (baseline body mass index (BMI) >31.1) had an elevated risk of postmenopausal breast cancer (relative risk (RR) = 2.52; 95% confidence interval (CI) = 1.62-3.93), compared to slimmer women (baseline BMI < 22.6). The elevation in risk associated with increasing BMI appeared to be most pronounced among younger postmenopausal women. Change in BMI since age 18, maximum BMI, and weight were also associated with breast cancer in HRT non-users. While both waist and hip circumference were associated with breast cancer risk, their ratio, a measure of fat distribution, was not (RR = 1.33; 95% CI = 0.88-2.01).Our study confirms previously reported findings that generalized obesity is an important risk factor for postmenopausal breast cancer, but only among women who have never taken HRT. Lifetime weight gain is also a strong predictor of breast cancer. Waist to hip ratio, a measure of weight distribution, does not appear to be related to postmenopausal breast cancer risk.

    View details for Web of Science ID 000178063700007

    View details for PubMedID 12420953

  • Compliance with national cholesterol education program dietary and lifestyle guidelines among older women with self-reported hypercholesterolemia: The women's health initiative AMERICAN JOURNAL OF MEDICINE Hsia, J., Rodabough, R., Rosal, M. C., Cochrane, B., Howard, B. V., Snetselaar, L., FRISHMAN, W. H., Stefanick, M. L. 2002; 113 (5): 384-392

    Abstract

    Dietary therapy remains the first line of treatment for patients with high blood cholesterol levels. Among free-living persons, compliance with National Cholesterol Education Program (NCEP) dietary recommendations is uncertain.We performed a cross-sectional, baseline analysis of 91,627 postmenopausal women enrolled in the Women's Health Initiative Observational Study. Among women with self-reported hypercholesterolemia, we ascertained factors associated with compliance with National Cholesterol Education Program dietary recommendations, defined for the Step II diet as

    View details for Web of Science ID 000178799400005

    View details for PubMedID 12401533

  • Walking compared with vigorous exercise for the prevention of cardiovascular events in women NEW ENGLAND JOURNAL OF MEDICINE Manson, J. E., Greenland, P., LaCroix, A. Z., Stefanick, M. L., Mouton, C. P., Oberman, A., Perri, M. G., Sheps, D. S., Pettinger, M. B., Siscovick, D. S. 2002; 347 (10): 716-725

    Abstract

    The role of walking, as compared with vigorous exercise, in the prevention of cardiovascular disease remains controversial. Data for women who are members of minority racial or ethnic groups are particularly sparse.We prospectively examined the total physical-activity score, walking, vigorous exercise, and hours spent sitting as predictors of the incidence of coronary events and total cardiovascular events among 73,743 postmenopausal women 50 to 79 years of age in the Women's Health Initiative Observational Study. At base line, participants were free of diagnosed cardiovascular disease and cancer, and all participants completed detailed questionnaires about physical activity. We documented 345 newly diagnosed cases of coronary heart disease and 1551 total cardiovascular events.An increasing physical-activity score had a strong, graded, inverse association with the risk of both coronary events and total cardiovascular events. There were similar findings among white women and black women. Women in increasing quintiles of energy expenditure measured in metabolic equivalents (the MET score) had age-adjusted relative risks of coronary events of 1.00, 0.73, 0.69, 0.68, and 0.47, respectively (P for trend, <0.001). In multivariate analyses, the inverse gradient between the total MET score and the risk of cardiovascular events remained strong (adjusted relative risks for increasing quintiles, 1.00, 0.89, 0.81, 0.78, and 0.72, respectively; P for trend <0.001). Walking and vigorous exercise were associated with similar risk reductions, and the results did not vary substantially according to race, age, or body-mass index. A brisker walking pace and fewer hours spent sitting daily also predicted lower risk.These prospective data indicate that both walking and vigorous exercise are associated with substantial reductions in the incidence of cardiovascular events among postmenopausal women, irrespective of race or ethnic group, age, and body-mass index. Prolonged sitting predicts increased cardiovascular risk.

    View details for Web of Science ID 000177765800003

    View details for PubMedID 12213942

  • Stage of motivational readiness: Predictive ability for exercise behavior AMERICAN JOURNAL OF HEALTH BEHAVIOR Young, D. R., King, A. C., Sheehan, M., Stefanick, M. L. 2002; 26 (5): 331-341

    Abstract

    To determine if stage of motivational readiness for exercise predicted adherence to a 9-month exercise intervention.Three hundred forty-two individuals were randomized into a diet and physical activity trial. The exercise goal was to complete or add at least 10 miles of weekly brisk walking or jogging. Adherence was determined from logs.Sixty-four percent of men and 34% of women reported an increase of at least 10 miles per week. Adherence did not differ by baseline exercise motivational readiness stage.Future work should determine in what contexts stage-targeted interventions are most successful for adoption and maintenance of physical activity.

    View details for Web of Science ID 000177281200002

    View details for PubMedID 12206443

  • Risks and benefits of estrogen plus progestin in healthy postmenopausal women - Principal results from the Women's Health Initiative randomized controlled trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Rossouw, J. E., Anderson, G. L., Prentice, R. L., LaCroix, A. Z., Kooperberg, C., Stefanick, M. L., Jackson, R. D., Beresford, S. A., Howard, B. V., Johnson, K. C., Kotchen, M., Ockene, J. 2002; 288 (3): 321-333

    Abstract

    Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain.To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States.Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998.Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102).The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes.On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years.Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.

    View details for Web of Science ID 000176807000024

    View details for PubMedID 12117397

  • Effects of food availability on serum insulin and lipid concentrations in free-ranging baboons AMERICAN JOURNAL OF PRIMATOLOGY Kemnitz, J. W., Sapolsky, R. M., Altmann, J., Muruthi, P., Mott, G. E., Stefanick, M. L. 2002; 57 (1): 13-19

    Abstract

    The relationship between food availability and metabolic physiology was studied in groups of free-ranging baboons (Papio spp.) living in the Amboseli National Park and the Masai Mara National Reserve of Kenya. Three groups subsisted entirely on natural forage, while two other groups lived near tourist facilities and often consumed food wastes from these lodges. The refuse provided a very accessible food source with relatively high caloric density. Consumption of the refuse was associated with reduced locomotion. Sexually mature individuals from all five groups were sedated surreptitiously in the early morning and blood samples were collected. Compared to animals foraging exclusively in the wild, animals that supplemented their diet with the refuse items had two- to threefold elevations in serum insulin concentrations, as well as increased total cholesterol (C), HDL-C, and VLDL+LDL-C levels. No sex differences in physiological measures were observed except in body mass. Elevated serum insulin, and cholesterol and lipoprotein concentrations influence the development of cardiovascular disease and have been shown to be subject to dietary manipulation and exercise under controlled conditions. The present results suggest potentially deleterious effects of a highly accessible, calorically dense food source, and associated reduction of physical activity for baboons living in an otherwise natural environment.

    View details for DOI 10.1002/ajp.1083

    View details for Web of Science ID 000175326700002

    View details for PubMedID 11977122

  • Men gain additional psychological benefits by adding exercise to a weight-loss program OBESITY RESEARCH Kiernan, M., King, A. C., Stefanick, M. L., Killen, J. D. 2001; 9 (12): 770-777

    Abstract

    Adding exercise to a comprehensive weight-loss program might not only attenuate any psychological distress associated with weight-loss attempts but also may provide psychological benefits. This study examined whether a diet-plus-exercise weight-loss program improved psychological outcomes more than a diet-only weight-loss program or an assessment-only control group.This study was part of a larger 1-year randomized weight-loss trial examining the effects of diet and exercise on cardiovascular disease risk factors in 264 overweight adults. Psychological measures specific to weight control (e.g., cognitive restraint, disinhibition, hunger, and body dissatisfaction) as well as traditional measures of psychological distress (e.g., symptoms of depression, anxiety, and stress) were obtained at baseline and 1 year.Men and women in either weight-loss program reported greater restraint, less disinhibition, and less hunger at 1 year than those in no program. Men in the diet-plus-exercise program experienced additional increases in restraint and decreases in hunger than did men in the diet-only program. Women in the diet-plus-exercise program did not experience additional psychological benefits specific to weight control than those in the diet-only program, despite increases in aerobic capacity.The pattern seen for overweight men in the diet-plus-exercise program at 1 year-greater restraint, less disinhibition, and less hunger-is similar to the pattern seen in successful weight maintainers. These results underscore the need for innovative strategies that will enhance and sustain the pattern of psychological benefits specific to weight control associated with successful weight loss, especially for overweight women.

    View details for Web of Science ID 000172892000006

    View details for PubMedID 11743061

  • Reduction in fat intake is not associated with weight loss in most women alter breast cancer diagnosis - Evidence from a randomized controlled trial CANCER Rock, C. L., Thomson, C., Caan, B. J., Flatt, S. W., Newman, V., Ritenbaugh, C., Marshall, J. R., Hollenbach, K. A., Stefanick, M. L., Pierce, J. P. 2001; 91 (1): 25-34

    Abstract

    A reduction in dietary fat intake has been suggested as a method to promote weight loss in women at risk for breast cancer recurrence.Weight change in response to diet intervention was examined in 1010 women who had completed treatment for Stage I, Stage II, or Stage IIIA (American Joint Committee on Cancer staging system) primary operable breast cancer during their first year of participation in a randomized, controlled, diet intervention trial to reduce risk of recurrence. Diet intervention was performed by telephone counseling and promoted a low fat diet that also was high in fiber, vegetables, and fruit. The comparison group was provided with general dietary guidelines to reduce disease risk. Multiple linear regression models were used to examine the relations among demographic and personal characteristics, changes in diet composition and exercise level, and change in body weight or body mass index.The average weight change in the 1-year period was 0.04 kg for the intervention group and 0.46 kg for the comparison group. For the total group, body weight was stable (+/- 5% baseline weight) for 743 women (74%), whereas 114 (11%) lost weight, and 153 (15%) gained weight. These distributions were similar in the two study groups inclusive of all study participants and for only those women with a baseline body mass index of > or = 25 kg/m2. Initial body mass index and changes in fiber and vegetable intakes, but not change in percent of energy obtained from fat, were associated independently with change in weight or body mass index.For most women at risk for breast cancer recurrence, diet intervention to promote a reduction in fat intake was not associated with significant weight loss. Testing the effect of a substantial change in diet composition on risk for breast cancer recurrence is unlikely to be confounded by weight loss in subjects who were the recipients of intensive intervention efforts.

