For much of modern medical history, clinical research relied overwhelmingly on male participants. Until the last decade of the 20th century, women were routinely excluded from clinical trials, especially in drug development, because of concerns about hormonal variability and pregnancy risk.
The result was a vast evidence gap. Because most medications, diagnostic criteria, and treatment protocols were developed mainly from data on male subjects, there was limited understanding of how women experienced disease or responded to treatment differently from men. Women were more likely to be misdiagnosed, under-treated, or prescribed drugs that hadn’t been adequately tested for their physiology.
Growing concern about the limitations and consequences of these practices prompted federal action. More than 40 years ago, the National Institutes of Health (NIH) issued a policy encouraging the inclusion of women in NIH-funded research, but compliance was uneven. By 1990, the NIH established the Office of Research on Women’s Health (ORWH) to ensure that women were meaningfully included in research. Shortly thereafter, Congress codified sex inclusion policy into law as part of the NIH Revitalization Act of 1993—mandating that NIH-funded clinical trials include women and analyze results by sex when appropriate and prohibiting cost as a justification for exclusion.
Over time, researchers recognized that differences in hormones, immune function, metabolism, cardiovascular anatomy, and brain structure significantly influence health outcomes in distinct ways in men and women. Incorporating sex as a biological variable became essential to improving scientific accuracy. What had once been treated as a secondary consideration became recognized as essential to scientific rigor and improved outcomes for men and women alike.
Yale creates a national model for women’s health research
As the national research landscape began to change, Yale School of Medicine emerged as an early leader in women’s health research.
In 1998, Carolyn M. Mazure, PhD, founded Women’s Health Research at Yale, an interdisciplinary center designed to integrate sex-based analysis into mainstream biomedical science. To formally launch its research mission, the center immediately established a Pilot Project Program and awarded approximately $1 million to 11 Yale faculty members investigating sex differences in health and disease. The program established a formal framework for supporting interdisciplinary research across Yale. In the years that followed, the center continued awarding multiple pilot grants annually to Yale researchers across a wide range of disciplines.
A pioneer in women’s health research, Mazure helped shape the national conversation around sex-informed science and policy. Beyond Yale, her work influenced federal research priorities, contributed to national policy discussions, and helped other academic medical centers develop women’s health research programs and strategies. Over the course of her career, she testified before Congress and the United Nations on issues related to women’s health and sex differences in research. In 2024, she received the Elga R. Wasserman Award in recognition of her leadership and impact advancing the careers of women in academic medicine.
Women’s Health Research at Yale was designed as an interdisciplinary incubator rather than a single-disease center. Its work focused on conditions that affect women disproportionately, such as autoimmune disease and some mental health disorders; conditions that present differently in women and men, including cardiovascular disease and cancer; and conditions unique to women, such as pregnancy and menopause.
By embedding sex-based analysis into mainstream biomedical science, Women’s Health Research at Yale helped shift the conversation from whether differences exist to how those differences can inform better care. The center’s pilot project program quickly expanded across many of the most significant health challenges affecting both women and men.
Expanding the science: Discovering meaningful biological differences
Over nearly three decades, Women’s Health Research at Yale-supported investigators helped transform understanding of how biological sex influences disease, treatment response, and long-term health outcomes. Through more than 100 pilot projects, the center supported research across many of the leading causes of illness and death—including heart disease, cancer, immune disorders, mental health conditions, and neurodegenerative disease.
Heart disease: Improving diagnosis and outcomes for women
For decades, most cardiovascular research was based largely on men, even though heart disease is the leading cause of death among women. Early Women’s Health Research at Yale pilot projects helped demonstrate that women often experience different symptoms, disease patterns, and outcomes.
One of the center’s inaugural studies, led by Viola Vaccarino, MD, PhD, showed that women experienced poorer short-term outcomes after coronary bypass surgery than men. Years later, Samit Shah, MD, PhD, advanced research into coronary microvascular disease and coronary vasospasm—conditions more common in women that may not appear on standard cardiac imaging but can still lead to serious symptoms and cardiac events.
