This learning scenario, developed by the NYU Langone’s High School Bioethics Project, asks students to understand the historical exclusion of women from medical research and the reasons why. We also explore the benefits and drawbacks of sex equality in medical research and the next steps in analyzing sex-equal research.

Curriculum Integration Ideas

This unit may be used in biology, social science, and women’s studies classes.

Balancing the Use of Male and Female Specimens in Biomedical Research

In 2014, the National Institutes of Health (NIH) introduced a new policy requiring a balanced use of male and female specimens throughout the stages of biomedical research. The policy move to include female specimens in early stages of research came 20 years after the implementation of the NIH Revitalization Act of 1993, which mandated the inclusion of women in NIH-funded clinical research. The act was largely focused on including women in drug trials, from which they had been excluded for decades, and the 2014 policy pushes sex-equal inclusion to all levels of research, from female cell and specimen inclusion to female participation in human trials.

Historically, medical research and drug trials have used male cell and animal specimens, and drugs have been tested on male participants. The results of medical tests on men, specifically white men, are generalized and seen as applicable to all other groups, even without trials to seek out potential differences. This norm has historically had adverse effects on racial minorities and women.

Additionally, “a lack of systematic and consistent inclusion of women in NIH-supported clinical research could result in clinical decisions being made about healthcare for women based solely on findings from studies of men—without any evidence that they were applicable to women.”¹ Over the past few decades, the majority of drugs removed from the market were found to have more adverse effects on women than men. Could this be because of unsatisfactory inclusion of women in testing before drugs are brought to market?

Why Have Studies Excluded Women?

Women have been excluded at multiple levels of medical research for a variety of reasons. The exclusion of women in biomedical research is rooted in the idea of male as the scientific default, meaning that the inclusion of women and females is “perceived as bringing complexity” to research.

Including female trial participants and female cells requires further work and analysis to understand potential differences, which has been perceived as slowing down research processes and met with resistance by researchers. Additionally, there are concerns about the interference of hormones from the female reproductive (estrus) cycle. But since more than 50 percent of humans have an estrus cycle and this affects their health and reactions to drugs, it is important to make drugs that take women’s menstrual cycles into consideration.

Another reason for the exclusion of women has to do with concerns over reproduction. Some researchers fear that unknown side effects of drugs will have adverse effects on the reproductive capabilities of women. This concern is not unfounded—in the 1950s and 1960s, the use of a popular insomnia drug called thalidomide in pregnant women resulted in thousands of babies born with severe birth defects. The thalidomide babies are used as an example of the potential harms of including women of reproductive age in medical testing, particularly at an early stage when the safety of a particular drug is not yet known.

For these reasons, a U.S. Food and Drug Administration (FDA) regulation in place between 1977 and 1993 specifically excluded women of reproductive age. Today, institutional review boards (IRBs) make decisions about women’s participation based on the specific drug in question. The exclusion of women based on their reproductive abilities is rooted in a cultural belief that prioritizes women’s abilities to reproduce over their health outside of reproduction and their general quality of life.

The historical exclusion of women as research participants may have come from a lack of women and people of color being represented in the medical and scientific fields for much of the 20th century. Indeed, professions in the medical field have long been held by white men. In 2008, 75 percent of practicing doctors were white.² In 2018, 64 percent of practicing doctors were men.³ Other reasons for exclusion were more radical, such as the lack of women’s restrooms in research facilities. This fact, too, points to the lack of women in medical research positions.

Consequences of Excluding Female Participants and Cells

Excluding female human participants and cells from the research process can and has had serious impacts on women’s health. As previously mentioned, nearly 50 percent of the drugs that are removed from the market are removed as a result of their negative side effects on women—could this be avoided by including women in pre-market clinical trials?