    View details for Web of Science ID 000168675200004

    View details for PubMedID 11148556

  • Correlates of high HDL cholesterol among women with coronary heart disease AMERICAN HEART JOURNAL Bittner, V., Simon, J. A., Fong, J., Blumenthal, R. S., Newby, K., Stefanick, M. L. 2000; 139 (2): 288-296

    Abstract

    The National Cholesterol Education Program (NCEP) has designated high-density lipoprotein cholesterol (HDL-C) > or =60 mg/dL a "negative" coronary heart disease (CHD) risk factor, but a substantial proportion of coronary events occur among women despite high HDL-C levels.The objective of this study was to characterize postmenopausal women with prevalent CHD despite HDL-C > or =60 mg/dL and to identify factors that may attenuate the protective effect of high HDL-C. We analyzed baseline data from a randomized, double-blind study of estrogen/progestin replacement therapy in 2763 postmenopausal women <80 years old with CHD. Demographics, CHD risk factors, medications, anthropometrics, and lipid levels were compared among women with low, normal, and high HDL-C by NCEP criteria with and without stratification by use of lipid-lowering medications. Independent correlates of high HDL-C were determined by logistic regression analysis. HDL-C > or =60 mg/dL was present in 20% of participants. Women with high HDL-C were older, better educated, had fewer CHD risk factors, lower triglyceride levels and total cholesterol/HDL-C ratio, and were more likely to report past estrogen and current calcium antagonist, niacin, and statin use. beta-Blocker, diuretic, and fibrate use was less common. Older age, alcohol consumption, niacin, and calcium antagonist use and prior estrogen use were independently associated with high HDL-C, whereas waist-to-hip ratio, smoking, triglyceride level, and beta-blocker and fibrate use were inversely associated (all P <.05).High HDL-C, as defined by the NCEP, occurred in 20% of women with CHD in this cohort without a concomitantly higher prevalence of other CHD risk factors. Redefinition of "high" HDL-C levels for women may be warranted.

    View details for Web of Science ID 000085253300014

    View details for PubMedID 10650302

  • Effect of hormone replacement therapy on the validity of the Friedewald equation in postmenopausal women: The Postmenopausal Estrogen/Progestins Interventions (PEPI) trial JOURNAL OF CLINICAL EPIDEMIOLOGY Legault, C., Stefanick, M. L., Miller, V. T., Marcovina, S. M., Schrott, H. G. 1999; 52 (12): 1187-1195

    Abstract

    The Friedewald equation is often used to estimate low-density lipoprotein cholesterol (LDL-C). Hormone therapy is known to raise triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) and alter lipid contents of lipoproteins. We compared Friedewald estimated LDL-C to measured LDL-C in PEPI participants on placebo or four different hormone treatment groups. At baseline, the 0.2 coefficient for triglyceride (TG) was accurate for all five treatment groups. Among women who took >80% of their pills and whose TG was <4.5 mmol/l (400 mg/dl), LDL-C was underestimated for 69-82% of the participants in the active treatment groups, compared to 50% in the placebo group. After 3 years of therapy, the TG coefficient that offered a better fit of the Friedewald equation in the active treatment groups was 0.39 for the equation in mmol/l (0.17 for the equation in mg/dl). Using this coefficient is clearly warranted for greater accuracy in research studies.

    View details for Web of Science ID 000083817000008

    View details for PubMedID 10580781

  • Factors associated with weight gain in women after diagnosis of breast cancer JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION Rock, C. L., Flatt, S. W., Newman, V., Caan, B. J., Haan, M. N., Stefanick, M. L., Faerber, S., Pierce, J. P. 1999; 99 (10): 1212-?

    Abstract

    To identify the factors associated with weight gain after diagnosis of breast cancer in a heterogeneous population of women.Descriptive cross-sectional study.1,116 patients who had been diagnosed with stage I, stage II, or stage IIIA primary, operable breast cancer within the previous 4 years. Patients were recruited during enrollment into a diet intervention trial to reduce risk for breast cancer recurrence. Analysis Demographic data, weight history, and physical activity information obtained by questionnaire and medical information obtained by chart review; dietary assessment based on four 24-hour dietary recalls collected by telephone. Associations between weight change after the diagnosis of breast cancer and prediction variables were examined using univariate and multiple linear regression analyses.Overall, 60% of the subjects reported weight gain, 26% reported weight loss, and 14% reported no change in weight after the diagnosis of breast cancer. The overall mean weight change was a gain of 2.7 kg (6 lb). Factors positively and independently associated with weight gain were time since diagnosis of breast cancer, adjuvant chemotherapy, African-American ethnicity, current energy intake, and postmenopausal status at time of study entry. Factors inversely and independently associated with weight gain were prediagnosis body mass index, age at diagnosis, education level, and exercise index score.Higher energy intake and lower level of physical activity are independently associated with increased risk for weight gain after the diagnosis of breast cancer. Strategies to modify these behaviors are likely to influence the long-term pattern of weight change.

    View details for Web of Science ID 000083014700017

    View details for PubMedID 10524383

  • Effect of postmenopausal hormones on inflammation-sensitive proteins - The Postmenopausal Estrogen/Progestin Interventions (PEPI) Study CIRCULATION Cushman, M., Legault, C., Barrett-Connor, E., Stefanick, M. L., Kessler, C., Judd, H. L., Sakkinen, P. A., Tracy, R. P. 1999; 100 (7): 717-722

    Abstract

    Observational studies in healthy women suggest postmenopausal hormone therapy reduces risk of coronary events. In contrast, in a recent clinical trial of women with coronary disease, a subgroup analysis demonstrated increased risk during the early months of therapy. Because higher levels of inflammation factors predict vascular disease outcomes, the effect of hormones on these factors is of interest.Four inflammation-sensitive factors, C-reactive protein, soluble E-selectin, von Willebrand factor antigen, and coagulation factor VIIIc were measured at baseline, 12, and 36 months in 365 participants of the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial, a randomized, placebo-controlled trial of the effects of 4 hormone preparations on cardiovascular disease risk factors. Compared with placebo, all 4 active preparations resulted in a large sustained increase in the concentration of C-reactive protein and a decrease in soluble E-selectin (P=0.0001). There were no effects of treatment on concentrations of von Willebrand factor or factor VIIIc. There were no differences in effects among treatment arms. Relative to placebo, when combining active treatment arms, final concentrations of C-reactive protein were 85% higher whereas E-selectin was 18% lower compared with baseline.Postmenopausal hormones rapidly increased the concentration of the inflammation factor C-reactive protein. Such an effect may be related to adverse early effects of estrogen therapy. In contrast, hormones reduced the concentration of soluble E-selectin, and this might be considered an anti-inflammatory effect. Because PEPI was not designed to assess clinical endpoints, studies of the impact of hormone-mediated changes in inflammation on risk of subsequent coronary events are needed.

    View details for Web of Science ID 000082082900007

    View details for PubMedID 10449693

  • Knowledge and perceived risk of major diseases in middle-aged and older women HEALTH PSYCHOLOGY Wilcox, S., Stefanick, M. L. 1999; 18 (4): 346-353

    Abstract

    Women's (N = 200; 41-95 years) knowledge of mortality risks and their perceived general risk, personal risk, control, and preventability of coronary heart disease (CHD) and breast, colon, and lung cancer were examined. Middle-aged (MA) women were more accurate in their mortality knowledge for MA men than for MA women and were more accurate for MA than for older (OA) men and women. OA women, in contrast, were least accurate in their mortality knowledge for OA women compared with all other target groups; only 34% knew that CHD is the leading cause of death in OA women. Participants also overestimated a woman's risk of death from breast cancer and underestimated the risk from lung and colon cancer. Ratings of perceived risk, control, and preventability varied as a function of disease. OA women in particular appear to lack knowledge regarding women's risk of major diseases. Results have implications for women's health behaviors and medical decisions.

    View details for Web of Science ID 000081525500004

    View details for PubMedID 10431935

  • Effects of diet and exercise in men and postmenopausal women with low levels of HDL cholesterol and high levels of LDL cholesterol NEW ENGLAND JOURNAL OF MEDICINE Stefanick, M. L., Mackey, S., Sheehan, M., Ellsworth, N., Haskell, W. L., Wood, P. D. 1998; 339 (1): 12-20

    Abstract

    Guidelines established by the National Cholesterol Education Program (NCEP) promote exercise and weight loss for the treatment of abnormal lipoprotein levels. Little is known, however, about the effects of exercise or the NCEP diet, which is moderately low in fat and cholesterol, in persons with lipoprotein levels that place them at high risk for coronary heart disease.We studied plasma lipoprotein levels in 180 postmenopausal women, 45 through 64 years of age, and 197 men, 30 through 64 years of age, who had low high-density lipoprotein (HDL) cholesterol levels (< or =59 mg per deciliter in women and < or =44 mg per deciliter in men) and moderately elevated levels of low-density lipoprotein (LDL) cholesterol (>125 mg per deciliter but <210 mg per deciliter in women and >125 mg per deciliter but <190 mg per deciliter in men). The subjects were randomly assigned to aerobic exercise, the NCEP Step 2 diet, or diet plus exercise, or to a control group, which received no intervention.Dietary intake of fat and cholesterol decreased during the one-year study (P<0.001), as did body weight, in women and men in either the diet group or the diet-plus-exercise group, as compared with the controls (P<0.001) and the exercise group (P<0.05), in which dietary intake and body weight were unchanged. Changes in HDL cholesterol and triglyceride levels and the ratio of total to HDL cholesterol did not differ significantly among the treatment groups, for subjects of either sex. The serum level of LDL cholesterol was significantly reduced among women (a decrease of 14.5+/-22.2 mg per deciliter) and men (a decrease of 20.0+/-17.3 mg per deciliter) in the diet-plus-exercise group, as compared with the control group (women had a decrease of 2.5+/-16.6 mg per deciliter, P<0.05; men had a decrease of 4.6+/-21.1 mg per deciliter, P<0.001). The reduction in LDL cholesterol in men in the diet-plus-exercise group was also significant as compared with that among the men in the exercise group (3.6+/-18.8 mg per deciliter, P<0.001). In contrast, changes in LDL cholesterol levels were not significant among the women (a decrease of 7.3+/-18.9 mg per deciliter) or the men (10.8+/-18.8 mg per deciliter) in the diet group, as compared with the controls.The NCEP Step 2 diet failed to lower LDL cholesterol levels in men or women with high-risk lipoprotein levels who did not engage in aerobic exercise. This finding highlights the importance of physical activity in the treatment of elevated LDL cholesterol levels.

