Transforming the Health of Women Through Research

Illustration of brain in head

At Brigham and Women’s Hospital, the Mary Horrigan Connors Center for Women’s Health and Gender Biology directs a wide range of clinical and basic research programs that investigate how sex and gender differences affect women’s health and how using this lens can improve the health of both genders.

“In the past decade, there has been significant progress in women’s health research, in part due to research at the Brigham,” said Hadine Joffe, MD, MSc, executive director of the Connors Center. “However, the extent to which diseases, drugs, devices and other therapeutic innovations may impact women and men differently is still unknown for many health conditions. The Connors Center strives to change this paradigm.”

A Rich History of Improving the Health of Women

Since its founding in 2002, the Connors Center at Brigham and Women’s Hospital has focused on developing national policies that help regulatory agencies include a sex and gender lens in research in the U.S. This focus on policy has led to high-impact work, such as the development of the policy on sex as a biological variable that the National Institutes of Health (NIH) put into effect in 2016. This policy mandates that researchers use both male and female animals and cells in lab research.

“Today, the Connors Center operates from our translational research program that we call the Precision Medicine Platform (FiW),” said Dr. Joffe. “The FiW platform is an organizational structure that helps fund and promote research within the Brigham that investigates treatments across all diseases that affect the health of women. Through FiW, we also aim to educate, inform and engage a range of stakeholders, ensuring novel therapeutics for diseases affecting both genders are optimally understood in both women and men.”

Importance of Applying a Sex and Gender Lens in Research

The Connors Center strives to encourage the global research community to imbue all clinical and basic research with a sex and gender lens. A wide body of research shows that many health conditions and medications impact men and women differently. Faculty at the Connors Center have published many articles exploring this perspective.

Most recently, Primavera Spagnolo, MD, PhD, scientific director of the Connors Center FiW platform, published a paper in the Annals of Internal Medicine discussing a sex and gender gap in COVID-19. Data studied by Dr. Spagnolo shows that while there are similar numbers of cases between the sexes, men are more likely to die from COVID-19 than women. This gap may be explained by differences in lifestyle, types of care received, behavior and/or biology. Dr. Spagnolo calls for more COVID-19 research to take sex and gender differences into account.

In another recent high-impact paper in Endocrine Reviews, Janet Rich-Edwards, ScD, MPH, director of lifecourse epidemiology at the Connors Center, provides insight into how researchers could more thoughtfully design and conduct studies to include a sex- and gender-informed perspective. Dr. Rich-Edwards suggests that designing studies with sex differences in mind will expand the relevance of biomedical research and promote therapeutic discoveries.

In addition, Deborah Bartz, MD, MPH, director of education at the Connors Center, published a paper in JAMA Internal Medicine that proposes all clinicians consider incorporating a sex and gender lens in their clinical practices. This includes recognizing the biological and environmental factors that affect the course of diseases in women and men. Dr. Bartz suggests that including such a sex and gender lens could optimize clinical care and improve the health of women and men.

“The visionary research done by the faculty of the Connors Center is emblematic of the work the Brigham is doing to transform the future of healthcare,” said Dr. Joffe. “Through research, clinical innovation and advocacy, the Connors Center is making progress in improving all areas of women’s health nationally and globally.”

Improving Women’s Health through Translational Research

In June 2020, the NIH awarded the Connors Center a five-year, $9 million grant for Specialized Centers of Research Excellence on Sex Differences (U54 SCORE grant) to examine the effects of stress on postmenopausal women. The Connors Center will use the grant to support research studying how stress affects women’s physical and mental well-being after menopause and how stress is related to sleep.

“Across a woman’s lifespan, exposure to stress is connected with a variety of health problems, such as mood, poor sleep, fatigue, weight gain, cardiovascular issues and hot flashes,” said Dr. Joffe, principal investigator on the grant. “We want to understand how and where in the brain stress is processed, the neurochemical changes that take place, and the neural processes that connect stress with these adverse outcomes in women.”

Dr. Joffe also leads a five-year NIH grant studying a common sleep issue in middle-aged women, known as sleep fragmentation or interrupted sleep (e.g., waking up at night due to hot flashes). The project examines how fragmented sleep in women affects appetite, hormonal changes and weight gain.

“The Brigham has a rich history steeped in women’s health and sex-differences discoveries,” said Dr. Joffe. “The fact that the Connors Center has been awarded these national-level grants is a testament to our broad capacity for research and our ability to organize across disciplines to innovate at the margins of our varied areas of expertise.”

Investigating Stress-Related Psychiatric Disorders

Over the last 10 years, Dr. Spagnolo’s research has focused on understanding the brain processes that drive stress-related psychiatric disorders, spanning from addiction to post-traumatic stress disorder (PTSD). Most recently, she has focused on functional neurological disorders, also known as conversion disorders.

“Functional neurological disorders disproportionally affect women and are thought to emerge from an abnormal interaction between processes in the brain that control emotion processing and motor function,” said Dr. Spagnolo.

Before joining the Brigham, Dr. Spagnolo completed the first proof-of-concept study aimed at targeting these impaired brain processes using a noninvasive neurostimulation intervention known as transcranial magnetic stimulation (TMS). The study showed that abnormal areas of the brain could be influenced with TMS.

In a recent study, Dr. Spagnolo showed that malfunctions in these brain processes are influenced by genetic factors in patients with functional neurological disorders. Dr. Spagnolo is now working with Gaston Baslet, MD, and others at the Brigham to launch a larger clinical trial to use TMS as a therapeutic tool in patients with this disorder.

Supporting the Next Generation of Women’s Health Experts

To encourage and support emerging leaders in sex- and gender-differences research, the Connors Center provides research awards and fellowships to faculty and trainees for whom seed funds will accelerate their research and clinical work in this area.

Among the many educational and training programs the Connors Center offers to support young investigators is the Global Women’s Health Fellowship Award. Research supported by these fellowships has led to the rollout of human papillomavirus (HPV) vaccine strategies in South Africa and new methods of improving contraception in Uganda. During 2019 and 2020, Brigham researcher Maria Nardell, MD, used her Global Women’s Health Fellowship to develop a youth treatment program in South Africa that offers educational and counseling sessions to young women and men newly diagnosed with human immunodeficiency virus (HIV).

“In the next five to ten years, it’s my hope that, within the Brigham and across the larger healthcare community, we will all start to think more about sex and gender, in the same way we do with age,” said Dr. Joffe. “And I hope this way of thinking about sex differences can be incorporated into how new treatments are developed and incorporated into the care we provide for both women and men.”