As a scientist, I’ve often wondered: Why do women report more severe side effects from medications? The answer isn’t a medical mystery; it’s historical oversight. For decades, medical research and drug development disproportionately focused on men, disregarding the unique biological and physiological complexities of women. This singular focus created a significant and lasting gender gap in modern medicine.

One Size Doesn’t Fit All

If you’ve ever tried on unisex clothing, you know the fit is rarely perfect. As a scientist, I understand this “one-size-fits-all” approach to drug development has led to major unintended consequences, often leaving women vulnerable to adverse drug reactions.

Up until the early 1990s, women of child-bearing age were frequently excluded from clinical trials for new drugs. While this exclusion was partly intended to protect a potential fetus from unknown harm, the consequence was profound: Medications were developed and dosed using only the male body as the standard. Doctors assumed a drug dose could be simply scaled down based on body weight, overlooking the fact that human physiology is far more complex than a number on a scale.

How Biology Influences Drug Processing

A person’s sex—their biological makeup determined by chromosomes, anatomy and physiology—plays a huge role in pharmacokinetics (how the body processes a drug). It’s important to distinguish this from gender, which refers to social and cultural roles.

For example, women generally have a higher percentage of body fat than men, which directly changes how a drug is processed. Drugs that easily dissolve in fat may be absorbed more slowly but can stay in a woman’s body for longer periods. Differences in metabolic enzyme levels in the liver and how the kidneys function in both sexes can change how quickly a drug is broken down and eliminated from the body. Both factors slow this process (called “clearance rate”) and cause the drug to stay in the body at higher concentrations.

A Wake-Up Call: A Case of Dosage Bias

Hormonal fluctuations are another key biological variable to consider with drug dosing. Estrogen and progesterone can alter the expression and activity of liver enzymes responsible for breaking down up to 75% of all drugs. These hormonal shifts, whether due to the menstrual cycle, pregnancy or hormone therapy, can drastically change a drug’s clearance rate, affecting both its concentration and how well it works.

A well-known example of this oversight is the sleeping pill zolpidem, often sold in the U.S. under the brand name Ambien. Doctors initially prescribed the same dose to everyone, based on studies conducted mostly on men. Women began reporting more severe side effects including next-day drowsiness, dizziness and memory loss because they cleared the drug from their systems slower than men. The problem was so pervasive that in 2013, the Food and Drug Administration issued a public safety announcement, recommending a lower starting dose for women.

The Path to Personalized Medicine

The long-term consequence of male-only clinical trials was a delay in health recovery, increased side effects and ineffective treatments for women. Recognizing this crisis, the National Institutes of Health began requiring researchers to report and account for sex as a biological variable (SABV) in studies beginning in 2015.

The medical and scientific community is now increasingly focused on a personalized health care approach. Modern technology allows us to better interpret how a person’s unique biology, which includes their sex, genetics and metabolic state, influences drug effectiveness and safety. By closing the gender gap in research, we aren’t just improving drug safety but instead we also move medicine towards tailored care and effective treatments for every person.