Hadine Joffe

Despite making up half of the population, women have been historically underrepresented in clinical research studies. Diseases, drugs, devices and other therapeutic innovations may impact men and women differently, which is why it is crucial to consider sex and gender differences in research. The Mary Horrigan Connors Center for Women’s Health & Gender Biology at the Brigham advocates for a sex and gender lens across all medical research and works with partnering organizations to promote dialogue that advances the health of women.

Hadine Joffe, MD, MSc, is the executive director of the Connors Center. She is also the vice chair for research for the Department of Psychiatry. At the Connors Center, Joffe supports and advances new research that highlights the ways we can include and represent women in research studies. Joffe spoke with CRN and answered questions about the Connors Center’s mission, COVID-19 and sex differences, and the importance of studying women’s health.

In the news we hear about a sex and gender gap in COVID-19. Can you talk about why this is happening?

HJ: Although there are similar numbers of cases between the sexes, men are more likely to die from COVID-19 than women. There are several possible explanations: differences in lifestyle, types of care received, behavior, and biology, such as how people respond to different interventions. The immune system is key. A woman’s immune system tends to fight infection more robustly, which might help to partially explain the gap in deaths, as well as differences in cellular factors and medical comorbidities. It’s difficult to know for certain why this gap exists without doing more research because there are so many factors to consider, but it’s most likely due to a combination of reasons, both social and biological. Sometimes what we think are sex differences may actually be explained by gender differences in behavior (e.g., handwashing, mask wearing) and occupational exposures (e.g., transportation roles) as present in society.

Why is it so important to consider sex differences in research?

HJ: Oftentimes people ask why we should assume there are differences between biological men and women. A helpful comparison that I offer is that we study people with different ages because we assume there are differences between kids, adults and the elderly due to biology. That can also be the case between men and women.

The goal of our research is to discover mechanisms that explain sex differences in morbidity and mortality in conditions that affect both men and women, as well as investigating disorders specific to women. We take a lifespan perspective, looking at biological differences the lifespan. And we especially focus on periods specific to women such as child-bearing years, perimenopause and menopause. All of these are times when differences, including changes in hormones, may be most at play for women.

If we want to optimize the health of everybody, we must consider the biological differences between men and women. But we also need to look beyond the biological differences and consider the behavioral and lifestyle differences between the genders, because they also play a key role. Disparities in outcomes can be rooted in gender-segregated occupational exposures and gendered behaviors that have nothing to do with biology. Instead of only focusing on innate sex differences as drivers of female-male differences, we should examine how life experiences vary between all genders. In doing so, we better understand where research should be focused and what we can do to save more lives.

Can you talk about the Connors Center and its mission?

HJ: The Connors Center’s mission is to improve health for everybody. We take a sex and gender lens, as opposed to starting out with the assumption that there are no differences. We’re focused on women because oftentimes women may be more adversely affected, or because we don’t know enough about health in women because women haven’t been included in the prior research. The Connors Center strives to ensure optimal outcomes for both women and men.

What is the First.In.Women Precision Medicine Platform at the Connors Center?

HJ: The First.In.Women Precision Medicine Platform is one of our major pillars of research. It’s an organizational structure to advance research and educate, inform and engage a range of stakeholders, ensuring novel therapeutics for diseases affecting women are optimally understood in both women and men. First.In.Women funds and promotes research within the Brigham that studies treatments across all diseases that affect the health of women. With philanthropic support from the Women’s Health Advisory Board, the Connors Center Ignite Fund supports Brigham investigators who are igniting change in research by advancing our understanding of female-specific and sex-differentiated effects of new therapies. We also conduct educational programs and engage in conversation with academics, venture capitalists, biopharma, biotech companies, government groups and more to partner with them to advance this agenda. We work both within the Brigham and its academic community as well as externally to understand novel therapeutics and their efficacy.

What else is the Connors Center involved in?

HJ: Another major research pillar is how stress affects the health of women. We want to understand the different types of stress, such as environmental, biological or nutritional, and how it affects health and the way the brain processes that stress, particularly in aging women. This research pillar was launched with philanthropic support from the Women’s Health Advisory Board, through which Gretchen Fish funded our Women’s Health Interdisciplinary Stress Program Research (WHISPR) to stimulate science examining the impact of stress on the health of women and engage across the diverse community of stress investigators.

The Center recently received a grant from the National Institutes of Health. Can you talk about what it will be used for?

HJ: We received a U54 Center grant from the NIH that supports a 5-year, multi-project investigation into the neural processing of stress and its link to adverse health outcomes in aging women. The grant will support this research through The Brigham/Harvard Center for Stress and Neural Regulation of Reproductive Aging Health Outcomes. We have assembled a network of investigators across the Brigham and Harvard Medical School that will study the role of stress and its neural mechanisms associated with reproductive-aging health conditions in postmenopausal women that increase their risk for cardiovascular disease and dementia. Results of this investigation will improve the health of postmenopausal women.

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