Cancer: Linking genetics, hormones, and treatment response
As researchers began examining how genetics and sex interact in cancer, Yale investigators helped clarify important differences in risk and treatment response.
Bruce Haffty, MD, helped clarify how BRCA1 and BRCA2 mutations affect breast cancer recurrence risk, informing surveillance and preventive care strategies that are still used today. Other Yale researchers studied ovarian cancer treatments, breast cancer biomarkers, and new precision medicine approaches for cancers related to BRCA mutations.
Immune disease: Explaining why immune responses differ
The center also supported research into why immune and inflammatory diseases affect women and men differently.
Akiko Iwasaki, PhD, became internationally recognized during the COVID-19 pandemic for research examining why men experienced higher mortality rates from the disease. Her work identified key differences in immune response and inflammation that helped explain why disease severity differed between women and men.
The work helped expand understanding of how immune regulation differs between women and men—and why those differences matter across infectious disease, autoimmune conditions, and chronic inflammation.
Brain and mental health: Exploring sex-linked neurological differences
Women’s Health Research at Yale also helped advance research into psychiatric and neurological disease.
Hilary Blumberg, MD, identified sex-linked differences in adolescent bipolar disorder using brain imaging, while other Women’s Health Research at Yale investigators studied depression, addiction, stress response, and Alzheimer’s disease.
Together, these projects helped strengthen recognition that neurological and psychiatric conditions may develop and present differently in women and men.
Reproductive and lifespan health: Addressing historically understudied conditions
The center also supported research into reproductive and hormonal health conditions long understudied in biomedical research.
Yale investigators studied infertility, pregnancy-related depression, preeclampsia, endometriosis, menopause, ovarian aging, maternal infection, and postpartum health. Other projects explored osteoporosis, obesity, aging, and chronic pain, helping broaden scientific understanding of women’s health across the lifespan.
Across these areas and many others, Women’s Health Research at Yale helped establish sex-informed science as a critical part of modern biomedical research. What began as an effort to close a major evidence gap evolved into a broader movement toward more precise, personalized care for everyone.
From evidence gap to precision medicine: The next era
Women’s Health Research at Yale began during a period when women were only beginning to be systematically included in biomedical studies. The early phase focused on representation—ensuring women were studied at all. The next phase identified meaningful biological differences in how disease develops, presents, and responds to treatment.
Today, the field is increasingly focused on translating those discoveries into more precise diagnostics, treatments, and prevention strategies.
Women’s Health Research at Yale collaborates across cardiology, oncology, psychiatry, immunology, neurology, emergency medicine, and public health to examine how sex influences disease mechanisms, symptom presentation, treatment response, and long-term outcomes. Studying these differences improves care for everyone. Most major causes of death—heart disease, stroke, cancer, and mental health disorders—affect both sexes, but not identically. Understanding sex differences sharpens diagnosis, refines therapies, and improves outcomes for all.
In recent years, investment in women’s health research has grown, reflecting broader recognition that sex-informed science strengthens medical accuracy. Women’s Health Research at Yale supports pilot grants, interdisciplinary collaboration, and translational research infrastructure that bridges laboratory discovery and patient care.
Women’s Health Research at Yale also demonstrated the long-term value of strategic early-stage research investment. Between 1998 and 2025, the center invested approximately $6 million through 108 pilot projects across Yale School of Medicine and the university. Those projects later generated more than $124 million in external research funding, helping launch new scientific programs, support emerging investigators, and expand Yale’s leadership in sex-informed biomedical research.
What began as an effort to close an evidence gap has become a driver of scientific innovation. The field has moved from exclusion to inclusion, from recognizing differences to understanding their biological basis, and from discovery to more tailored treatment—advancing precision medicine for women and men alike.
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