When Women’s Health Research at Yale (WHRY) was organized 20 years ago, women were not regularly studied and there was limited understanding of how sex and gender differences affected health outcomes. That’s changed in a big way.

Playing to Yale’s research strengths, WHRY has launched over 90 studies on women’s health in areas as diverse as cardiovascular disease, cancers, osteoporosis, reproductive health, autism, obesity, addictive behaviors, and intimate partner violence.

Now heading into its third decade, this self-supporting center remains at the national forefront of initiating research on women’s health and uncovering sex and gender differences that affect health outcomes.

“WHRY’s Pilot Project Program offers researchers the opportunity to explore vital questions that would otherwise not receive funding,” says Akiko Iwasaki, PhD, Waldemar Von Zedwitz Professor of Immunobiology and Molecular, Cellular and Developmental Biology. “If you don’t invest in this type of early stage research, you won’t have any breakthroughs.”

Since its inception, WHRY has provided $5 million in “seed” grants, resulting in $95 million of new external grants. Funds go directly to faculty to continue the research, a key element of WHRY’s long-range plan to integrate the study of women’s health and sex/gender differences into the fabric of research at YSM.

“These funded investigations are not ‘one-off’ studies,” says Carolyn M. Mazure, PhD, Norma Weinberg Spungen and Joan Lebson Bildner Professor in Women’s Health Research and professor of psychiatry and of psychology. “They are part of a program of research in an important area that has now shifted its attention to better understand the influence of sex and gender on how diseases and conditions develop, present symptoms, and respond to treatment.”

Of those funded, 55 percent are women, 72 percent have been junior or mid-level faculty, and 62 percent received external funding to continue their work.

Important science

Both basic science and clinical science are important to WHRY in advancing women’s health.

“Innovative laboratory studies provide essential models for how we can understand health and disease biology,” Mazure says. “They provide the necessary foundation for subsequent studies on humans.”

For example, recently in Science, Martin Kriegel, MD, reported on lab work that directly evolved from his WHRY-funded project as an assistant professor of immunobiology. He showed that bacteria in the small intestines of mice and humans can travel to other organs and trigger an autoimmune response that can be suppressed by targeting the bacteria. Such findings provide new approaches for treating autoimmune conditions, such as systemic lupus, which occur at far greater rates in women.

Clinical investigations funded by WHRY often have immediate practical application, such as work by Pamela Ventola, PhD, assistant professor in the Child Study Center, showing the efficacy of a treatment for girls with autism spectrum disorder. Previously, the social-interaction behavior therapy had been tested only with boys.

In one of WHRY’s earliest studies, Peter Salovey, PhD, Chris Argyris Professor of Psychology, demonstrated the efficacy of public health messages now regularly deployed to encourage women at elevated risk for breast cancer to use routine mammography screening.

WHRY’s Pilot Project Program also fosters interdisciplinary collaborations. For example, Alessandro D. Santin, MD, of the Department of Obstetrics, Gynecology and Reproductive Sciences, is committed to developing new approaches to the treatment of ovarian cancer. Santin and W. Mark Saltzman, PhD, Goizueta Foundation Professor of Biomedical Engineering and a pioneer in the development of nanoparticles, began working together to use these ultra-tiny delivery systems that can preferentially target and bind to ovarian cancer cells and administer a potent chemotherapy agent.

Knowing our history

Although many conditions such as autoimmune disease, Alzheimer’s disease, depression, and opioid addiction affect women disproportionately or in different ways women were generally not included as participants in clinical research until the mid-1990s. It was then that the National Institutes of Health (NIH), the greatest single funder of biomedical research in the country, began requiring the inclusion of women.

“The exclusion led to a significant gap in our empirical base of knowledge on women’s health,” Mazure says. “As a result, we have not had sufficient data on the diseases and conditions that most affect women, and we have not had a clear understanding of how women and men differ in matters of their health.”

The focus on studying males is not unique to human investigation. In January of 2016, the NIH began requiring that laboratory researchers use both male and female animals and tissues and determine the sex of cells. WHRY has been funding studies in female model systems since 2000, with studies by Amy Arnsten, PhD, professor of neuroscience, on the role of gender in stress-induced cognitive dysfunction; Ronald Duman, PhD, Elizabeth Mears and House Jameson Professor of Psychiatry, on neurotrophic response to ovarian hormones; and Jane Taylor, PhD, Charles B.G. Murphy Professor of Psychiatry, on sexual dimorphism in motivation and inhibitory control.

The NIH’s new rule recognized that the differences between males and females exist even at the individual cellular level, where nuclei typically contain either XX (female) or XY (male) sex chromosomes and influence much more than hormone production: They affect how our genome is read.

New day at Yale for sex and gender research

After graduate school and three years at the NIH, Mazure received fellowship training at Yale before being invited to join the faculty. As a clinician and an NIH-funded researcher studying depression, Mazure found that stress is a more potent pathway to depression in women than men and used these findings to inform treatment interventions.

Observing how data on women’s health and sex and gender differences were lacking in other medical specialties, Mazure sought and received a grant in 1998 from The Patrick and Catherine Weldon Donaghue Medical Research Foundation to create Women’s Health Research at Yale.

WHRY’s prime directive is to develop research that has a practical benefit to women’s health and to understanding health differences between and among women and men.

In addition, WHRY shares new health findings with the community and trains the next generation of researchers through its various educational programs. The graduates have gone on to significant research positions and studying women’s health and sex/gender differences.

The way forward

While the past 20 years have led to WHRY making numerous advances in research, practice, and education, significant challenges remain. In a recent study led by Sanket Dhruva, MD, published in JAMA Internal Medicine, it was shown that medical devices are not generally evaluated for safety and effectiveness on the basis of the users’ sex, age, or race.

“The future of integrated science and medicine lies in precision,” Mazure says. “That means paying attention to sex and gender.”

Mazure knows there will always be a reason to study women and the differences between and among women and men. And she feels confident that WHRY has been built to last and lead the way.

“If we are to help people live happier, healthier, more productive lives, we can’t overlook the differences that might exist in more than half of everyone on the planet,” she says. “Now is the time to embrace and study what makes us different.”