    View details for Web of Science ID 000074500000003

    View details for PubMedID 9647874

  • Characteristics of successful and unsuccessful dieters: An application of signal detection methodology ANNALS OF BEHAVIORAL MEDICINE Kiernan, M., King, A. C., Kraemer, H. C., Stefanick, M. L., Killen, J. D. 1998; 20 (1): 1-6

    Abstract

    Signal detection methods were used to identify predictors of successful weight loss in 177 mildly to moderately overweight women and men assigned to one of two weight-loss programs. Predictors included initial demographic, physiological, behavioral, and psychosocial characteristics, and program type (e.g. diet-only and diet-plus-exercise). Successful weight loss was defined as a loss of at least two units of body mass index at one year. Four subgroups were identified. Participants in the diet-plus-exercise program who were initially more satisfied with their bodies and did not have a history of repeated weight loss were most likely to succeed (63% succeeded). In contrast, participants assigned to the diet-plus-exercise program who were either extremely dissatisfied with their bodies or who had a history of repeated weight loss were at similar risk for failure as participants in the diet-only program (only 26% to 35% succeeded). The results underscore the potential utility of exploring these subgroups further to inform the development of new treatment strategies to increase the likelihood of success.

    View details for Web of Science ID 000075741800001

    View details for PubMedID 9755345

  • Effect of postmenopausal hormone therapy on body weight and waist and hip girths JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Espeland, M. A., Stefanick, M. L., KRITZSILVERSTEIN, D., Fineberg, S. E., Waclawiw, M. A., James, M. K., Greendale, G. A. 1997; 82 (5): 1549-1556

    Abstract

    Reports from cross-sectional comparisons, nonrandomized prospective studies, and relatively small clinical trials indicate that postmenopausal hormone therapy may slightly decrease the amount of weight typically gained by women during the decade following menopause. Despite this, widespread belief remains that hormone therapy may cause weight gain. We use data from the Postmenopausal Estrogen/Progestin Interventions trial to characterize the impact of postmenopausal hormone therapy on weight and fat distribution and to examine the consistency of this impact among subgroups of women defined by lifestyle, clinical, and demographic factors. The Postmenopausal Estrogen/Progestin Interventions trial was a 3-yr, placebo-controlled, randomized clinical trial of 875 women assessing the effects on cardiovascular risk factors of four hormone regimens: oral conjugated equine estrogen (CEE) therapy (0.625 mg daily alone), CEE in combination with medroxyprogesterone acetate (2.5 mg daily), CEE in combination with medroxyprogesterone acetate (10 mg daily on days 1-12), and CEE in combination with micronized progesterone (200 mg daily on days 1-12). Women randomly assigned to CEE with or without a progestational agent averaged 1.0 kg less weight gain at the end of 3 yr (P = 0.006) than those assigned to placebo. Assignment to CEE was also associated with averages of 1.2 cm less increase in waist girth (P = 0.01) and 0.3 cm less increase in hip (P = 0.07) girth. In regression models that included weight change as a covariate, none of these differences reached statistical significance. There were no significant differences in weight or girth changes among any of the four active hormone regimens. After accounting for the effects of assignment to active hormone therapy and baseline weight, older age (P 0.008) and higher physical activity level at baseline (P = 0.002) were also independently predictive of less weight gain. The impact of hormone therapy on weight gain was similar among subgroups, except for those defined by baseline smoking status (P = 0.04) and physical activity level at home (P = 0.02). Factors that were independently associated with smaller increases in girths were: for waist, greater overall activity (P = 0.005) and Hispanic ethnicity (P = 0.02); and for hip, work activity (P = 0.003) and greater alcohol consumption (P = 0.03). None of these factors significantly affected the observed overall relationships between estrogen and changes in girth.

    View details for Web of Science ID A1997WX55100041

    View details for PubMedID 9141548

  • Effects of hormone replacement therapy on endometrial histology in postmenopausal women - The Postmenopausal Estrogen Progestin Interventions (PEPI) trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Judd, H. L., Wasilauskas, C., JOHNSON, S., Merino, M., BARRETTCONNOR, E., Trabal, J., Miller, V. T., Barnabei, V., Levin, G., Bush, T., Foster, D., Zacur, H., Woodruff, J. D., Stefanick, M., AKANA, A., Heinrichs, W. L., OHANLAN, K., Buyalos, R. P., Greendale, G., Lozano, K., CarrionPetersen, L., CAVERO, C., Langer, R., Schrott, H. G., Benda, J. A., DEPROSSE, C., Fedderson, D., Johnson, S. R., Ahmad, M. M., Brown, H. P., Schenken, R. S., RODRIGUEZSIFUENTES, M., VALENTE, P. T., Espeland, M., Lane, K., Legault, C., MEBANESIMS, I. L., Kelaghan, J., McGowan, J., Fradkin, J., Sherman, S., Scully, R. 1996; 275 (5): 370-375
  • DISTRIBUTION AND CORRELATES OF PLASMA-FIBRINOGEN IN MIDDLE-AGED WOMEN - INITIAL FINDINGS OF THE POSTMENOPAUSAL ESTROGEN-PROGESTIN INTERVENTIONS (PEPI) STUDY ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY Stefanick, M. L., Legault, C., Tracy, R. P., Howard, G., Kessler, C. M., Lucas, D. L., Bush, T. L. 1995; 15 (12): 2085-2093

    Abstract

    Fibrinogen levels have been reported in cohort and case-control studies to be positively related to the development of coronary heart disease. This report presents the distribution and determinants of fibrinogen in women enrolling in a 3-year randomized trial of hormone replacement therapy (HRT), the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. Fasting plasma fibrinogen levels were measured in 874 postmenopausal women, aged 45 to 65 years, who had not used HRT for at least 3.5 months. Mean (+/- SD) fibrinogen level was 2.83 +/- 0.45 g/L. There was a significant positive association between fibrinogen and age (P = .03). Significantly higher (P < .005) fibrinogen levels were seen in current smokers versus nonsmokers (2.94 versus 2.81 g/L), in women who reported consuming fewer than 12 alcoholic drinks in the 12 months before the baseline visit versus higher consumption (2.90 versus 2.79 g/L), and in women who reported never versus ever having used HRT (2.90 versus 2.77 g/L). Self-reported leisure time physical activity (LTPA) was negatively associated (P = .0001) with fibrinogen levels as follows: inactive (2.84 g/L), light (2.89 g/L), moderate (2.80 g/L), and heavy (2.60 g/L), with significantly (P = .0001) lower levels in women who reported heavy LTPA versus each of the other categories and in women reporting moderate versus light LTPA. A strong positive correlation was found between fibrinogen and body mass index (BMI) (r = .32; P < .0001). In a model that included age, smoking, alcohol intake, prior HRT, LTPA, and BMI, LTPA was no longer a statistically significant predictor of fibrinogen level, while associations with other variables remained significant.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1995TJ36800001

    View details for PubMedID 7489228

  • PHYSICAL AND LABORATORY MEASUREMENTS IN THE PEPI TRIAL CONTROLLED CLINICAL TRIALS Wood, P. D., Kessler, G., Lippel, K., Stefanick, M. L., Wasilauskas, C. H., Wells, H. B. 1995; 16 (4): S36-S53
  • Physical and laboratory measurements in the PEPI Trial Postmenopausal Estrogen/Progestin Interventions. Controlled clinical trials Wood, P. D., Kessler, G., Lippel, K., Stefanick, M. L., Wasilauskas, C. H., Wells, H. B. 1995; 16 (4): 36S-53S

    View details for PubMedID 7587219

  • RATIONALE, DESIGN, AND CONDUCT OF THE PEPI TRIAL CONTROLLED CLINICAL TRIALS Espeland, M. A., Bush, T. L., MEBANESIMS, I., Stefanick, M. L., JOHNSON, S., Sherwin, R., Waclawiw, M. 1995; 16 (4): S3-S19
  • Rationale, design, and conduct of the PEPI Trial. Postmenopausal Estrogen/Progestin Interventions. Controlled clinical trials Espeland, M. A., Bush, T. L., Mebane-Sims, I., Stefanick, M. L., JOHNSON, S., Sherwin, R., Waclawiw, M. 1995; 16 (4): 3S-19S

    Abstract

    There is growing and consistent evidence that estrogen use in postmenopausal women is associated with a substantial reduction in the occurrence of cardiovascular disease. However, remarkably little is known about the biological mechanisms by which estrogen therapy may influence risk. Even less information is available on the cardiovascular effects of combined estrogen-progestin use. PEPI was not designed to test whether estrogen and estrogen-progestin therapy is efficacious in the prevention of cardiovascular disease, as a much larger trial with clinical disease outcomes is needed to answer that question. However, PEPI will provide critical evidence regarding the potential effectiveness of the various estrogen and estrogen/progestin regimens ni altering risk factors for cardiovascular disease in women. Detailed information on factors such as adherence, side effects, and general patient acceptability will also be ascertained. The main results from PEPI will provide the scientific community with information on the basic actions of estrogen and estrogen/progestin therapy on four biological systems believed to be causally associated with cardiovascular disease occurrence. Further, since the trial is designed to continue for 3 years, PEPI will be able to provide information on longer term as well as short-term effects on these systems. Finally, the results from PEPI should enable women and their physicians to select an optimal hormonal regimen, i.e., one that is acceptable, safe, and provides the most beneficial and least deleterious changes in cardiovascular and other risk factors.

