For decades, the world of medicine has operated under a dangerous assumption: that a woman is simply a ‘smaller man’. This belief has shaped everything from the way clinical trials are designed to the way physicians prescribe common medications.
But, this bias is not a harmless oversight. It has been systematically promoted through policies and regulations over decades, and has had lethal consequences and continues to put women’s health at a high risk.
Global reports show that roughly 60 per cent of all reported adverse drug reactions (ADRs) occur in women. And it is not a mere coincidence. These results are based on a research analysis across 96 countries, including India. The study, Reported adverse drug reactions in women and men: Aggregated evidence from globally collected individual case reports during half a century, was published in 2019.
Adverse drug reactions (ADRs) are unwarranted and unintended responses to medications that can range from mild to severe and occasionally pose life-threatening risks. Emerging science and data-based research is showing us that globally women have essentially been given the wrong doses of medicine because we never bothered to test what the right dose should be. And to find out the right dose, there needs to be a fair participation of women in clinical trials for new drugs.
While women make up more than half of the global population, they have been systematically neglected in medical research and clinical trials because of various factors, including historical regulatory bans, structural and social barriers, and concerns regarding pregnancy and foetal risk.
But the biological reality is that men and women are fundamentally different in how they process medicine. Women have distinct hormonal cycles, metabolic rates, immune responses, and even different fat distributions and organ clearance times. All of these factors affect how a drug behaves once it enters the body.
The Missing Half in Clinical Trials
The foundation of modern medicine are clinical trials. The World Health Organization (WHO) defines clinical trials as a type of research that studies new tests and treatments and evaluates their effects on human health outcomes.
For decades, women have been sidelined in these critical studies and continue to be underrepresented in phase I clinical trials. Phase I clinical trials test the safety and tolerability of investigational drugs, often on healthy individuals.
A recent report by not-for-profit research organisation Drugs For Neglected Diseases Initiative (DNDi), titled InSciLead: Gender Inclusive Science, Access & Leadership, points out that women represent less than 30 per cent of participants in industry-sponsored phase I trials for new drugs. This is reflected in an analysis of the new drug trials approved by US Food and Drug Administration (FDA) from 2013 to 2015.
The DNDi notes that the exclusion of women, especially women of childbearing potential, is driven largely by concerns about fertility and the potential risks of teratogenicity (ability of a drug to cause foetal abnormalities or deformities) and fetotoxicity (adverse effects on fetal development caused). Outdated policies have reinforced this imbalance by broadly excluding women.
Many clinical trials mandate that women of childbearing potential use birth control, often specifically requiring long-acting contraceptives as a condition of participation. This is to prevent potential foetal risk. While researchers frame these requirements as a necessary medical safety measure, these preconditions often create significant barriers to participation of women due to cultural taboos and the financial costs associated with accessing these services.
A 2023 research paper in Ethics and Human Research, an international research ethics journal, highlights that sex-based differences in adverse drug reactions are often linked to drug dose, and “pivotal safety information in phase I trials is often insufficiently-and inequitably-captured for females”.
The 2019 study also notes that women are thought to be more at risk for ADRs not only because they use more drugs but… the fact that they use higher doses in relation to their body weight.
Exclusion By Design
This exclusion of women from clinical trials is not an accident; it is rooted in a history of over-protectionism and outdated policies. It started with the thalidomide tragedy in the US.
Thalidomide was a widely used drug in the late 1950s and early 1960s for the treatment of nausea in pregnant women. Thalidomide, a sedative, was never approved for use in the United States. However, the drug was used widely throughout Europe and Canada. Thousands of women who took the drug while pregnant gave birth to babies with horrible limb deformities. This horrific event caused researchers to adopt a cautious approach to female participation in clinical trials.
In 1977, a US FDA policy recommended excluding women of childbearing potential from Phase I and early Phase II drug trials. The policy was broad and recommended excluding even women who used contraception, who were single, or whose husbands were vasectomised.
