IT IS SEPTEMBER 4, 1991. Researchers from academic centers across the country are gathered at the Hunt Valley Conference Center in Maryland. To an observer, the event looks like any other professional conference. However, it is anything but ordinary. It is the start of a new frontier in health research. The scientists hail from different fields of study, yet all are devoted to studying women’s health. Invited by the newly established Office of Research on Women’s Health within the National Institutes of Health (NIH), they are tasked with setting a research agenda to address the troubling gaps in scientific information on the health of women. It is a pivotal moment in the history of science and medicine. Over the previous 40 years, the United States had made a dramatic investment in scientific research. The NIH had grown to become the world’s greatest single funder of biomedical research and set the standard for the direction and design of future research. There was, however, a glaring omission: NIH policies did not require the inclusion of women in clinical studies. At the time, researchers believed that women’s hormone cycles could complicate study results. It was also thought that women needed to be protected from any possible risk involved in scientific inquiry—despite safeguards dictated by protocols. As a result, women were generally excluded as research participants, and that’s why the Hunt Valley gathering was so important. These scientists were poised to change the standard of research, leading to federal legislation in 1993 that required women to be included in all future clinical research funded by the NIH. Breaking down barriers That 1991 gathering was a galvanizing moment for Carolyn M. Mazure, PhD, Norma Weinberg Spungen and Joan Lebson Bildner Professor in Women’s Health Research and professor of psychiatry and psychology. It reinforced her commitment to women’s health research as a scientific field of inquiry. For nearly a decade, Mazure collaborated with the NIH Office of Research on Women’s Health to advance the message that women’s health had to be studied at the national level. A turning point came in 1998, when Mazure secured a grant from The Patrick and Catherine Weldon Donaghue Medical Research Foundation and the support of Yale School of Medicine to create Women’s Health Research at Yale (WHRY), one of the first research centers in the country devoted to studying a wide array of conditions that affected women. Now, as the center celebrates its 25th anniversary, that focus has expanded to include research on the influence of biological sex and the social construct of gender on health, as well as the evolving ways in which people identify their genders. After years of excluding women from research, there was an enormous knowledge gap regarding disorders of high morbidity and mortality that affect women. Yet even after eventually acknowledging that women should be included, researchers were stuck. They could not obtain funds from granting institutions, including the NIH, without feasibility data to show how a proposed investigation might advance women’s health. “Our WHRY Pilot Project Program was designed to generate these feasibility data and broaden the scope of conditions studied in women,” said Mazure. “This research almost immediately reaped practical benefit for women’s lives in both the short and long term.” Broadening the scope of research With research that focuses on conditions ranging from cardiovascular disease to various cancers, WHRY now supports laboratory and clinical investigations that bring interventions to medical settings and the wider community. Through WHRY Pilot Project grants, Yale faculty have made innovative discoveries and provided new health information to improve the lives of women and girls. To highlight just a few of more than 100 WHRY pilot studies: investigators have developed better diagnostics for identifying heart attack in women; uncovered a lupus antibody that has been developed into a therapy and will soon be tested in clinical trials to fight breast and ovarian cancer; expanded the use of an effective therapy for autism spectrum disorder to benefit girls; and identified a culturally sensitive therapy that can be used remotely to treat insomnia in Black women. At the beginning of the COVID-19 pandemic, WHRY also fast-tracked studies investigating sex differences in the immune response to the novel virus and resilience in frontline health care providers that yielded meaningful data on both women and men. While advancing human health, the WHRY Pilot Project Program has also fostered the careers of Yale researchers. Nearly three-quarters of the funded researchers have been junior or mid-level faculty who needed initial funding to launch their research, and 60% of funded researchers are women. All WHRY researchers are supported before, during, and after their grant periods. WHRY also has served as a scientific home for NIH center grants focused on women’s health and on sex and gender differences, while also forging interdisciplinary collaborations among scientists to help answer complex questions. One such partnership brought together scientists whose expertise in neuroscience and biostatistics allowed them to better understand the genetic risk associated with Alzheimer’s disease in women. As a result of this novel team’s work, its members secured new NIH funding. Collectively, WHRY’s pilot studies have generated more than $115 million in subsequent grants to Yale faculty to further their investigations. Of this total, 86% are funded by the NIH, which is three times the success rate for new investigator-initiated NIH applications. Spreading the word Along with developing new research findings, the center began engaging the wider community from the very beginning. “Researchers were largely focusing their time and efforts on their programs of investigation, but thanks to the forward thinking of the Donaghue Foundation trustee Raymond Andrews, WHRY began sharing its findings with local and national audiences in a new way,” said Mazure. Today, the center’s outreach includes a quarterly newsletter, an informative website, and a social media presence, as well as local, national, and international presentations, and webinars. These efforts, among others, are guided by a community council of advisors, strengthening the connection between WHRY’s work and those who can benefit most. The center and its director are also active in the national conversation on women’s health, advocating for greater understanding of the ways in which the experience of gender influences health. Along with that, WHRY’s work strives to ensure that the past and current cultural norms that reduce women’s health equity are addressed. A vision for the future Just as the creation of WHRY forged new paths into scientific inquiry, that guiding principle will continue in the future. The center came into being “before an understanding of how sex and gender relate to health and well-being became a significant focus of many major institutions,” said Marc Potenza, MD, PhD, Albert E. Kent Professor of Psychiatry and the director of WHRY’s Women and Addictive Disorders Core. “Dr. Carolyn Mazure recognized the need to research these topics and translate the data into practical benefit. Her visionary program has made substantial contributions to the health of women and girls across the globe.” Now, the needs—and opportunities—have expanded. In addition to its many areas of ongoing research, WHRY has also become a leader in the developing area of study that examines the influence of biological sex and the social construct of gender on health. Here, the center seeks to include data regarding these influences, along with other key findings on the health of women into the YSM curriculum to help inform the patient care and research of future physicians and physician-scientists. Recognizing the value of a scholarly home for learning, WHRY also offers research fellowships to Yale undergraduates to foster their interest in this field. As knowledge increases, new directions of study will undoubtedly be uncovered, and the work of WHRY will continue—a fitting testament to those at the Hunt Valley conference who first sounded the alarm on the need for women’s health research. After founding WHRY 25 years ago, Mazure now plans to write and teach about the value of studying diverse populations of women; the effects of sex and gender on human health; and how human biology and social experience intersect to determine human health.