    View details for PubMedID 7587218

  • LONG-TERM EFFECTS OF VARYING INTENSITIES AND FORMATS OF PHYSICAL-ACTIVITY ON PARTICIPATION RATES, FITNESS, AND LIPOPROTEINS IN MEN AND WOMEN AGED 50 TO 65 YEARS CIRCULATION King, A. C., Haskell, W. L., Young, D. R., Oka, R. K., Stefanick, M. L. 1995; 91 (10): 2596-2604

    Abstract

    Although exercise parameters such as intensity and format have been shown to influence exercise participation rates and physiological outcomes in the short term, few data are available evaluating their longer-term effects. The study objective was to determine the 2-year effects of differing intensities and formats of endurance exercise on exercise participation rates, fitness, and plasma HDL cholesterol levels among healthy older adults.Higher-intensity, group-based exercise training; higher-intensity, home-based exercise; and lower-intensity, home-based exercise were compared in a 2-year randomized trial. Participants were 149 men and 120 postmenopausal women 50 to 65 years of age who were sedentary and free of cardiovascular disease. Recruitment was achieved through a random digit-dial community telephone survey and media promotion. All exercise occurred in community settings. For higher-intensity exercise training, three 40-minute endurance training sessions per week were prescribed at 73% to 88% of peak treadmill heart rate. For lower-intensity exercise, five 30-minute endurance training sessions per week were prescribed at 60% to 73% of peak treadmill heart rate. Treadmill exercise performance, lipoprotein levels and other heart disease risk factors, and exercise adherence were evaluated at baseline and across the 2-year period. Treadmill exercise test performance improved for all three training conditions during year 1 and was successfully maintained during year 2, particularly for subjects in the higher-intensity, home-based condition. Subjects in that condition also showed the greatest year 2 exercise adherence rates (P < .003). Although no significant increases in HDL cholesterol were observed during year 1, by the end of year 2 subjects in the two home-based training conditions showed small but significant HDL cholesterol increases over baseline (P < .01). The increases were particularly pronounced for subjects in the lower-intensity condition, whose exercise prescription required more frequent exercise sessions per week. For all exercise conditions, increases in HDL cholesterol were associated with decreases in waist-to-hip ratio in both men and women (P < .04).While older adults can benefit from initiating a regular regimen of moderate-intensity exercise in terms of improved fitness levels and small improvements in HDL cholesterol levels, the time frame needed to achieve HDL cholesterol change (2 years) may be longer than that reported previously for younger populations. Frequency of participation may be particularly important for achieving such changes. Supervised home-based exercise regimens represent a safe, attractive alternative for achieving sustained participation.

    View details for Web of Science ID A1995QX58700017

    View details for PubMedID 7743622

  • EFFECTS OF ESTROGEN OR ESTROGEN/PROGESTIN REGIMENS ON HEART-DISEASE RISK-FACTORS IN POSTMENOPAUSAL WOMEN - THE POSTMENOPAUSAL ESTROGEN/PROGESTIN INTERVENTIONS (PEPI) TRIAL JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Miller, V. T., LaRosa, J., Barnabei, V., Kessler, C., Levin, G., SMITHROTH, A., Griffin, M., Stoy, D. B., Bush, T., Zacur, H., Foster, D., Anderson, J., McKenzie, A., Miller, S., Wood, P. D., Stefanick, M. L., Marcus, R., AKANA, A., Heinrichs, L., Kirchner, C., OHANLAN, K., Ruyle, M., Sheehan, M., Judd, H. L., Greendale, G., BAYALOS, R., Lozano, K., Kawakami, K., BARRETTCONNOR, E., Langer, R., KRITZSILVERSTEIN, D., CARRIONPETERSEN, M. L., CAVERO, C., Schrott, H. G., Johnson, S. R., FEDDERSEN, D. A., KRUTZFELDT, D. L., Benda, J. A., PAUERSTEIN, C., Trabal, J., Schenken, R., Stern, M. P., RODRIGUEZSIFUENTES, M., Easton, C., Wells, H. B., Espeland, M., Howard, G., Byington, R., Legault, C., Shumaker, S., Hogan, P., HIRE, D., Wasilauskas, C., James, M., Lane, K., Terrell, T., Reece, S., Pierce, J., Snow, M., Anthony, S., MEBANESIMS, I. L., Einhorn, P., Hunsberger, S., Waclawiw, M., Lippel, K., Lucas, D., Verter, J., Jackson, S., Kelaghan, J., Perlman, J., Wolf, P., McGowan, J., GORDON, S., Heyse, S., Fradkin, J., Sherman, S., Page, L., Sorenson, A., Hulka, B., Brody, B., Burkman, R., Heaney, R., Krauss, R., Roberts, H., Wittes, J., Riggs, L., Moss, R., Albers, J., Marcovina, S., Fineberg, S. E., Tracy, R. P., Merino, M., Scully, R., Livolsi, V., Kessler, G. 1995; 273 (3): 199-208

    Abstract

    To assess pairwise differences between placebo, unopposed estrogen, and each of three estrogen/progestin regimens on selected heart disease risk factors in healthy postmenopausal women.A 3-year, multicenter, randomized, double-blind, placebo-controlled trial.A total of 875 healthy postmenopausal women aged 45 to 64 years who had no known contraindication to hormone therapy.Participants were randomly assigned in equal numbers to the following groups: (1) placebo; (2) conjugated equine estrogen (CEE), 0.625 mg/d; (3) CEE, 0.625 mg/d plus cyclic medroxyprogesterone acetate (MPA), 10 mg/d for 12 d/mo; (4) CEE, 0.625 mg/d plus consecutive MPA, 2.5 mg/d; or (5) CEE, 0.625 mg/d plus cyclic micronized progesterone (MP), 200 mg/d for 12 d/mo. PRIMARY ENDPOINTS: Four endpoints were chosen to represent four biological systems related to the risk of cardiovascular disease: (1) high-density lipoprotein cholesterol (HDL-C), (2) systolic blood pressure, (3) serum insulin, and (4) fibrinogen.Analyses presented are by intention to treat. P values for primary endpoints are adjusted for multiple comparisons; 95% confidence intervals around estimated effects were calculated without this adjustment.Mean changes in HDL-C segregated treatment regimens into three statistically distinct groups: (1) placebo (decrease of 0.03 mmol/L [1.2 mg/dL]); (2) MPA regimens (increases of 0.03 to 0.04 mmol/L [1.2 to 1.6 mg/dL]); and (3) CEE with cyclic MP (increase of 0.11 mmol/L [4.1 mg/dL]) and CEE alone (increase of 0.14 mmol/L [5.6 mg/dL]). Active treatments decreased mean low-density lipoprotein cholesterol (0.37 to 0.46 mmol/L [14.5 to 17.7 mg/dL]) and increased mean triglyceride (0.13 to 0.15 mmol/L [11.4 to 13.7 mg/dL]) compared with placebo. Placebo was associated with a significantly greater increase in mean fibrinogen than any active treatment (0.10 g/L compared with -0.02 to 0.06 g/L); differences among active treatments were not significant. Systolic blood pressure increased and postchallenge insulin levels decreased during the trial, but neither varied significantly by treatment assignment. Compared with other active treatments, unopposed estrogen was associated with a significantly increased risk of adenomatous or atypical hyperplasia (34% vs 1%) and of hysterectomy (6% vs 1%). No other adverse effect differed by treatment assignment or hysterectomy status.Estrogen alone or in combination with a progestin improves lipoproteins and lowers fibrinogen levels without detectable effects on postchallenge insulin or blood pressure. Unopposed estrogen is the optimal regimen for elevation of HDL-C, but the high rate of endometrial hyperplasia restricts use to women without a uterus. In women with a uterus, CEE with cyclic MP has the most favorable effect on HDL-C and no excess risk of endometrial hyperplasia.

    View details for Web of Science ID A1995QB23400023

    View details for PubMedID 7807658

  • THE EFFECTS OF WEIGHT-LOSS BY EXERCISE OR BY DIETING ON PLASMA HIGH-DENSITY-LIPOPROTEIN (HDL) LEVELS IN MEN WITH LOW, INTERMEDIATE, AND NORMAL-TO-HIGH HDL AT BASE-LINE METABOLISM-CLINICAL AND EXPERIMENTAL Williams, P. T., Stefanick, M. L., Vranizan, K. M., Wood, P. D. 1994; 43 (7): 917-924

    Abstract

    To assess whether baseline plasma high-density lipoprotein (HDL) cholesterol levels affected the HDL response to weight loss, we examined lipoprotein changes in overweight men aged 30 to 59 years who were randomized to lose weight by exercise training (primarily running, n = 46) or by caloric restriction (ie, dieting, n = 42) or to remain sedentary, nondieting controls (n = 42) in a 1-year study. In exercisers, absolute increases in HDL (mg/dL) were greatest in men with normal-to-high baseline HDL and least in men with low baseline HDL. Specifically, when divided into groups of low (< or = 37 mg/dL), intermediate (38 to 47 mg/dL), and normal-to-high HDL cholesterol (> or = 48 mg/dL) at baseline, the exercisers increased HDL cholesterol by 2.3 +/- 1.9, 4.9 +/- 1.1, and 7.0 +/- 1.3 mg/dL, respectively; HDL2 cholesterol by 0.8 +/- 1.6, 2.3 +/- 1.2, and 5.1 +/- 1.3 mg/dL; and HDL2 mass by 2.8 +/- 5.1, 9.5 +/- 8.9, and 31.7 +/- 11.0 mg/dL. Relative increases in HDL cholesterol were more similar in the low (7.1% +/- 6.1%), intermediate (12.4% +/- 3.9%), and normal-to-high men (13.2% +/- 4.0%). Regression analyses were performed to assess whether baseline HDL cholesterol was related to the amount of absolute HDL change per unit of weight loss. In exercisers, the increase in HDL3 cholesterol concentrations was significantly greater in men with low HDL than in those with normal-to-high HDL at entry (2.0 +/- 0.8 v 0.2 +/- 0.8 mg/dL per kg/m2 lost).(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1994NV98400022

    View details for PubMedID 8028519

  • EFFECTS OF LOW-FAT DIET, CALORIE RESTRICTION, AND RUNNING ON LIPOPROTEIN SUBFRACTION CONCENTRATIONS IN MODERATELY OVERWEIGHT MEN METABOLISM-CLINICAL AND EXPERIMENTAL Williams, P. T., Krauss, R. M., Stefanick, M. L., Vranizan, K. M., Wood, P. D. 1994; 43 (5): 655-663

    Abstract

    We studied the effects of exercise (primarily running), calorie restriction (dieting), and a low-fat, high-carbohydrate diet on changes in lipoprotein subfractions in moderately overweight men in a randomized controlled clinical trial. After 1 year, complete data were obtained for 39 men assigned to lose weight through dieting without exercise, 37 men assigned to lose weight through dieting with exercise (primarily running), and 40 nondieting sedentary controls. We instructed both diet groups to consume no more than 30% total fat, 10% saturated fat, and 300 mg/d of cholesterol, and at least 55% carbohydrates, and the controls were instructed to maintain their usual food choices. Analytic ultracentrifugation was used to measure changes in plasma lipoprotein mass concentrations. In addition, the absorbance of protein-stained polyacrylamide gradient gels was used as an index of concentrations for five high-density lipoprotein (HDL) subclasses that have been identified by their particle sizes, ie, HDL3c (7.2 to 7.8 nm), HDL3b (7.8 to 8.2 nm), HDL3a (8.2 to 8.8 nm), HDL2a (8.8 to 9.7 nm), and HDL2b (9.7 to 12 nm). Relative to controls, weight decreased significantly in men who dieted with exercise (net difference +/- SE, -3.3 +/- 0.4 kg/m2) and in men who dieted without exercise (-2.0 +/- 0.4 kg/m2). Dieting with exercise significantly decreased very-low-density lipoprotein (VLDL)-mass concentrations and significantly increased plasma HDL2-mass, HDL3a, HDL2a, and HDL2b relative to both control and dieting without exercise. There were no significant changes in lipoprotein mass and HDL protein for dieters who did not run.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1994NL24400021

