Medical researchers, clinical advocates, and federal policymakers are calling for a structural overhaul of how clinical trials are designed, arguing that merely meeting enrollment quotas for female participants fails to capture how medications and diseases specifically affect women. Across the United States and internationally, experts point out that pooling data from men and women without analyzing biological sex differences, hormonal fluctuations, and life stages leaves major blind spots in modern healthcare. On October 19, 2026, The White House issued a presidential directive establishing a new Women's Health Division within the National Institutes of Health (NIH) within 90 days, aiming to mandate stronger accountability for sex-specific outcomes across all phases of a woman's life.

The push to redesign clinical studies stems from decades of treating the male body as the default baseline in biomedical science. While female enrollment in clinical research has risen over the past three decades, physicians and geneticists warn that underpowered study protocols continue to obscure critical differences in how women metabolize drugs and experience illness.

The Limits of Enrollment Quotas

Historically, women were largely excluded from drug trials, a pattern reinforced after the 1950s thalidomide tragedy—which caused roughly 90,000 miscarriages and left more than 15,000 children with severe birth defects—prompted regulators and researchers to halt drug testing in women, particularly those who were pregnant or nursing, according to Nauka w Polsce. It was not until 1993 that the NIH Revitalization Act mandated the inclusion of women and minorities in all NIH-funded clinical research, accompanied that same year by Food and Drug Administration (FDA) guidance encouraging female participation in early-phase trials.

Despite these mandates, representation remains uneven. According to Drug Discovery News, a 2022 analysis of 1,433 clinical trials covering more than 300,000 participants found that females made up an average of 41.2 percent of enrollees, despite accounting for 51 percent of the US population. Across cardiovascular disease, psychiatric conditions, and cancer trials, women were consistently underrepresented compared to their share of the affected patient population.

Even when women are enrolled, their biological data are often merged with male data rather than evaluated separately. Dr. Kinga Szydłowska, a molecular neurobiologist at the Nencki Institute of Experimental Biology of the Polish Academy of Sciences, noted that in more than 80 percent of studies after women began participating in trials, results were presented collectively without distinguishing by sex.

"While the number of women enrolled in studies has grown, the ability to make meaningful conclusions regarding biological sex differences based upon those enrollments remains limited due to underpowered study designs and an absence of consideration of hormonal status or life stages," Dr. Brian Honeyman, a board-certified physician at Marietta Springs, told Drug Discovery News.

Why Female Physiology Requires Tailored Study Designs

Biological sex influences health outcomes far beyond reproductive anatomy, reaching down to the cellular and genetic levels. Barbara Stranger, PhD, a professor of biomedical informatics at the University of Colorado Anschutz, summarized the issue directly: "Women are not just little men."

A 2020 study published in Science that examined 44 human tissue sources found that 37 percent of human genes showed different expression levels between males and females in at least one tissue, and identified 58 links between genes and human traits driven by sex-specific genetic regulation. These genetic and physiological variations affect immune function, cardiovascular pathways, symptom presentation, and how drugs move through the body.

As Dr. Szydłowska explained, women and men differ in kidney and liver clearance rates, muscle-to-water ratios, and gastric emptying speeds—with a woman's stomach generally emptying food more slowly. These factors alter how quickly a drug reaches peak concentration, which tissues it enters, and how long it stays in the system. When standard drug doses are based on pooled or predominantly male data, doses for women can be set too high. In the case of the sleep medication zolpidem, identifying these pharmacokinetic differences later prompted the FDA to recommend cutting the standard dose for women in half.

Researchers do differ on how broadly sex-specific trial protocols should be applied in practice. According to the University of Colorado Anschutz, relevant subgroup analyses and statistical methods capable of detecting sex differences should be built into the initial study design rather than treated as an afterthought. Meanwhile, Nauka w Polsce reports that recruiting women remains logistically challenging—since trials frequently require contraception for participants of reproductive potential or recruit post-menopausal women—leading to a common practice where medicines are tested in women generally, with additional targeted studies conducted conditionally when a specific need is justified.

Unmet Needs in Chronic Pain and Federal Action

The shortage of female-specific trial data is especially visible in chronic pain and gynecological conditions. Speaking with cannabishealthnews.co.uk ahead of the Cannabis Health Symposium in Frankfurt, phytopharmacist Dr. Shabnam Sarshar highlighted the lack of randomized controlled trials for conditions like endometriosis, menopause, premenstrual dysphoric disorder (PMDD), and fibromyalgia.

In Germany, where roughly two million women live with endometriosis and diagnosis often takes eight to ten years, women represent the majority of patients receiving reimbursed cannabinoid medications for non-cancer pain—accounting for 66.7 percent in BARMER insurance data and 59.8 percent in an accompanying federal survey. Although a 2022 regional survey found that 17 percent of a relevant subgroup self-managing endometriosis with cannabis reported 91 percent better sleep and 90 percent less menstrual pain, Dr. Sarshar emphasized that self-selected patient surveys are no substitute for controlled clinical trials that track how hormonal fluctuations impact drug response.

To address these evidence gaps in the United States, the October 2026 directive from The White House instructs the NIH to coordinate research across all life stages, from infancy and adolescence through pregnancy, midlife, menopause, and aging. The order prioritizes understudied conditions including heart disease, stroke, Alzheimer's disease, autoimmune disorders, endometriosis, fibroids, and polyendocrine metabolic ovary syndrome. While the presidential action outlines federal policy goals and demands stronger accountability for NIH grant recipients regarding sex-as-a-biological-variable guidelines, independent analysts note that the directive sets administrative targets rather than immediately demonstrating altered trial protocols across the pharmaceutical industry.

Frequently Asked Questions

Why is enrolling women in clinical trials not enough on its own?

When clinical trials enroll both men and women but pool their results together without planned subgroup analysis, important biological differences can be masked. If a study does not enroll enough women to achieve statistical power for sex-specific analysis—or fails to track hormonal stages like menstruation, pregnancy, or menopause—researchers cannot accurately determine if a drug works differently or causes higher rates of side effects in women.

Which health factors need to be considered when designing trials for women?

Experts state that trials should account for sex-specific pharmacokinetics (how the liver, kidneys, and digestive tract process drugs), genetic expression differences, and hormonal fluctuations across the lifespan. This includes evaluating how puberty, the menstrual cycle, hormonal contraceptives, pregnancy, lactation, and menopause alter disease pathways and medication efficacy.

How will federal agencies measure whether clinical trial designs actually change?

Under the October 2026 White House directive, the Department of Health and Human Services and the NIH are tasked with establishing a dedicated Women's Health Division within 90 days. This division will work alongside the NIH Office of Research on Women's Health to increase scientific review of understudied female conditions and enforce accountability among NIH grant recipients to ensure they adhere to federal policies accounting for sex as a biological variable.

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