The intent was to protect potential foetuses from harm, but the effect was the systematic neglect of women’s health. Excluding women from early stages of drug trials led to a shortage of data on how drugs affect women. Many people believed that individual women should be allowed to choose whether to take the risk of participating in research. Although these bans were eventually lifted in the 1990s, the legacy remains entrenched.
Today, pharmaceutical companies still hesitate to include women, citing concerns about hormonal fluctuations or the logistical burden of managing pregnancies during a trial. When women aren’t included in the design and testing of a drug, the result is a massive data gap that puts female patients at risk.
Globally, health organisations have started to recognise the importance of sex and gender in health and disease. Sex differences exist at multiple levels of biology, from genetics upward. For instance, research shows that blood vessels in a woman’s heart are smaller in diameter and much more intricately branched than those of a man. Those differences offer one explanation for why women’s vessels may become blocked in a different pattern than those in men.
Despite ongoing efforts, women’s health remains understudied, and sex, gender, and intersectional factors are infrequently considered when setting research priorities or questions.
For example, a study examining USA’s National Institute of Health (NIH) funding patterns reported that in 2019, of the underfunded diseases (relative to disease prevalence), all but one was female dominant, and of the overfunded diseases, most were male dominant (11 male versus 8 female). Furthermore, compared with female-prevalent diseases, male-prevalent diseases receive nearly twice as much actual and burden-commensurate funding.
The Double Neglect: NTDs and Data Gaps
The problem is even more acute in case of neglected tropical diseases (NTDs) like dengue, leprosy, lymphatic filariasis, leishmaniasis, rabies, snakebite envenoming, etc. These diseases primarily affect the world’s poorest populations, and marginalised women suffer from a 'double neglect'—first as members of an impoverished community and second as women underrepresented in health research.
There is a staggering lack of gender-disaggregated data in epidemiology. For many diseases, data that breaks down infection rates and outcomes by sex is not collected at all. Without this data, health interventions cannot be effectively targeted.
Take dengue, for example. While incidence may seem balanced between the sexes, pregnancy is a major risk factor. The risk of death from dengue is 3.95 times higher for pregnant women than for non-pregnant women of reproductive age.
Similarly, Chagas disease (also known as American trypanosomiasis) is increasingly transmitted from mother to child, which has now become the main path of infection in some regions. Yet, because women have been excluded from research, there is a lack of the necessary evidence to treat them safely during pregnancy.
Perhaps the most glaring gap is the treatment of pregnant and lactating women. Because they are routinely excluded from trials to avoid legal liability, most drug labels carry a standard disclaimer: “Safety in pregnancy not established”.
This leaves expectant mothers and their doctors with an impossible choice: risk taking an untested drug or forgo treatment entirely for a serious illness.
Structural Barriers and the Leadership Gap
Why does this bias persist in 2025? Part of the answer lies in who is leading the research. This is known as the 'XX Paradox': while women make up 70 per cent to 90 per cent of the frontline healthcare workforce, they hold only 25 per cent of leadership positions.
When men dominate the decision-making roles in biomedical research, female-specific health issues often become an afterthought. Preclinical research frequently avoids using female animals because their hormonal cycles are viewed as 'complicating' the data. Furthermore, systemic barriers like caregiving responsibilities and a lack of childcare options make it difficult for women to participate in trials even when they are invited.
Failing to close this gap is not just a matter of fairness; it is the need of the hour to ensure that women and minorities are included in all clinical research. It is time for a shift in research that recognises women as biologically distinct individuals who deserve medical care tailored to their bodies.
As we face future pandemics and the health impacts of climate change—which disproportionately affect women in rural settings—we cannot afford to ignore half the population.
Research organisations like DNDi are working in this direction. They are mandating gender-disaggregated data broken down by sex. Demand for updating regulatory guidelines is also growing. There is a need to move away from the reactionary approach of excluding pregnant women and instead focus on generating the scientific evidence needed to treat them safely.
More women are needed in leadership roles as principal investigators and decision-makers. Studies led by women are more likely to include female participants and address their unique needs. Women from local communities need to be involved in shaping clinical trials. Providing solutions for childcare and transport can remove the practical barriers that keep women away from research.
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