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Symposium on effects of sex chromosomes

- By Bruce Goldman

Marcia Stefanick

Marcia Stefanick

Sex differences shape medical outcomes, and they may shape cures, too. That theme resonated throughout a June 11 campus research symposium discussing the biological and environmental causes and medical consequences of sex differences.

About 100 people attended the all-day event, titled “Beyond X and Y: The basic and translational science of sex differences,” co-hosted by Women’s Health at Stanford and the Stanford Cardiovascular Institute and held in the Arrillaga Alumni Center. The symposium featured high-profile speakers from other universities as well as from the Stanford Cancer Center, WHS and all four of the medical school’s Institutes of Medicine. “This is the first time all the Stanford institutes of medicine have pulled together, along with the WHI and SCC, to create a program,” said symposium chair Marcia Stefanick, PhD, professor of medicine.

The majority of clinical studies have involved male subjects, observed Arthur Arnold, PhD, professor of integrative biology and physiology at UCLA. But findings that apply to males don’t necessarily translate perfectly to women, he noted. The preponderance of evidence leaves little doubt that there are significant male-female differences at the cellular level in many organs of the body.

Marianne Legato, MD, professor of clinical medicine at Columbia University, pointed out that this failure to consider sex differences in studies of disease shorts men as well as women. Men appear in many respects to be at a medical disadvantage to women — for example, their shorter life expectancies and earlier vulnerability to cardiovascular disease, said Legato, the author of a textbook on this subject, as well as of two popular books: Why Men Die First and Why Men Always Forget and Women Always Remember. “We need to focus a gender-specific lens on males so that we can better understand their greater vulnerability compared with women,” she said.

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Lawrence Steinman

Men and women stand to gain from an approach that, as Arnold put it, “separates medical information into two columns.” To the extent that men and women are differentially prone to a disease, it makes sense to identify factors that protect one sex relative to the other, and then try to develop therapies that target those factors, he said. Such therapies might protect both sexes.

While men develop cardiovascular disease earlier and are more likely to be diagnosed with autism, women have higher risks of several autoimmune diseases. They are three times as likely as men to get rheumatoid arthritis or multiple sclerosis, and nine times as likely to get lupus. Why? Interestingly, said Eliza Chakravarty, MD, assistant professor of immunology & rheumatology, pregnancy tends to exacerbate lupus but ameliorate rheumatoid arthritis, suggesting that levels of female hormones play an important role, albeit with opposite effects on the two diseases.

Three times as many women as men get multiple sclerosis, said Lawrence Steinman, MD, the George A. Zimmerman Professor of Neurology and Neurological Sciences. Yet this 3-to-1 ratio has not remained constant over history, he said. Rather, the ratio has risen steadily over the last 100 years, from about 1.9 to about 3.2 now, he said. At the same time, menarche — the onset of full hormonal output in the ovaries — has been occurring earlier in women in developed countries. “We’re getting bigger and fatter,” he said, presumably due to improved public health and increased caloric intake but perhaps with unanticipated consequences.

Some other differences highlighted during the symposium: Men tend to recover from surgery more thoroughly and more rapidly than women do, but nonsmoking women were more susceptible than nonsmoking men to lung cancer and, in addition, are two to four times as likely to get pulmonary hypertension, an uncommon but deadly condition characterized by high blood pressure in the lungs.

Various speakers presented evidence that male/female differences are not entirely due to differences in the type of sex hormones produced in the gonads. Some of those differences reside in other features of the X and Y chromosomes that are found in each male cell or, in female cells, the two X chromosomes. Thus a single cell that is in all other respects identical may have characteristics that differ depending on whether it is an XX or an XY cell. Stem cell researcher and lunch speaker Renee Reijo Pera, PhD, professor of obstetrics & gynecology suggested this could hold implications for regenerative medicine, a treatment approach involving the implantation of tissues or cells generated from stem cells to correct a deficiency or regenerate an organ. “Might it matter,” she asked, “if those donor cells came from a man or a woman?”

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2022 ISSUE 1

Understanding the world within us

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