    View details for PubMedID 8177056

  • Exercise and weight control. Exercise and sport sciences reviews Stefanick, M. L. 1993; 21: 363-396

    Abstract

    Several important questions need to be answered to increase the likelihood that exercise will be accepted by the millions in the population who are obese. What is the minimum exercise "dose" (intensity, duration, frequency) and what is the optimal mode to bring about substantial fat weight loss, with minimal loss of lean mass? What is the best nutritional plan to optimize fat utilization during exercise, without impairing performance or loss of lean mass? Which diet and exercise programs maximally increase utilization of centrally deposited fat and how can hyperplastic obesity best be treated? Also of interest is the potential role of resistance exercise for weight loss, and the predictors of weight loss success. For instance, do individuals with gynoid obesity really differ from individuals with android obesity in their utilization and loss of body fat during exercise? The potential advantages of exercise include: stimulation of fat as opposed to carbohydrate oxidation; increased energy use during the exercise itself and in the postexercise period; protection of lean body mass; possible reversal of the diet-induced suppression of BMR; and other health benefits. Among other parameters, the effectiveness of exercise on weight loss may be influenced by the type, intensity, frequency, and duration of exercise bouts and the duration of the training program, the nature of the excess fat stores, i.e., whether the person has obesity characterized by hyperplastic or hypertrophic adipose tissue or central (with large-intra-abdominal depot) or peripheral obesity, the composition and caloric content of the diet, and behavioral aspects that affect adherence to the program. With respect to this latter concern, even if a person has been very successful at weight loss in a metabolic ward or intensive program, he/she must eventually return to the outside world and figure out for himself/herself how to eat real food and/or maintain an activity level that promotes weight maintenance. Because diet and exercise habits are difficult to assess and to quantify in free-living populations, it continues to be difficult to evaluate the success of diet and/or exercise prescriptions for weight loss accurately and we continue to be plagued with questions regarding the effectiveness vs. efficacy of exercise as a means to control body weight. It would seem that the wide range of health benefits derived from regular exercise would justify emphasizing increased activity for inactive people, particularly for obese, sedentary individuals, whether or not ideal body weight or significant weight loss is achieved.

    View details for PubMedID 8504848

  • ASSOCIATIONS OF LIPOPROTEINS AND APOLIPOPROTEINS WITH GRADIENT GEL-ELECTROPHORESIS ESTIMATES OF HIGH-DENSITY-LIPOPROTEIN SUBFRACTIONS IN MEN AND WOMEN ARTERIOSCLEROSIS AND THROMBOSIS Williams, P. T., Krauss, R. M., Vranizan, K. M., Stefanick, M. L., WOOD, P. D., LINDGREN, F. T. 1992; 12 (3): 332-340

    Abstract

    We examined the relations of gender and lipoproteins to subclasses of high density lipoproteins (HDLs) in a cross-sectional sample of moderately overweight men (n = 116) and women (n = 78). The absorbance of protein-stained polyacrylamide gradient gels was used as an index of mass concentrations of HDL at intervals of 0.01 nm across the entire HDL particle size range (7.2-12 nm). At least five HDL subclasses have been identified by their particle sizes: HDL3c (7.2-7.8 nm), HDL3b (7.8-8.2 nm), HDL3a (8.2-8.8 nm), HDL2a (8.8-9.7 nm), and HDL2b (9.7-12 nm). Men had significantly higher HDL3b and significantly lower HDL2a and HDL2b than did women. Correlations of HDL subclasses with concentrations of other lipoprotein variables were generally as strong for gradient gel electrophoresis as for analytical ultracentrifugation measurements of HDL particle distributions. In both sexes, high levels of HDL3b were associated with coronary heart disease risk factors, including high concentrations of triglycerides, apolipoprotein B, small low density lipoproteins, intermediate density lipoproteins, and very low density lipoproteins and low concentrations of HDL2 cholesterol and HDL2 mass. Plasma concentrations of HDL3 cholesterol were unrelated to protein-stained HDL3b levels. HDL3 cholesterol concentrations also did not exhibit the sex difference or the relations with lipoprotein concentrations that characterized HDL3b. Thus, low HDL3b levels may contribute in part to the low heart disease risk in men and women who have high HDL cholesterol. Measurements of HDL3 cholesterol may not identify clinically important relations involving HDL3b.

    View details for Web of Science ID A1992HJ91600010

    View details for PubMedID 1547192

  • HORMONES AND SEXUAL-BEHAVIOR IN RELATIONSHIP TO AGING IN MALE-RATS HORMONES AND BEHAVIOR Smith, E. R., Stefanick, M. L., Clark, J. T., DAVIDSON, J. M. 1992; 26 (1): 110-135

    Abstract

    To determine if the age-related decline in male sex behavior is correlated with hormonal factors, a longitudinal study was conducted. Sexually experienced males were given mating tests every 2 months from 7 through 27 months of age. To study possible relationships between changes in behavior and alterations in hormone levels, blood samples were taken before and after these bimonthly tests. At 23 months, cross-sectional studies were also conducted comparing results to those obtained in 5-month-old males. Significant changes in mating behavior first appeared at 11 months; mount latency, intromission latency, ejaculation latency, postejaculatory interval, and intercopulatory interval were increased. Similarly, detectable decreases in testosterone (T) also occurred at this age. A significant decline in luteinizing hormone (LH) was not seen until 19 months. Correlational analyses revealed small (r less than or equal to -0.29) but significant negative correlations between T and parameters of mating behavior with age. When each age was examined separately, no significant correlations appeared. Plasma T was not predictive of behavioral performance. At 23 months, cross-sectional studies revealed deficits in mounting and penile reflex behavior but ejaculatory reflex capacity was unimpaired. At 28 months, males were decapitated. Only T levels showed a significant effect of age; estradiol, prolactin, and LH were unaffected when compared to 5-month-old males. The data suggest that although there are small and significant negative correlations between circulating testosterone and parameters of mating behavior with advancing age, it is unlikely that the observed decline in testosterone is the primary cause of the age-induced behavioral deficits. It is likely that the major causal factor(s) involves non-hormone-dependent changes within the CNS.

    View details for Web of Science ID A1992HJ94600009

    View details for PubMedID 1563724

  • THE EFFECTS ON PLASMA-LIPOPROTEINS OF A PRUDENT WEIGHT-REDUCING DIET, WITH OR WITHOUT EXERCISE, IN OVERWEIGHT MEN AND WOMEN NEW ENGLAND JOURNAL OF MEDICINE Wood, P. D., Stefanick, M. L., Williams, P. T., Haskell, W. L. 1991; 325 (7): 461-466

    Abstract

    The National Cholesterol Education Program (NCEP) recommends a low-saturated-fat, low-cholesterol diet, with weight loss if indicated, to correct elevated plasma cholesterol levels. Weight loss accomplished by simple caloric restriction or increased exercise typically increases the level of high-density lipoprotein (HDL) cholesterol. Little is known about the effects on plasma lipoproteins of a hypocaloric NCEP diet with or without exercise in overweight people.We tested the hypothesis that exercise (walking or jogging) will increase HDL cholesterol levels in moderately overweight, sedentary people who adopt a hypocaloric NCEP diet. We randomly assigned 132 men and 132 women 25 to 49 years old to one of three groups: control, hypocaloric NCEP diet, or hypocaloric NCEP diet with exercise. One hundred nineteen of the men and 112 of the women returned for testing after one year.After one year, the subjects in both intervention groups had reached or closely approached NCEP Step 1 dietary goals and reduced their mean body fat significantly (range of reduction in mean fat weight, 4.0 to 7.8 kg). Weight loss on the NCEP diet alone did not significantly change HDL cholesterol levels in either the men or the women as compared with the subjects in the control group. Plasma levels of HDL cholesterol increased significantly more in the men who exercised and dieted (mean [+/- SE] change, +13 +/- 3 percent) than in the men who only dieted (+2 +/- 3 percent, P less than 0.01) or the men who acted as controls (-4 +/- 2 percent, P less than 0.001). HDL cholesterol levels remained about the same in the women who exercised and dieted (+1 +/- 2 percent); they were higher than in the women who only dieted (-10 +/- 3 percent, P less than 0.01), but not higher than in the controls (-3 +/- 3 percent).Regular exercise in overweight men and women enhances the improvement in plasma lipoprotein levels that results from the adoption of a low-saturated-fat, low-cholesterol diet.

    View details for Web of Science ID A1991GA76300003

    View details for PubMedID 1852180

  • CONTRIBUTIONS OF REGIONAL ADIPOSE-TISSUE DEPOTS TO PLASMA-LIPOPROTEIN CONCENTRATIONS IN OVERWEIGHT MEN AND WOMEN - POSSIBLE PROTECTIVE EFFECTS OF THIGH FAT METABOLISM-CLINICAL AND EXPERIMENTAL Terry, R. B., Stefanick, M. L., Haskell, W. L., Wood, P. D. 1991; 40 (7): 733-740

    Abstract

    Anthropometry and dual-photon absorptiometry (DPA) were used to examine associations of regional adiposity with plasma lipid, lipoprotein, and lipoprotein subfraction mass concentrations in moderately overweight men and women. Among 130 women, waist to thigh girth ratio (WTR) correlated with triglycerides (TG) (r = .33, P less than .0001) and negatively with high-density lipoprotein (HDL)-cholesterol (HDL-C) (r = -.37, P less than .0001) concentration, as expected. While WTR did not correlate with low-density lipoprotein (LDL)-cholesterol (LDL-C) it correlated positively with the mass subfraction of small (Sfo, 0 to 7) LDL (r = .38, P less than .0001), and negatively with large (Sfo, 7 to 12) LDL (r = -.31, P less than .01). Among 133 men, similar though weaker relationships were found. Thigh girth correlated positively with HDL and HDL2-C and mass, and with LDL particle size among women. Multivariate analysis suggests that association of WTR with lipoprotein values known to carry risk of coronary heart disease (CHD) are due at least as much to effects of thigh girth as to deleterious effects of waist girth. Estimates of fat weight in thigh and abdominal regions by DPA support thigh fat as contributing to these effects of thigh girth. Thigh fat may contribute to lipoprotein profiles that predict lower risk of cardiovascular disease.

