Why We Know So Little About Women’s Health

Doctors have historically viewed women's bodies as atypical and men's as the norm.
This is despite women making up nearly half the global population and outnumbering men in the U.S. since 1946.
Policy and social changes in the 1990s have started to address this, but women are still underrepresented in research.
Researchers sometimes avoid studying female mice due to the costs of housing both sexes and concerns about fluctuating hormones.
Historical bias and policies to protect unborn children have limited the understanding of how women experience disease and how to treat them.

Failure to study medications in a broad sampling of women contributes to health care disparities.
Biological sex can affect physiological, metabolic, hormonal, and cellular differences, influencing how diseases present and the effectiveness of treatments.
Women experience adverse effects from medications at twice the rate of men.
A 2013 study found that women with metal hip replacements were $29\%$ more likely than men to experience implant failure, possibly due to anatomical differences.
Heart disease is the leading cause of death in the U.S. for both men and women, but the medical field only recognized that women experience different symptoms in 1999 when the American Heart Association published a Guide to Preventive Cardiology for Women.
Women are less likely to receive appropriate prevention and management of heart disease due to gender bias.

Barbara Bierer, MD, emphasizes the importance of studying women to understand product safety and effectiveness.
Martha Gulati, MD, argues that women should not be considered a 'special population' in research, as they make up the majority of the population (51%).

Women were already poorly represented in medical research before the 1970s.
In 1977, the FDA created a policy to exclude women of reproductive potential from Phase 1 and 2 clinical trials unless they had a life-threatening condition.
This was a reaction to the thalidomide tragedy, where thousands of pregnant women in Europe and Australia who took the drug for morning sickness experienced severe birth defects in their babies.
Thalidomide had been tested and approved for its sedative effects, though it was never approved in the U.S.
The FDA’s policy was broadly interpreted, excluding nearly all premenopausal women, even those using birth control or abstaining from sex.
In 1986, the policy was revisited, and in 1993, the U.S. Congress passed a law requiring the inclusion of women in clinical research.
As recently as 2019, women accounted for roughly $40\%$ of participants in clinical trials for cancer, cardiovascular disease, and psychiatric disorders, despite representing $51\%$ of the U.S. population.
Pregnant people are commonly excluded from trials, leading to a lack of information about medications and interventions during pregnancy.

1962: After thalidomide results in more than $10,000$ deaths and birth defects, the United States strengthens the authority of the FDA.
1977: The FDA creates a guideline to exclude women of reproductive potential from early phase clinical research, except for life-threatening conditions.
1986: An NIH advisory committee recommends that women be included in medical research studies.
1990: The NIH establishes the Office of Research on Women’s Health to advance research into women’s health and increase representation of women in clinical research.
1991: Bernadine Healy, MD, is appointed the first female director of the NIH.
1993: The FDA reverses its 1977 guidance, mandating the inclusion of women in research unless there is a justification for exclusion.
1993: The U.S. Congress passes a law requiring inclusion of women in NIH-sponsored clinical trials.
1994: The FDA establishes the Office of Women’s Health to promote the inclusion of women in clinical trials and the advancement of women’s health care.
2001: The Institute of Medicine releases a report demonstrating how sex difference influences biology and should be studied as a variable in clinical research.
2022: A Harvard Medical School study finds that women, as of 2019, were still substantially underrepresented in clinical trials for leading diseases.

Clinical trial data often do not report the intersection of biological sex and race.
Systematic reviews show significant underrepresentation of women of color in clinical trials.

Danielle Mitchell, CEO and founder of Black Women in Clinical Research, aims to bridge the gap between Black communities and the clinical research field.
Strategies include broadening the scope of hiring at research sites and having tough conversations about past events to build trust.

Maria Brooks, PhD, notes progress in increasing the inclusion of women in medical research over the last 30 years.
There is still ground to cover to achieve equity between men and women, particularly women of color.
Strategies to move the needle include:
- Attracting and retaining a diverse group of women in leadership roles for medical and clinical research.
- Incorporating how biological sex differences affect medical care into medical education.
- More robust and inclusive research and data collection.

A study analyzing the sex of principal investigators for cardiovascular clinical trials found that just $18\%$ of the trials were led by women, but those led by women enrolled more female participants.

Gulati gives lectures at medical schools about sex differences in cardiology care and notes that many students are learning about these differences for the first time.
Often, male biology is still taught as the “default,” and learning about female biology is considered “special interest.”

In 2016, the NIH instituted a policy requiring researchers with NIH funding to collect data on biological sex differences in preclinical research and animal testing, analyze the data, and report on differences in the findings.
There is a lack of accountability when researchers don’t follow through on their commitment to enroll a certain percentage of women in their clinical trials.
Researchers can make further progress by designing trials that are more flexible and accessible for people with caretaking responsibilities or transportation issues.