discoveries magazine

Sex Matters

By “sex” I mean biologic sex, not that other kind. And by “matters,” I mean whether you are female or male makes a difference in health, disease, and patient care.

An illustration of a man and a woman sitting on pill bottles at different heights.

Illustration: Anna Parini

Ask 10 small children whether boys are different than girls and, guess what, they will all say “yes”! But many of the best-educated members of society — the physicians and medical researchers who understand the intricacies of the human body — apparently have forgotten what every child knows.

Medical researchers have paid scant attention to sex differences until very recently. Clinicians often become gender-blind in the exam room, doling out diagnoses and prescriptions in the same way for both sexes. The result is that women too often are misdiagnosed, overprescribed, or otherwise harmed by a medical system that has been designed predominantly around the male body.

The fact remains that, today, most diseases, medications, health behaviors, and health prevention strategies have not been studied in a way that helps women as much as men. Even when differences are revealed, clinicians may not be informed — or may not inform their patients.

And the differences are striking. Most drugs (80 percent) withdrawn by the Food and Drug Administration between 1997 and 2000 were removed in part because they posed greater health risks or adverse health effects in women. These medications were never even studied in women, only in men. We now know that many drugs are metabolized differently by women’s bodies, for reasons related to hormone and size differences, but we do not routinely change dosages for women. Common drugs that fall into this category are the heart medications digoxin and propranolol as well as the blood thinner warfarin.

Gender-blind exam rooms lead to women too often being “misdiagnosed, overprescribed, or otherwise harmed by a medical system that has been designed predominantly around the male body.”

One of the most important discoveries about the variations between women and men was made right here at Cedars-Sinai by Noel Bairey Merz, MD, and the team she directs at the Barbra Streisand Women’s Heart Center. They found that women experience different heart attack symptoms than men because what causes heart attacks in women is different than what causes them in men. Until that was uncovered, women experiencing heart attacks often were misdiagnosed and dismissed — some even dying unnecessarily. We also know that underlying disease often acts differently in the sexes. For example, diabetes in women infers a much higher risk of coronary heart disease than it does in men.

The National Institutes of Health (NIH) tried to implement changes to remedy these disparities in care in 1993 with the NIH Revitalization Act. It mandated that all clinical trials funded by NIH must include women and minorities (unless the research question was specific to one gender, as in prostate cancer). Yet by 2009, only 38 percent of participants in these trials were women, and only 14 percent compared women to men. Others threw women into the mix but did not bother to analyze sex differences, and some didn’t include women at all. Even a study on LDL-C cholesterol levels and cardiovascular risk published in 2016 in the Journal of the American Medical Association — the premier academic publication — was made up of only 24 percent women and, importantly, did not compare those women to men in any of the findings. The NIH also has acted to correct what it called “an over-reliance on male animals and neglect of attention to the sex of cells” in preclinical research. The sex problem is present at every level of research.

Why the reluctance to study women? One major reason is that women are complicated. The menstrual cycle means their hormones fluctuate; those on birth control may exhibit different levels than those who are not; they go through menopause — more fluctuation! — with some using hormone replacement and others not. But just because women are more complicated does not mean the medical community should accept lack of knowledge, or generalize for women from studies on men. The human organism is complex in many ways, but we do not allow this to stop us from studying the genome, or cancer, or stem cell technology.

It is time to raise awareness more broadly and insist that we include women in all appropriate clinical studies and provide sex-related results. In 2016, at Cedars-Sinai, Dr. Bairey Merz and I launched a lunch-and-learn series on gender medicine to help educate our colleagues. Topics we have covered include sex and the brain (neuro-psychiatric sex differences), sex differences in the heart, and sex differences in the emergency department. We also have begun to establish a list of Cedars-Sinai faculty who can offer expertise in sex differences related to other areas of health and disease.

The goal of gender equity in health research cannot be met by the professionals alone. I encourage every reader of this magazine to volunteer for appropriate clinical studies, ask your doctor whether your treatments affect women differently than men, and advocate for the best care for women.

About Dr. Kilpatrick

Sarah J. Kilpatrick, MD, PhD is chair of the Department of Obstetrics and Gynecology, is associate dean for faculty development, and holds the Helping Hand of Los Angeles Chair in Obstetrics and Gynecology. She is associate editor of the American Journal of Obstetrics and Gynecology and sits on the editorial board of Contemporary Obstetrics and Gynecology. Her clinical and research expertise extends to the management and outcomes of very preterm birth as well as maternal morbidity and mortality, and hypertension in pregnancy.