This essay is part of a series exploring what is required for scientific progress to be made in our understanding of women’s health and our ability to treat the conditions that impact the lives of women everywhere. Learn more about why this is necessary and explore the other challenges and topics.
Clinical Research Often Ignores Women
Women are participating in clinical trials whether they know it or not. It happens after a drug has been approved by the FDA and is being used to treat women for the first time.
Scientific research has historically focused on male anatomy as the standard and assumed women are just slightly smaller, more hormonal versions of men. The result is that for many conditions where we have treatments (heart disease, diabetes, neurological conditions, etc) we actually have a good understanding of how men experience these conditions, but not women. We’ve gotten here because female models have historically been excluded from basic research, biological sex has not been considered or analyzed as a variable, and women have been excluded from clinical research for decades.
What is clinical research and why are women excluded?
Clinical research occurs after scientists have identified a possible therapeutic that they believe will work on humans. It is generally conducted by private companies in the pharmaceutical industry or by biotech startups and is privately funded.
Clinical research is very risky and 90% of therapeutics will fail during clinical trials. It is estimated that it costs between $985 million and $1,336 million to develop a successful treatment.¹
Clinical research also faces many challenges when it comes to women’s health.
Women’s inclusion in clinical trials has been controversial since pregnant women in Europe in the 1950s were prescribed Thalidomide to help with nausea resulting in severe birth defects in thousands of children. In 1977, the FDA responded to this tragedy by banning women of childbearing years from participating in clinical research. This ban was overturned in 1993, however, protecting the lives and health of the unborn is not the only reason that women have been excluded from clinical research.²
Similar to how female cell lines and mice are excluded from basic research, women have been historically viewed as “confounding and more expensive test subjects because of their fluctuating hormone levels.”³ Additionally, the assumption has been made that women would have the same response as men to therapeutics as they are assumed to be smaller versions of men. These beliefs have strongly influenced their exclusion.⁴
The result is that for decades women have been understudied and underrepresented in clinical trials. When they have been included, the results of the trials were often not disaggregated by sex until 1998 when the FDA required it in trial results. It was not required by the NIH for studies they fund until 2016. Even with these requirements women’s health is not always taken into consideration, as was seen with the Covid vaccination trials which included women but did not collect data on female-specific questions such as the possible side effects on menstruation.
What’s the problem with excluding women?
As a result of this historic exclusion, we lack an understanding of how most drugs affect women. Recent studies have shown that women respond much better to SSRIs (antidepressants),⁵ much more strongly to Ambien,⁶ and we are beginning to look into how they respond differently to cardiovascular treatments.⁷ Dr. Liz O’Day explains that “Women tend to have lower body weight, slower gastrointestinal motility, differential intestinal enzyme activity and slower kidney filtration, which adds up to mean that drugs typically linger in women longer than men.” Additionally, for other drugs, such as SSRIs, it is believed that hormones result in women and men responding differently to the same drugs.
In a review of drugs pulled from the market between 1997 and 2001, the US Government Accountability Office found that 80% were pulled due to adverse effects in women.⁸ As recently as 2018, studies have shown that “women have a 50–70% greater risk of suffering from adverse drug reactions (ADRs) compared to men, and patients admitted to hospital with an ADR are in 60% of the cases women.”⁹
It’s even worse for pregnant women.
Beyond this glaring lack of understanding of how women will respond to most treatments, pregnant women continue to be severely understudied. Ethically, it is easy to understand why there is a hesitation to test medications on pregnant women and risk the health of the fetus. However, having no information doesn’t solve the problem.
Depression is estimated to affect 9–16% of pregnant women and untreated depression in pregnancy “can adversely affect maternal health and increase the risk of preeclampsia and eclampsia, as well as of subsequent postnatal depression, which can lead to disruption of the mother-child relationship.”
The most common treatment for depression is the prescription of SSRIs which approximately 2–3% of pregnant women take. These medications have been associated with a host of negative side effects related to “premature birth, decreased bodyweight of the child, intrauterine growth retardation, neonatal adaptive syndrome, and persistent pulmonary hypertension.” However, “the most recent meta-analyses and reviews suggest that the risks of antidepressant intake during pregnancy for fetal/congenital malformations are small or non-existent, and the risk for poor maternal and fetal outcomes are small to medium.”¹⁰
What is a pregnant woman supposed to do with this information?
For other conditions, such as asthma, which I know about from my own experience, the drugs are not approved for use during pregnancy having never been studied. However, in the wise words of my doctor, “The benefits of you continuing to breathe are greater to the baby than the possible side effects of the drugs.” We do not include pregnant women in clinical trials, nor do we collect the data associated with pregnant women who use unsanctioned treatments to stay healthy. The result is that women are left to make decisions on their own, with the guidance of their doctors, without any data that could assist in the decision-making.
Clinical trials are hard and risky.
Outside of a lack of data on women, clinical trials in general face many other challenges. They are very expensive to run, struggle to recruit and retain patients (especially diverse patient populations),¹¹ and the results of 32% of NIH-funded trials are never shared.¹² Additionally, current technology used to manage and run trials is outdated. While the need for improved systems has been recognized and many companies are making strides in this space, academic researchers do not have the funding to purchase these new tools, which are largely built for and sold to industry researchers.
There are decades of clinical research that did not include women and pregnant women are still not included. The result is a serious lack of information about how different therapeutics will impact women and significantly more adverse drug reactions are suffered by women. The reality is women are participating in clinical trials whether they know it or not. It’s just happening after a drug has been approved by the FDA when it is being used to treat women for the first time.
Next in the series:
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Footnotes:
- https://pubmed.ncbi.nlm.nih.gov/32125404/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800017/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800017/
- https://www.google.com/books/edition/Exploring_the_Biological_Contributions_t/KDicAgAAQBAJ?hl=en&gbpv=0
- https://journals.lww.com/psychopharmacology/Abstract/2005/08000/Sex_Differences_in_Antidepressant_Response_in.5.aspx
- https://pubmed.ncbi.nlm.nih.gov/10773013/
- https://academic.oup.com/ehjcvp/article/3/3/163/3058007
- https://www.gao.gov/products/gao-01-286r
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096710/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096863/
- https://www.sciencedirect.com/science/article/pii/S0146280618301889
- https://www.bmj.com/content/344/bmj.d7292