    View details for Web of Science ID A1991FV09000014

    View details for PubMedID 1870428

  • INSULIN RESISTANCE AND HYPERTRIGLYCERIDEMIA IN NONDIABETIC RELATIVES OF PATIENTS WITH NONINSULIN-DEPENDENT DIABETES-MELLITUS JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Laws, A., Stefanick, M. L., Reaven, G. M. 1989; 69 (2): 343-347

    Abstract

    Plasma glucose, FFA, and insulin responses to an oral glucose challenge, plasma lipid and lipoprotein concentrations, and the ability of insulin to stimulate glucose disposal were measured in 35 nondiabetic sedentary and overweight subjects. The subjects were divided into 2 groups on the basis of the presence (n = 19) or absence (n = 16) of a history of a first degree relative with noninsulin-dependent diabetes. The 2 groups were similar in age, body mass index, waist to hip ratio, and maximal aerobic capacity. The results demonstrated that the ability of insulin to stimulate disposal of a glucose load was significantly reduced in the subjects with a positive family history of noninsulin-dependent diabetes. In addition, these individuals had significantly higher plasma triglyceride and very low density lipoprotein cholesterol concentrations. Since all environmental factors known to modify insulin action and very low density lipoprotein metabolism were equal in the 2 groups, these data suggest that the metabolic differences noted are likely to be genetic in origin.

    View details for Web of Science ID A1989AF97500020

    View details for PubMedID 2666429

  • REGIONAL ADIPOSITY PATTERNS IN RELATION TO LIPIDS, LIPOPROTEIN CHOLESTEROL, AND LIPOPROTEIN SUBFRACTION MASS IN MEN JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Terry, R. B., Wood, P. D., Haskell, W. L., Stefanick, M. L., Krauss, R. M. 1989; 68 (1): 191-199

    Abstract

    Anatomical adipose tissue distribution patterns are reported to relate to plasma lipids and risk of cardiovascular disease. Waist to hip girth ratios (WHR) and subscapular 10 triceps skinfold thickness ratios (STR) were compared with percent body fat and body mass index values as correlates of plasma lipids and lipoprotein cholesterol and serum lipoprotein subfraction mass by analytic ultracentrifugation in 81 sedentary middle-aged men in a typical range of adiposity. WHR was significantly and positively correlated with plasma concentrations of triglycerides, cholesterol, and low and very low density lipoprotein (LDL and VLDL) cholesterol and inversely correlated with high density lipoprotein (HDL) cholesterol. STR followed these trends, though less strongly, in relation to plasma triglycerides, VLDL cholesterol, and HDL cholesterol. Pronounced differences were found between regional adiposity patterns in their relationships to lipoprotein subfractions, as determined by analytic ultracentrifugation. WHR was negatively correlated with HDL2 (flotation rate F(1.2) 3.5-9), positively with small LDL (S.f 0-7), intermediate density lipoprotein (S.f 12-20), and VLDL (S.f 20-400), while STR correlated with larger LDL (S.f 7-12) and larger VLDL (S.f 60-400). Overall adiposity was not significantly associated with plasma lipoprotein levels after adjusting for regional adiposity patterns. Plasma sex hormone-binding globulin and percent free testosterone were associated with regional adiposity, but did not account for the correlations between WHR and lipoproteins. WHR and STR are measures of fat distribution that correlate with plasma lipoprotein profiles consistent with cardiovascular disease risk and have different relationships to lipoprotein mass subfractions.

    View details for Web of Science ID A1989R678200031

    View details for PubMedID 2909551

  • CHANGES IN PLASMA-LIPIDS AND LIPOPROTEINS IN OVERWEIGHT MEN DURING WEIGHT-LOSS THROUGH DIETING AS COMPARED WITH EXERCISE NEW ENGLAND JOURNAL OF MEDICINE Wood, P. D., Stefanick, M. L., Dreon, D. M., FREYHEWITT, B., GARAY, S. C., Williams, P. T., Superko, H. R., Fortmann, S. P., Albers, J. J., Vranizan, K. M., ELLSWORTH, N. M., Terry, R. B., Haskell, W. L. 1988; 319 (18): 1173-1179

    Abstract

    We studied separately the influence of two methods for losing fat weight on the levels of plasma lipids and lipoproteins in overweight sedentary men--decreasing energy intake without increasing exercise (diet), and increasing energy expenditure without altering energy intake (exercise, primarily running)--in a one-year randomized controlled trial. As compared with controls (n = 42), dieters (n = 42) had significant loss of total body weight (-7.8 +/- 0.9 kg [mean +/- SE]), fat weight (-5.6 +/- 0.8 kg), and lean (non-fat) weight (-2.1 +/- 0.5 kg) (P less than 0.001 for each variable), and exercisers (n = 47) had significant loss of total body weight (-4.6 +/- 0.8 kg) and fat weight (-3.8 +/- 0.7 kg) (P less than 0.001 for both variables) but not lean weight (-0.7 +/- 0.4 kg). Fat-weight loss did not differ significantly between dieters and exercisers. All subjects were discouraged from altering their diet composition; however, dieters and exercisers had slight reductions in the percentage of kilojoules derived from fat. As compared with the control group, both weight-loss groups had significant increases (P less than 0.01) in plasma concentrations of high-density lipoprotein (HDL) cholesterol (diet vs. exercise, 0.13 +/- 0.03 vs. 0.12 +/- 0.03 mmol per liter), HDL2 cholesterol (0.07 +/- 0.02 vs. 0.07 +/- 0.02 mmol per liter), and HDL3 cholesterol (0.07 +/- 0.02 vs. 0.06 +/- 0.02 mmol per liter) and significant decreases (P less than 0.05) in triglyceride levels (diet vs. exercise, -0.35 +/- 0.14 vs. -0.24 +/- 0.12 mmol per liter). Levels of total and low-density lipoprotein cholesterol were not significantly changed, relative to values in controls. None of these changes were significantly different between dieters and exercisers. Thus, we conclude that fat loss through dieting or exercising produces comparable and favorable changes in plasma lipoprotein concentrations.

    View details for Web of Science ID A1988Q697500001

    View details for PubMedID 3173455

  • THE EFFECT OF ACTIVE WEIGHT-LOSS ACHIEVED BY DIETING VERSUS EXERCISE ON POSTHEPARIN HEPATIC AND LIPOPROTEIN-LIPASE ACTIVITY ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Stefanick, M. L., FREYHEWITT, B., Hoover, C. A., Terry, R. B., Wood, P. D. 1987; 499: 338-339
  • RELATIONSHIPS OF PLASMA ESTRADIOL, TESTOSTERONE, AND SEX HORMONE-BINDING GLOBULIN WITH LIPOPROTEINS, APOLIPOPROTEINS, AND HIGH-DENSITY-LIPOPROTEIN SUBFRACTIONS IN MEN JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Stefanick, M. L., Williams, P. T., Krauss, R. M., Terry, R. B., Vranizan, K. M., Wood, P. D. 1987; 64 (4): 723-729

    Abstract

    Plasma estradiol, testosterone, and sex hormone-binding globulin (SHBG) were studied in relation to plasma lipoproteins, high density lipoprotein (HDL) subfractions, and apolipoproteins in 73 healthy but sedentary middle-aged men. Among potentially confounding variables, a strong positive association was found between estradiol levels and cigarette use, while testosterone and SHBG correlated negatively with percent body fat and alcohol intake. After adjustment for smoking, percent body fat, and alcohol, plasma estradiol levels correlated negatively with total cholesterol and low density lipoprotein cholesterol, and testosterone levels correlated positively with apolipoprotein B, while SHBG levels correlated positively with HDL2 mass and apolipoprotein A-I. SHBG was also strongly associated with the waist to hip girth ratio (WHR). Adjustment for WHR eliminated the significant associations of SHBG with triglycerides, HDL2 mass, and apolipoprotein A-I. SHBG levels and WHR may reflect tissue sensitivity and the impact of exposure to fluctuating levels of sex hormones for a period of days, or longer. These variables may provide more insight into the role of sex hormones in lipoprotein metabolism than do single samples of circulating hormones. It is also suggested that long term effects of sex hormones on adipose tissue distribution may at least partially underlie sex-related differences in lipoprotein metabolism.

    View details for Web of Science ID A1987G463100014

    View details for PubMedID 3818901

  • GENITAL RESPONSES IN NONCOPULATORS AND RATS WITH LESIONS IN THE MEDIAL PREOPTIC AREA OR MIDTHORACIC SPINAL-CORD PHYSIOLOGY & BEHAVIOR Stefanick, M. L., DAVIDSON, J. M. 1987; 41 (5): 439-444

    Abstract

    To determine whether genital dysfunction participates in the sexual inactivity of noncopulator and MPOA-lesioned rats, penile reflexes and spontaneous seminal emission (SSE) were investigated in such animals. The display of penile reflexes was either the same or enhanced in these animals, relative to controls. Noncopulators and MPOA-lesioned rats also did not differ from controls in SSE. Plasma testosterone levels showed no differences between noncopulators and sexually active controls but tended to be elevated in rats bearing MPOA lesions. Finally, SSE did not differ between rats with midthoracic spinal cord transections and controls, suggesting that SSE is not under supraspinal inhibition.

