Closing the Medical Research Gap

For centuries, researchers believed that if they understood how a disease affected men, they could simply apply that knowledge to women. Only in the past few decades has the medical profession started to recognize how sex and gender* impact health and illness. Researchers now realize that the same condition can present differently in men and women, and that males and females may respond differently to treatment. Because women were historically left out of medical research, we still know less about how the most widespread diseases like cancer or heart disease affect women, and less about how to prevent, diagnose, or treat these diseases in women.

“It was long assumed that men and male animal models provided the norm for research — even when studying diseases that affect both sexes,” explained Janine Clayton, M.D., director of the Office of Research on Women’s Health at the National Institutes of Health (NIH). As a growing body of evidence indicated otherwise, attitudes about the importance of including women in medical research started to shift. In 1993, Congress passed the NIH Revitalization Act requiring that NIH-funded clinical research include women.

The new law brought progress, but as its 20th anniversary approached, a group of experts came together at the Mary Horrigan Connors Center for Women’s Health at Brigham and Women’s Hospital in Boston to work on a report tracking if, and how, the field of biomedical research had changed. They examined gaps in research for four major medical conditions: cardiovascular disease, lung cancer, depression, and Alzheimer’s disease.

The researchers found that even after the NIH mandated the inclusion of women in clinical research, women’s health continued to be overlooked. For example, cardiovascular disease is the leading cause of death among women (and men). While the number of women in NIH-sponsored clinical trials increased after 1993, in mixed-sex cardiovascular trials, only one-third of the subjects were female, and fewer than one-third of the trials that included women reported outcomes by sex. “With cardiovascular disease, we have the most data on sex differences, but we still don’t understand the biology that underlies those differences. So we have to question — do we have the right diagnosis, and right interventions for women?” said Paula Johnson, M.D., M.P.H., a cardiologist who was chief of the Division of Women’s Health at Brigham and Women’s Hospital and professor of Medicine at Harvard Medical School when the report was published.

The report surfaced other biases in medical research, like the assumption that women were more likely to develop Alzheimer’s disease because they lived longer than men. “That’s just not true — now we know that the difference in prevalence is related to sex hormones at menopause, and has nothing to do with longevity,” said report coauthor Therese Fitzgerald.

One of the consequences of the lack of understanding of how disease impacts women is that clinicians are more likely to dismiss women’s health concerns, or attribute their pain to emotional distress. “Women experience pain differently than men — and there’s a scientific basis for that,” Fitzgerald said. Looking at it clinically, beyond the social construction of women’s pain as emotional, there are actual scientific differences. For example, men and women remember pain differently — men remember pain with a clarity that makes them more sensitive to future pain when they return to the environment where they first experienced the pain, according to a McGill University study published earlier this year. Women, in contrast, do not remember pain this way, and do not exhibit stress the way men do in an environment where they previously experienced pain.

This medical research gap exists, in part, because too often, people think of women’s health as simply their reproductive health. “We need to instead consider ‘the health of women,’ a phrase that encompasses all conditions that affect a woman,” Clayton said. But that doesn’t mean studying diseases related to women’s reproductive health isn’t important.

“This isn’t a race to see if we can get more dollars invested in cardiovascular research at the expense of breast cancer,” Johnson, who is now president of Wellesley College, said. “This is the race to get the most invested in women’s health overall and to obtain the most accurate data possible.” But progress is slow: A 2019 Lancet study based on the analysis of 11.5 million journal articles found that while sex-related reporting increased in clinical medicine and public health research from 1980 to 2016, sex remains largely underreported in biomedical research.

One added challenge is that reporting results that show sex-based differences could be used to reinforce historical stereotypes around the stronger sex or gender. But biomedical researchers cannot avoid studying how brain disease, for example, may impact men and women differently because of archaic (and false) notions about sex differences in intelligence and emotions. Experts say willful ignorance is hardly the answer — because it is such biases about men and women that have contributed to gaps in medical research.

“These biases are not going away,” said Johnson. “[But] as scientists we have to work to untangle complex questions and recognize that there isn’t a simple answer.”

One way to get at the root of the problem is medical education: “It is important for medical school students to understand that sex and gender will have an impact on many aspects of their practice and research,” said Clayton. Yale University, for example, is integrating sex and gender into its medical curriculum. As the medical profession gets better at recognizing how sex and gender impact health, the U.S. will get closer to achieving health equity between men and women.

Ultimately, “the purpose is to focus on the health of women, and to integrate sex and gender into science as routine,” said Johnson.

The Commonwealth Fund has sought to address inequities in health and health care from its inception — in 1941, it awarded George Papanicolaou a grant for his early research that led to the creation of the Pap smear. Now a routine part of gynecological checkups, the Pap smear has saved the lives of millions of women worldwide by cutting death rates from cervical cancer in half. The Fund in 1993 launched a five-year Commission on Women’s Health to explore ways to improve access to health care services, improve mental health treatment, tackle violence and abuse, and address the health needs of adolescent girls. Building on this commitment, in 2018, we published a study on the status of women’s health in the United States compared to other developed countries. This is the first post in a new series of publications on the health of women.