Comparing Drug Reactions in Women and Men

One example of the consequences of female exclusion can be seen in the case of the popular sleep drug Ambien^®. In 2009 and 2010, there were more than 42,000 emergency department visits resulting from an adverse reaction to the drug⁴; more than two thirds of these were women. Nearly half of the people who sought emergency care were admitted to the hospital, and more than a quarter were admitted to the intensive care unit.

The reactions to the drug were found to be a result of a dosing problem—women as well as men of lower body weight were given a dose that was too high to be safe. Had a systematic analysis comparing female and male reactions to the drug been done during trials, thousands of people, mostly women, may have been able to avoid serious health issues and emergency department visits.

Clinical Testing of All Sexes and Medical Breakthroughs

The case of phenylpropanolamine, an added component of many over-the-counter decongestants, provides another example of the consequences of female exclusion in medical testing. In 2000, the FDA made efforts to remove phenylpropanolamine from over-the-counter medications because of “a reported increased risk of bleeding into the brain or into tissue around the brain in women but not in men.”⁵ If this component had been properly tested in both sexes, this effect may have been found before it became a widespread ingredient in many drugs.

Female exclusion has effects beyond drugs harming women once they’ve already been placed on the market. It also has the potential to prevent important medical breakthroughs. One study seeking treatment for drug addiction found that the drug guanfacine had an effect on drug cravings in female rats, but not male rats. The findings of this research have recently been translated to humans with promising results for women.

Cardiovascular Disease in Women and Men

Furthermore, cardiovascular disease (CVD) is the leading cause of death among women in America, resulting in 400,000 deaths every year.⁶ Women older than 45 are 5 percent less likely than their male counterparts to survive a year after a heart attack. Additionally, women are less likely than their male counterparts to receive aggressive diagnosis and treatment for CVD.

One analysis of FDA-approved CVD-related devices found that only one third of test subjects were women. Heart attacks often result from CVD. While men most commonly experience chest pain from heart attacks, women often feel tightness in their arms. Because symptoms can be different and male symptoms are more largely publicized, women often do not recognize that they are having heart attacks and, consequently, do not seek the necessary medical care.

Mainstream media portrays most heart attack sufferers as men, so people know what heart attack symptoms look like for men, but not necessarily for women. It is also important to note that while 36 percent of white women have CVD, the condition affects a higher proportion—48 percent—of Black women. Thus, both race and sex play an important role in understanding how CVD affects women.

Equalizing Gender in Research Improves Women’s Health

Although women make up more than 50 percent of the world’s population, their bodies and minds have been historically minimized in comparison with those of men. Specifically with regard to health, the male body has been given more attention as the focus of studies and their applicable results. Prioritizing women’s reproductive abilities over their overall health has left women in a medically disadvantaged position that needs to be rectified through equitable health resource allocation and equal inclusion of women in contemporary medical testing.

Giving drugs to populations that have not been adequately tested on them can be viewed as both negligent and reckless, and it has proven to be extraordinarily harmful over the past few decades. The NIH’s 2014 rule that aims to equalize gender in biomedical research is an important step in improving women’s health in America, but much more needs to be done. With rules on inclusion and more women entering the healthcare field every day, it is reasonable to believe that serious improvements in women’s health are on the horizon.

This brief was written by Ella Sklaw as part of the 2017 Summer Internship Program at NYU Langone’s Division of Medical Ethics.

References

1. Mazure CM and Jones DP. Twenty years and still counting: Including women as participants and studying sex and gender in biomedical research. BMC Women’s Health. 2015. DOI.
2. Castillo-Page L. Diversity in the Physician Workforce: Facts & Figures 2010. Association of American Medical Colleges. 2010.
3. Young A … Dugan M. FSMB census of actively licensed physicians in the United States, 2018. J Med Regul. 2019. DOI.
4. ER visits related to Zolpidem and Psychiatric Medications. Patient Safety Solutions. 2014.
5. Pollitzer E. Cell sex matters. Nature. 2013. DOI.
6. Garcia M … Manson JE. Cardiovascular disease in women: Clinical perspectives. Circ Res. 2016. DOI .