    View details for Web of Science ID A1987K989300008

    View details for PubMedID 3432397

  • REPRODUCTIVE PHYSIOLOGY AND BEHAVIOR IN THE MALE-RAT FOLLOWING ACUTE AND CHRONIC PERIPHERAL ADRENERGIC DEPLETION BY GUANETHIDINE PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR Stefanick, M. L., Smith, E. R., SZUMOWSKI, D. A., DAVIDSON, J. M. 1985; 23 (1): 55-63

    Abstract

    The effect of guanethidine, an adrenergic neuron blocking agent, on sexual behavior, penile reflexes, and spontaneous seminal emission (SSE) in the rat was studied by acute (i.e., 4 hours prior to testing) and daily IP injection of a low (5 mg/kg) and moderately high (25 mg/kg) dose of the drug. Acute low dose treatment eliminated the expulsion of a seminal plug with behavioral ejaculation without affecting sexual behavior; while acute high dose administration significantly decreased the number of intromissions preceding ejaculation and eliminated emission in copula and SSE for 3 days, with no evidence of retrograde ejaculation. Acute high dose treatment also increased the number of long flips displayed in the penile reflex test, and resulted in significant depression in plasma testosterone (T) and luteinizing hormone (LH) levels. Daily injection with the low dose eliminated emission in and ex copula for 4 weeks, without altering sexual behavior or penile reflexes. Seminal emission in copula reappeared more rapidly after stopping injections than SSE. Chronic high dose treatment was also without effect on copulatory activity. There was a partial recovery of emission in copula by the fourth week of treatment, suggesting that a nonadrenergic mechanism had assumed this function. In penile reflex tests conducted after 4 and 8 weeks, significantly fewer erections were displayed by drug-treated animals. During the period of initial recovery of emission in copula, emission during the reflex test was markedly increased, but SSE was decreased. Plasma T was significantly suppressed after two and four weeks of daily injections, but not thereafter, while plasma LH levels were not affected by the drug.

    View details for Web of Science ID A1985ANQ1800011

    View details for PubMedID 4034620

  • THE CIRCADIAN PATTERNS OF SPONTANEOUS SEMINAL EMISSION, SEXUAL-ACTIVITY AND PENILE REFLEXES IN THE RAT PHYSIOLOGY & BEHAVIOR Stefanick, M. L. 1983; 31 (6): 737-743

    Abstract

    Spontaneous seminal emission (SSE) by sexually naive and experienced rats occurred almost exclusively in the light period of a 14:10 LD cycle. The circadian pattern of SSE slowly shifted following an LD reversal and was completely reversed by three weeks. The diurnal variation in parameters of sexual activity which are associated with sexual arousal shifted much more readily such that it was reversed within one week of the LD reversal. In contract, parameters of sexual behavior which are associated with the ejaculatory mechanism were altered following the LD shift with a phase-shifting pattern more similar to that exhibited for SSE, such that the diurnal variation seen before the LD shift was not reestablished until the third week after the shift. The characteristic pattern of SSE in 14:10 LD lighting was disrupted with two weeks of a shift to constant illumination, but the number and weight of spontaneously produced plugs did not change. Finally, there were no differences in any component of the display of penile reflexes by 29 rats tested in the dark period compared to 19 rats tested in the light period, despite significant circadian variation in the copulatory activity of these animals.

    View details for Web of Science ID A1983RS83800001

    View details for PubMedID 6665062

  • PENILE REFLEXES IN INTACT RATS FOLLOWING ANESTHETIZATION OF THE PENIS AND EJACULATION PHYSIOLOGY & BEHAVIOR Stefanick, M. L., Smith, E. R., DAVIDSON, J. M. 1983; 31 (1): 63-65

    Abstract

    Application of the topical anesthetic pontocaine (tetracaine hydrochloride) to the penis and preputial sheath virtually abolished the display of penile reflexes by intact rats. When pontocaine was applied immediately following ejaculation in copula, however, normal genital reflexes were observed in the majority of rats, albeit with a prolonged latency to the first erection relative to the control test. These same animals were, nonetheless, unable to achieve intromission when returned to the mating arena despite repeated mounting attempts. These data suggest that sensory input to the genitalia is generally necessary for the display of penile reflexes in the rat. However, stimuli associated with copulation can override the suppressive effect of sensory loss of these reflexes, presumably due to removal of supraspinal inhibition.

    View details for Web of Science ID A1983RB04000009

    View details for PubMedID 6634978

  • FURTHER-STUDIES ON ALTERATIONS IN MALE-RAT COPULATORY-BEHAVIOR INDUCED BY THE DOPAMINE-RECEPTOR AGONIST RDS-127 PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR Clark, J. T., Stefanick, M. L., Smith, E. R., DAVIDSON, J. M. 1983; 19 (5): 781-786

    Abstract

    Pharmacologic dopamine receptor stimulation by RDS-127 (2-N,N-di-n-propylamino-4,7-dimethoxyindane) resulted in qualitatively different changes in the mating pattern depending on the dose administered and time elapsed between treatment and behavioral observation. A low dose (0.25 mg/kg) selectively increased the latency to ejaculation whereas a high dose (3.0 mg/kg) decreased ejaculation latency and intromission frequency (both indicators of ejaculatory efficiency) when behavioral observations were begun 30 minutes after intraperitoneal administration. Intermediate doses (0.5, 1.0, and 2.0 mg/kg) did not alter the time required to achieve ejaculation but did lower the number of intromissions preceding ejaculation. These dose-dependent actions resemble the effects of dopaminomimetics (reported by others) on locomotor activity. When mating tests were conducted shortly (less than five minutes) after drug administration, the induction of ejaculation by the high dose was enhanced. At this time, as well as after a prolonged delay (two hours), signs of decreased arousal (longer intromission latencies) were also observed. However, the postejaculatory refractory period was altered in a time-dependent fashion, viz: it was shortened closest to the injection time, not altered 30 minutes after treatment, and increased two hours after RDS-127 administration. Finally, RDS-127 induced seminal emission (ex copula) in 2.9 +/- 0.9 (S.E.) minutes, and these emissions did not differ in weight from normal spontaneous (diurnal) seminal emissions. The RDS-127-induced seminal emission was not followed by a refractory period of similar magnitude to that seen after ejaculation in copula. The data are interpreted in terms of the involvement of dopamine receptor subtypes in the modulation of masculine sexual behavior.

    View details for Web of Science ID A1983RQ84000010

    View details for PubMedID 6647512

  • SEXUAL EXPERIENCE AND PLASMA TESTOSTERONE LEVELS IN MALE VETERANS AFTER SPINAL-CORD INJURY ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION Phelps, G., Brown, M., Chen, J., Dunn, M., Lloyd, E., Stefanick, M. L., DAVIDSON, J. M., Perkash, I. 1983; 64 (2): 47-52

    Abstract

    Fifty men with spinal cord injuries (SCI) were asked to complete a questionnaire concerning their sexuality before and after injury. Medical examination confirmed the location and completeness of the injury and extracted information about genitourologic status. The respondents rated sexuality highly as a concern in living, and a wide variety of sexual techniques were reported. A marked decrease in sexual activity, satisfaction, and feelings of sexual adequacy was reported after injury, as compared to retrospective "before injury" responses, lack of opportunity being reported as causative by 66% of the subjects and insufficient personal satisfaction by 59%. Seventy-five percent of the subjects experienced sexual arousal from genital stimulation, and several methods of eliciting erection were cited. Orgasm was described by a variety of terms. Significant differences were found between quadriplegic and paraplegic patients in answers to several items, though there was generally no difference between cervical and thoracic groups, which were more specifically broken down with respect to motor or sensory/complete or incomplete lesions. Plasma testosterone levels were found to fall well within the normal adult male range, as were levels of free testosterone and serum sex binding protein. The resulting information demonstrated more sexual concern among men with SCI than the literature previously indicated.

    View details for Web of Science ID A1983QB70600001

    View details for PubMedID 6681699

  • EFFECTS OF A NOVEL DOPAMINE-RECEPTOR AGONIST RDS-127 (2-N,N-DI-N-PROPYLAMINO-4,7-DIMETHOXYINDANE), ON HORMONE LEVELS AND SEXUAL-BEHAVIOR IN THE MALE-RAT PHYSIOLOGY & BEHAVIOR Clark, J. T., Smith, E. R., Stefanick, M. L., Arneric, S. P., Long, J. P., DAVIDSON, J. M. 1982; 29 (1): 1-6

    Abstract

    Selective changes in the mating pattern occurred 30 minutes following administration of RDS-127 (3.0 mg/kg, IP) to sexually experienced adult male rats. Marked decreases in intromission frequency and ejaculation latency were observed. These data indicate a potent effect upon conummatory mechanisms underlying copulatory behavior. The lack of effect upon arousal state was further demonstrated utilizing a "mounting test" (in which the penis is anesthetized by topical application of tetracaine hydrochloride). No difference in mounting behavior was seen. Seminal plugs were noted in a large percentage of treated animals at the time of anesthetic application. Additionally, a six-fold decrease in plasma prolactin and a lesser decrement in plasma luteinizing hormone were evident. Finally, in sexually experienced castrate animals, RDS-127 induced mounting in two thirds and intromissive and ejaculatory patterns in one third of the treated animals, 35 days postcastration. These effects were greatly attenuated by 56 days postcastration. The selective alteration of consummatory mechanisms, with little or no effect upon arousal status, suggests a neurochemical separation of these two components in the intact male rat.

    View details for Web of Science ID A1982NX40200001

    View details for PubMedID 7122715

  • EFFECTS OF A POTENT DOPAMINE RECEPTOR AGONIST, RDS-127, ON PENILE REFLEXES AND SEMINAL EMISSION IN INTACT AND SPINALLY TRANSECTED RATS PHYSIOLOGY & BEHAVIOR Stefanick, M. L., Smith, E. R., Clark, J. T., DAVIDSON, J. M. 1982; 29 (6): 973-978

    Abstract

    Administration of RDS-127 (3.0 mg/kg) induced seminal emission within three minutes of IP injection and suppressed the display of penile reflexes in intact and spinally transected rats. In Experiment 1, RDS-127 was administered to intact, sexually experienced rats in a protocol previously demonstrated to selectively lower the ejaculatory threshold of copulating animals. The incidence of seminal emission was significantly elevated by RDS-127 but penile reflexes were present in only 8% of the drug-treated rats, compared to 59% of controls. In Experiment 2, seminal emission was induced 2.3 +/- 0.4 (S.E.) minutes from injection of RDS-127. Animals which responded to RDS-127 with multiple emissions had significantly lower ejaculation latencies during copulatory tests conducted prior to drug treatment than animals which had no or only single seminal emissions following RDS-127 injection. Spontaneous seminal emission in the 3 day period initiated 2 hours after RDS-127 injection was unaffected by the drug. Spontaneously produced plugs were approximately twice the weight of those induced by RDS-127. In Experiment 3, seminal emission was induced in spinally transected rats 1.7 +/- 0.4 minutes following RDS-127 administration, whereas drug treatment attenuated the enhancement of penile reflexes observed following midthoracic spinal transection. These experiments suggest that a spinally-mediated dopaminergic mechanism is capable of stimulating seminal emission acutely in the rat and inhibiting the display of penile reflexes by the supine animal.

