Marcia Stefanick, PhD: A Pioneer in Women’s Health and Sex Differences Research
Marcia L. Stefanick, PhD has spent her career changing the way medicine understands both the differences and similarities in health across sex and gender. A professor of medicine at Stanford and a leading researcher in women’s health and sex differences, she has dedicated decades to advocating for the inclusion of women in clinical trials and challenging outdated medical norms. As a principal investigator in the landmark Women’s Health Initiative (WHI) and co-founder of Stanford’s Women’s Health and Sex Diversity in Medicine (WHSDM) Center, Dr. Stefanick has shaped public health policies and medical guidelines that continue to influence patient care all over the world.
“I’m interested in everything that relates to sex and gender across the life course,” says Dr. Stefanick. “My research has been very autobiographical—I first studied the menstrual cycle, then pregnancy complications, then midlife and menopause, and now aging.”
Early Life and Career Path
Born in Western Pennsylvania into a family of seven children, Dr. Stefanick developed an early curiosity about sex differences—wondering why puberty affected her brothers differently and why societal expectations varied by gender.
“I was always trying to figure out—when my brothers went through puberty, is that going to happen to me? Why do they get to do certain things, and I don’t? That made me interested in both biology and gender norms,” says Dr. Stefanick.
After spending a year in Germany as a Rotary International Exchange student, she pursued a degree in biology from the University of Pennsylvania, where she became interested in sex differences, particularly in primate behavior.
“When I graduated, I had hoped to study lowland gorillas in Africa, which led me to the Oregon Regional Primate Center. There, I became a research assistant in a sex hormone laboratory and developed a deeper interest in hormones and behavior and neuroendocrinology. This motivated me to pursue a PhD in Physiology with Julian Davidson at Stanford,” says Dr. Stefanick.
During graduate school, she realized she was not meant to be an animal researcher. Seeking a new direction, she connected with researchers at the Stanford Prevention Research Center (SPRC) who were focusing on physical activity and heart disease prevention.
Breaking Barriers in Research
At the SPRC, Dr. Stefanick’s research in the early 1990s primarily focused on body composition, weight loss, and exercise’s impact on cardiovascular risk. At the time, clinical trials were overwhelmingly conducted on men.
Her first two trials—one on exercise and HDL cholesterol and the other on diet, exercise, and weight loss—only included men because that was all that was funded. Frustrated by this, she refused to conduct another male-only study, successfully pushing for the inclusion of pre-menopausal and post-menopausal women in subsequent research.
“I told them, ‘I’m not doing another study without women. We have to include women in our research and not only study men’,” says Dr. Stefanick.
Her interest in sex and hormones led her to take on a National Institutes of Health (NIH) request for applications to study menopausal hormones and heart disease. At the time, doctors were widely prescribing menopausal hormone therapy (HT), often referred to as hormone replacement therapy (HRT), for older women despite a lack of research on its effects. Dr. Stefanick and her colleagues designed one of the first studies to examine these treatments.
This resulted in the Postmenopausal Estrogen/Progestin Interventions Trial (PEPI), published in 1995, which was the first clinical trial by the National Heart, Lung, and Blood Institute (NHLBI) conducted exclusively on women. “It was the first trial done by NHLBI that had only women in it,” says Dr. Stefanick with pride.
Women’s Health Initiative: A Landmark Study
Dr. Stefanick’s PEPI trial laid the foundation for the Women’s Health Initiative (WHI)—the largest study of women’s health ever conducted. Launched in the 1990s, WHI enrolled nearly 162,000 women at 40 clinical centers nationwide to study menopausal hormone therapy, diet and cancer risk, and calcium and vitamin D supplementation.
WHI is still ongoing, and Dr. Stefanick serves as Principal Investigator of the Western Regional Center. “It’s the biggest study of women’s health ever done—and it’s still going on,” says Dr. Stefanick.
The WHI hormone trials, published in 2002 and 2004, challenged long-held medical beliefs. Doctors were prescribing menopausal hormone therapy for older women to prevent heart disease, but the study found that HT actually increased the risk of strokes, heart attacks, breast cancer, and dementia. Within a year of publication, HT prescriptions in the US dropped from 20 million to 6 million. “Doctors became afraid to prescribe hormones for menopause management. Women now ask, ‘Why won’t anyone treat my menopause symptoms?’ There are alternative estrogen therapies that don’t carry the same risks, but they remain underutilized,” says Dr. Stefanick.
Dr. Stefanick is currently leading the largest-ever study on whether physical activity prevents heart disease—a question that, despite decades of research, has never been definitively proven.
“We’ve never actually proven that physical activity reduces heart disease. All our data is based on surrogate markers—blood pressure, cholesterol, glucose tolerance—but we haven’t studied enough men or women (or nonbinary people) to say for sure,” says Dr. Stefanick.
The WHSDM Center: Advancing Sex Differences Research
Dr. Stefanick believes that one of the biggest problems in sex differences research is the overemphasis on sex hormones while ignoring other biological factors and broader sociocultural influences. “People tend to believe it’s all about estrogen and testosterone, but the biggest biological difference is probably the X chromosome. Every cell in an XX (female) body is different from every cell in an XY (male) body and some people have other variations of X and Y combinations,” says Dr. Stefanick.
For example, women have a stronger immune response than men, yet medical studies rarely adjust for these differences. Even in vaccine development, the COVID-19 vaccine was given at the same dose to men and women, despite evidence that women may need much lower doses.
“We don’t need to treat women like men. We are not men. We need to treat women like women—XX people with estrogen between puberty and menopause and with low estrogen after menopause, which may be over a third of our lives,” says Dr. Stefanick.
To address these gaps, Dr. Stefanick co-founded the WHSDM Center at Stanford, which serves as a hub for sex and gender research in medicine. The center funds studies, ensures that departments consider sex and gender in research, and promotes the inclusion of underrepresented groups in medical studies.
“Our goal at the WHSDM Center is to encourage researchers to study sex differences at every level—cells, tissues, animals, people, and populations,” says Dr. Stefanick.
Future Research Priorities
Dr. Stefanick continues to advocate for more inclusive research in several key areas:
- Menopause and why some women have more severe symptoms than others and how to treat these more serious cases
- Adverse pregnancy outcomes and their link to increased risk of diabetes and premature heart attack
- Aging in women and why women live longer than men in many parts of the world
- LGBTQ+ health research and the need for broader representation
“Women are incredibly resilient,” says Dr. Stefanick. “Our culture doesn’t value women in the same way it values men, yet women persist. I just love women. Women are incredible.”
