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Women's Health Research Center Aims to Change How Science Views Sex Differences

March 1, 2017

Women’s Health Research at Yale helps produce better health outcomes for women and men.

For many, the phrase “women’s health” brings to mind clinical care focusing exclusively on anatomy that is uniquely female—namely, reproductive health. This seemingly easy mistake of aligning women’s health solely with reproductive health is one reason that women have historically been excluded as participants in research on conditions from which both women and men suffer, such as cardiovascular disease, cancers, and so much more.

This misconception of what constitutes women’s health has left a large knowledge gap about risk factors, signs and symptoms, and treatment and prevention strategies as they apply to women. It’s a problem that Carolyn M. Mazure, PhD, the Spungen-Bildner professor of Psychiatry and Psychology at the Yale School of Medicine, has dedicated her career to fixing.

We have to discover the underlying biological and psychosocial mechanisms of these sex differences in order to treat both women and men effectively. Carolyn M. Mazure, PhD

After obtaining research training at the National Institutes of Health and receiving her doctorate in clinical psychology, Mazure came to Yale on a clinical fellowship. Throughout her education, she was interested in sex and gender differences in health and disease and noted that “The ‘male response’ was often used as the normative response, and the ‘female response’ was seen as atypical.” As she says, “Early on, this struck me as not a very useful approach to understanding what was happening to women. And I found that in scientific studies, sex and gender differences weren’t talked about much at all.”

One of Mazure’s early research interests focused on depression. All over the world, women suffer from depression at higher rates than men. “This fact is a clue that there are different risk factors and perhaps different ways to treat and prevent depression,” she says. “Understanding that this difference occurs can lead to uncovering sex-specific underlying causes and then to better interventions for everyone.”

Or consider smoking and the difficulties in quitting, another of Mazure’s longstanding research interests. Men continue to smoke largely to satisfy a craving for the nicotine contained in cigarettes. Women tend to smoke to reduce stress and manage their weight and moods.

As a result, men using nicotine replacement such as the nicotine patch to quit have more success than women who try the patch, Mazure says. And women need other approaches to be successful in quitting.

Discovering these differences presents an enormous opportunity, she says. “And it tells us that we have to discover the underlying biological and psychosocial mechanisms of these sex differences in order to treat both women and men effectively,” Mazure says.

A research powerhouse is born

In 1998, Mazure met Raymond Andrews, who at the time was a trustee of the Patrick and Catherine Weldon Donaghue Medical Research Foundation, which provides grants “for medical research of practical benefit.” This “real meeting of minds,” as she calls it, set in motion an extraordinary effort to expand the scope of what is considered women’s health and advance biomedical research for the benefit of all by studying women and by studying sex differences.

With a goal of fostering and integrating the systematic, interdisciplinary study of women and sex differences into research, the Donaghue Foundation awarded Mazure a generous grant to build Women’s Health Research at Yale (WHRY), a center within the Yale School of Medicine.

Over the past 19 years, the center has used the Donaghue grant and other funds it has raised to initiate and support new studies on innovative ideas in the field of women’s health and to study sex and gender differences in health. To date, WHRY has granted $5 million to fund 80 pilot studies conducted by Yale faculty members, and “due to the excellence and the tremendous reach of the faculty, we have influence around the country and internationally,” Mazure says.

For innovators in need of support, those pilot grants are a springboard. It’s not possible to get grants from the National Institutes of Health (NIH), the largest single source of funds in the United States, unless you’ve conducted initial studies on a topic, Mazure says, adding that Women’s Health Research at Yale has helped Yale researchers develop preliminary data so they can apply for larger grants. This has resulted in researchers bringing over $85 million of new grants into their labs and clinical research settings—and using those grant dollars to discover crucial sex differences that affect health outcomes.

Erica Spatz, MD, a grant recipient, is developing a new approach to diagnosing and treating women who display different kinds of evidence of heart attacks. 

The intent is not just to support one study, but to spur ongoing investigation into sex and gender differences and health. “Once we introduce bright people, such as the extraordinary faculty here at Yale, to the idea that sex and gender can influence outcomes, they tend not to step back,” she says. “It’s like opening a new door to exciting and important possibilities for informing us on how to advance our health.” About half of WHRY’s pilot grants have gone for basic science project—studies carried out to discover underlying processes, such as one that uses mice to test the effectiveness of a virus in eliminating ovarian cancer cells—while the other half has gone to clinical or applied science that involves testing treatments on patients.

“Since our goal is to broaden the scope of what is considered women’s health, we fund projects on heart disease, cancer, stress and depression, autism,osteoporosis, and autoimmune diseases, to name a few,” she says.

Some of the resulting findings have changed how scientists conduct their research; others have had a practical effect on people’s lives. For example, in 2000, the center financed the first study to look at sex differences in heart bypass surgery recovery, conducted by Viola Vaccarino, MD. Women, it turns out, had worse outcomes than men, with more re-hospitalizations and infections and less social support. Cardiologists explaining risks of the surgery to women no longer had to act on the presumption that men and women have the same outcomes and could instead provide more accurate information to women contemplating the surgery and, more importantly, better aftercare to those who undergo it.

Another investigation financed by the center and conducted by Bruce G. Haffty, MD, found that the BRCA1 and BRCA2 gene mutations predict a greater risk for recurrence of breast cancer as well as the chances of getting the diseases in the first place. “This has changed how women make decisions in the face of this diagnosis,” Mazure says.

A few recently supported studies involve adolescents and children, such as one by Hilary Blumberg, MD, on how long-term stress has a more detrimental effect on the brain development of female teenagers than males, and another by Pamela Ventola, PhD, on a behavioral therapy for girls on the autism spectrum.

Expanding upward and outward

Mazure continues to develop the center as a place where “scientists can work in an integrated fashion to answer complicated questions,” she says. In addition to training the next generation of researchers to be sensitive to sex and gender differences, she seeks to ensure that legislators and key institutional leaders are informed about the importance of considering the influence of sex and gender in biomedical research—from study designs to the approval and marketing of medications.

When Mazure first envisioned the center, Andrews impressed on her the importance of involving the community and ensuring a “practical benefit” would be relayed to others. To that end, Mazure has partnered with community members to build an advisory council of both local and national community leaders, who share the center’s message with the wider public. One of the avenues for delivering information has been a recent social media campaign that includes entertaining and informative videos that share the theme that most of us “don’t know the half of it” when it comes to women’s health research, and the other half is worth knowing.

For a self-supporting research center, sustained by outside donors and grants, to flourish as long and with as wide a reach as Women’s Health Research at Yale is unusual. “My temperament is to do everything carefully, in a stepwise manner,” Mazure says. “I just build methodically and, with the help of many supporters and scientists, it keeps getting bigger.” Along with her perseverance, her passion has fueled her mission. “I really love this work,” she says. “I feel very committed to it. It gives me a lot of energy and enthusiasm, because there’s nothing quite as wonderful as discovering something that can help someone.”