In recognition of International Women’s Day (March 8), Clinical Trials Ontario is pleased to feature this Talk Clinical Trials blog by Dr. Cara Tannenbaum, Professor of Medicine at the Université de Montréal and former Scientific Director of the CIHR Institute of Gender and Health.
Most of us assume a simple thing: when a medication is approved, it’s been tested properly on everyone who might take it. Men and women alike. Young and old. Seems obvious, right?
But here’s the uncomfortable truth: for much of modern medical history, that hasn’t been the case. Many medications—both old and new—were tested mostly on men. Women were often left out. Not because anyone thought women didn’t matter, but because science tried (and failed) to “protect” them.
How did this happen?
In the 1950- 1960s, a drug called thalidomide was prescribed to pregnant women to treat morning sickness. Thalidomide was not tested in pregnant women before it was marketed and distributed globally. It caused severe birth abnormalities in thousands of babies. The tragedy shook medicine to its core. Regulators responded with fear and caution: women of childbearing age were broadly excluded from clinical trials.
The intention was good—protect women and unborn babies. But the result was deeply flawed.
Because here’s the thing: pregnant women get sick, and sick women get pregnant.
By excluding women from trials, we ended up in a strange and dangerous situation. Medications came onto the market without anyone really knowing whether they worked the same way in women, whether they were safe in women or whether women needed different doses. So women still took the drugs—just without evidence tailored to them.
The “default male” problem
For decades, drug development relied heavily on male animals in lab studies and young, healthy men in human trials. Why? Researchers worried that female animals might get pregnant and that hormones would “mess up the data.” So instead of dealing with complexity, they avoided it.
But women are not just smaller versions of men. Women process medications differently. Their smaller kidney size means drugs may leave the body more slowly. Higher fat content means fat-soluble drugs (like sedatives) can build up and last longer. Hormones and oral contraception can affect liver enzymes and drug metabolism. Women’s smaller size on average may mean that doses designed for men are unnecessarily high for them. As a result, women are twice as likely as men to report side effects.
And they’re not being dramatic. A U.S. audit in 2001 looked at drugs withdrawn from the market between 1997 and 2001. The result was alarming: 8 out of 10 had more frequent side effects in women. Some interfered with women’s naturally longer QT interval in the heart, triggering fatal heart rhythm problems. Others were withdrawn because they harmed both sexes—but were prescribed more often to women, such as appetite suppressants.
Why don’t labels warn us?
You might think drug labels would clearly say: “This medication affects women differently.” But they rarely do. In only a few cases have regulators officially recognized that women need lower doses. Most of the time, the dose is “one size fits all,” even though biology says otherwise.
When did things start to change?
In 1993, after growing global awareness of women’s health, including momentum from the Beijing Conference on Women, the U.S. passed the NIH Revitalization Act. It pushed researchers to include women in clinical trials. Since then, things have improved. More women are enrolled. Awareness is higher. There’s a movement toward fairer science.
But the job is far from done. Women still face barriers to participating in clinical trials because of caregiving responsibilities, work schedules, lack of childcare and inflexible trial designs. And here’s the big remaining problem: even when women are included, researchers don’t always analyze men’s and women’s results separately. That step—called sex-disaggregated analysis—is crucial. Without it, we still don’t know if a new drug works better in one sex, if side effects differ or if women might benefit from different doses or alternatives. So we are ending up with more women in trials, but the same blind spots in conclusions.
Why this matters to you
If you’ve ever felt unusually sleepy from a sedative, had strong side effects from a medication or wondered why a drug didn’t work as expected…it may not be “just you.” It may be that the evidence was built on someone else’s biology.
What can you do?
You don’t need a science degree to ask smart questions. If you or someone you care for is considering a clinical trial, you can ask:
- Were female animals included in the early phase research?
- Will the results be analyzed separately for men and women?
- Are side effects reported by sex?
- Have lower doses been tested in women?
These questions help push medicine toward better science—for everyone.
If you or someone you care for is associated with a Canadian clinical trials network, you can ask whether they have policies making sex-disaggregated data mandatory. You can also ask if they have policies that present the results separately for gender diverse or trans groups, and whether they disaggregate the data by ethnicity and age. This way you’ll know if the results of trial apply to you.
The bottom line
Women are not just small men with different hairstyles. They have different hormones, different metabolism, different risks, and different responses to drugs. When clinical trials ignore that, it isn’t just unfair—it’s unsafe. Good medicine depends on good evidence. And good evidence must reflect the people who actually use it. Equality in healthcare doesn’t mean treating everyone the same. It means understanding when biology makes us different—and designing science to match reality.
Learn More
If you would like to learn more about sex and gender and its considerations in research, we encourage you to explore the resources and tools that the CIHR Institute of Gender and Health has available, some of which include: a video about Learning about sex and gender, a resources page that includes a number of resources and tools, and the Institute’s sex and gender modules.