    View details for Web of Science ID A1982PS53000001

    View details for PubMedID 7163401

  • ROLE OF ANDROGEN IN SEXUAL REFLEXES OF MALE RAT PHYSIOLOGY & BEHAVIOR DAVIDSON, J. M., Stefanick, M. L., Sachs, B. D., Smith, E. R. 1978; 21 (2): 141-146

    View details for Web of Science ID A1978FN17000001

    View details for PubMedID 693640

Conference Proceedings


  • Estrogen plus progestin (E plus P) and breast cancer incidence and mortality Chlebowski, R. T., Anderson, G. L., Kuller, L. H., Aragaki, A. K., Manson, J. E., Stefanick, M. L., Johnson, K., Gass, M., Lane, D. S., Ockene, J., Sarto, G., Wactawski-Wende, J., Rajkovic, A., Prentice, R. L. AMER SOC CLINICAL ONCOLOGY. 2012
  • EFFECTS OF POSTMENOPAUSAL HORMONE THERAPY ON INCIDENT ATRIAL FIBRILLATION: THE WOMEN'S HEALTH INITIATIVE RANDOMIZED CONTROLLED TRIALS Perez, M. V., Wang, P., Larson, J., Virnig, B. A., Cochrane, B., Curb, D., Klein, L., Manson, J., Martin, L., Robinson, J., Wassertheil-Smoller, S., Stefanick, M. ELSEVIER SCIENCE INC. 2012: E661-E661
  • SELF-REPORTED SNORING AND CARDIOVASCULAR OUTCOMES AMONG POSTMENOPAUSAL WOMEN: THE WOMEN'S HEALTH INITIATIVE (WHI) Sands, M., Loucks, E. B., Lu, B., Stefanick, M. L., Ockene, J. K., Shah, N., Hairston, K. G., Limacher, M., Hale, L., Eaton, C. B. AMER ACAD SLEEP MEDICINE. 2012: A410-A410
  • Estrogen Alone and Lung Cancer in Postmenopausal Women Chlebowski, R., Anderson, G., Manson, J., Schwartz, A., Wakelee, H., Gass, M., Rodabough, R., Johnson, K., Wactawski-Wende, J., Stefanick, M. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2010: 394-394
  • Independent Clinical Correlates of Atrial Fibrillation in Postmenopausal Women: The Women's Health Initiative Observational Study Perez, M., Wang, P. J., Klein, L., Connelly, S., Larson, J., Limacher, M., Manson, J., Martin, L. W., Prineas, R., Rodriguez, B. L., Smoller, S., Soliman, E., Stefanick, M. L. LIPPINCOTT WILLIAMS & WILKINS. 2009: S520-S520
  • Effects of Postmenopausal Hormone Therapy on Atrial Fibrillation: The Women's Health Initiative Randomized Controlled Trials Perez, M., Wang, P. J., Cochrane, B., Curb, J. D., Klein, L., Larson, J., Manson, J., Martin, L. W., Robinson, J., Wassertheil-Smoller, S., Stefanick, M. LIPPINCOTT WILLIAMS & WILKINS. 2009: S519-S519
  • Non-small cell lung cancer and estrogen plus progestin use in postmenopausal women in the Women's Health Initiative randomized clinical trial Chlebowski, R. T., Schwartz, A., Wakelee, H., Anderson, G. L., Stefanick, M. L., Manson, J. E., Chien, J. W., Chen, C., Wactawski-Wende, J., Gass, M. AMER SOC CLINICAL ONCOLOGY. 2009
  • Non-small cell lung cancer and estrogen plus progestin use in postmenopausal women in the Women's Health Initiative randomized clinical trial Chlebowski, R. T., Schwartz, A., Wakelee, H., Anderson, G. L., Stefanick, M. L., Manson, J. E., Chien, J. W., Chen, C., Wactawski-Wende, J., Gass, M. AMER SOC CLINICAL ONCOLOGY. 2009
  • Breast cancer after stopping estrogen plus progestin in postmenopausal women in the women's health initiative. Chlebowski, R. T., Kuller, L., Anderson, G., Mason, J. A., Schenken, R., Rajkovic, A., Stefanick, M., Sarto, G., Ravdin, P., Prentice, R. AMER ASSOC CANCER RESEARCH. 2009: 78S-79S
  • Sax Differences In Peripheral Arterial Disease Rafie, A. H., Sims, T., Edwards, K. A., Phan, T., Stefanick, M. L., Assimes, T., Trammel, J. A., Olin, J., Cooke, J. P. LIPPINCOTT WILLIAMS & WILKINS. 2008: S811-S811
  • Grip strength predicts dementia in 75 to 80 year-old women: The Women's Health Initiative Memory Study (WHIMS) Atkinson, H. H., Williamson, J. D., Rapp, S. R., Lovato, J., Sink, K. M., Absher, J. R., Gass, M., Henderson, V., Johnson, K. C., Kostis, J. B., Mouton, C., Ockene, J. K., Stefanick, M. L., Lane, D. S., Espeland, M. A. WILEY-BLACKWELL. 2008: S107-S107
  • Objective measures of sleep duration and obesity in older men and women Stone, K., Blackwell, T., Ancoli-Israel, S., Ensrud, K., Stefanick, M., Orwoll, E., Cauley, J., Lewis, C., Redline, S. AMER ACAD SLEEP MEDICINE. 2007: A106-A107
  • The relationship of actigraphic sleep characteristics and measures of cognition: The mros sleep study Blackwell, T., Yaffe, K., Redline, S., Ancoli-Israel, S., Ensrud, K., Stefanick, M., Stone, K. AMER ACAD SLEEP MEDICINE. 2007: A111-A111
  • The relationship of sleep disordered breathing and cognition: The mros sleep study Stone, K., Blackwell, T., Yaffe, K., Ancoli-Israel, S., Ensrud, K., Stefanick, M., Redline, S. AMER ACAD SLEEP MEDICINE. 2007: A105-A105
  • Does calcium supplementation increase cardiovascular risk: The women's health initiative randomized trial Hsia, J., Heiss, G., Ren, H., Trevisan, M., Greenland, P., Johnson, K., Allison, M., Stefanick, M., Manson, J., Heckbert, S., Dolan, N., Sidney, S., Permanente, K. LIPPINCOTT WILLIAMS & WILKINS. 2006: 884-884
  • Risk factors for hip fracture, WHI. Robbins, J., Agaki, A., Kooperberg, C., Cauley, J. A., Chen, Z., Wactawski-Wende, J., LeBoff, M. S., Lewis, C. E., Jackson, R., Watts, N. B., Stefanick, M. WILEY-BLACKWELL. 2006: S55-S55
  • Incident mortality, cardiac and vascular outcomes among extremely obese US women: A growing health threat McTigue, K. M., Valoski, A., Chang, Y. F., Burke, G. L., Lewis, C. E., Kotchen, J., Stefanick, M. L., Van Horn, L., Kuller, L. H. LIPPINCOTT WILLIAMS & WILKINS. 2005: E204-E204
  • Sex steroid hormones in older men: Cross-sectional and longitudinal associations with bone mineral density (BMD). The osteoporotic fracture in men study (MrOS). Cauley, J., Taylor, B., Fink, H., Ensrud, K., Bauer, D., Barrett-Connor, E., Marshall, L., Nevitt, M., Stefanick, M., Orwoll, E. WILEY-BLACKWELL. 2004: S16-S16
  • Association between reported alcohol intake and changes in cognition: The Women's Health Initiative Memory Study (WHIMS) Coker, L., Rapp, S., Stefanick, M., Masaki, K., Ockene, J., Espeland, M., Langer, R., Gu, L., Shumaker, S. OXFORD UNIV PRESS INC. 2004: 82-83
  • Postmenopausal hormone therapy and body composition - Results from the Women's Health Initiative E+P trial. Chen, Z., Bassford, T., Green, S. B., LeBoff, M., Margolis, K. L., Lacroix, A., Jackson, R. D., Cauley, J., Stefanick, M. L. WILEY-BLACKWELL. 2004: S40-S40
  • Physical activity for preventing and treating obesity-related dyslipoproteinemias Stefanick, M. L. LIPPINCOTT WILLIAMS & WILKINS. 1999: S609-S618

    Abstract

    The clinical trial data were reviewed on effects of physical activity on obesity-related dyslipoproteinemias (specifically low HDL-cholesterol (HDL-C), elevated triglycerides (TG), and high total and LDL-cholesterol (TC and LDL-C)) in adult men and women.Effort was made to identify all randomized clinical trials (RCT), with exercise intervention programs of at least 4 months' duration, which had lipoprotein outcomes. Those that had both an exercise only intervention and control groups or both a diet plus exercise and identical diet only intervention groups were reviewed. Tables were developed of baseline characteristics and weight and lipoprotein changes for aerobic exercise trials by body mass index: 1) < 25.0 kg x m(-2), 2) 25.0-29.9 kg x m(2), and 3) > or = 30.0 kg x m(-2)and for studies involving resistance exercise or increased energy expenditure from daily activities versus structured exercise programs.Very few RCT were found that specifically addressed the role of physical activity in preventing or treating obesity-related adverse lipoprotein levels. There was essentially no evidence found in lean or overweight men or women to support a specific role for exercise in improving undesirable lipoprotein levels; however, trial data strongly suggest that the addition of exercise to a hypocaloric, reduced-fat diet improves HDL-C and TG in men and women with generally desirable initial levels and reduces LDL-C in men and women with initially elevated LDL-C levels. The evidence is also reasonably strong that weight loss, including that achieved solely by exercise, improves HDL-C and TG in obese men, without reducing LDL-C, whereas it remains weak for women. There are also virtually no trial data to support a role for resistance exercise or an increase in daily living activities for improving obesity-related lipoproteins.Current evidence from RCT is too limited to determine whether physical activity can raise low HDL-C or lower high TG or LDL-C levels in overweight and obese individuals.

    View details for Web of Science ID 000083756700020

    View details for PubMedID 10593536

  • RELATIONSHIP BETWEEN PLASMA LIPOPROTEINS (LP) AND SEX-HORMONES IN MEN BEFORE AND AFTER EXERCISE TRAINING Stefanick, M. L., Williams, P. T., DAVIDSON, J. M., Krauss, R. M., Wood, P. D. FEDERATION AMER SOC EXP BIOL. 1985: 847-847

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