Why do women have more adverse reactions to drugs than men?

Men outnumber women in clinical trials, which means research doesn't reflect the female experience with medications.

Anna Sharratt October 9, 2020
scientists in a lab

More men in clinical trials means inaccurate data. GETTY

In case you thought the list of the number of ways men and women are different couldn’t get any longer, we can now add adverse reactions to medications.

Part of the reason for this is that in clinical trials, men vastly outnumber women. And the data — reflective of the male experience — is used by doctors and patients to make decisions about prescribing.

“While doctors currently look at information about side effects when prescribing drugs, few are aware of how those effects change with respect to sex,” says Payal Chandak, a senior biomedical informatics major at Columbia University. “Physicians need to become conscious of sex differences in drug response while prescribing medication.

It’s why Chandak and a team of researchers recently developed an algorithm that can effectively predict how adverse reactions will affect both sexes. AwareDX — which stands for Analysing Women At Risk for Experiencing Drug toXicity — a machine learning algorithm that identifies and predicts differences in adverse drug effects between men and women, works by analyzing FDA adverse reaction reports from the past 50 years. It corrects this gender bias, levelling the playing field when it comes to this type of medication reporting. The findings are reported in Cell Press.

One of the lead authors, Nicholas Tatonetti, an associate professor of biomedical informatics at Columbia, says that the skewed data stems from gender selection in mouse studies.

“Rather than adjust for hormonal differences between male and female mice, researchers simply excluded the females from their study,” he says, adding that this thinking also affected the designs of early human drug studies. “Until the early nineties, the FDA classified women as a special ‘subgroup’ of clinical trials, much like children or senior citizens would be. This meant that they were largely excluded from prospective drug safety studies,” he says.


It also means that the safety profiles of drugs may not be reliable for women who often have very different reactions to medications than men. For example, certain sleep aids like Ambien are metabolized at a much slower rate in women. Women also tend to have a lower body weight, smaller organ size and a higher percentage of body fat, which affects the absorption of drugs. And women are more likely to take drugs concurrently. These differences can have a big impact on women’s quality of life and health, say the authors.

Tatonetti says the research his team has released will have to be validated before it can be used. But he says the findings to date is available for free on their lab website. He hopes that the study is the first step in ensuring that the different genders are equally represented when it comes to medication safety profiles.

“It is critical for clinical trials to reflect the diversity of our population,” says Chandak. “This is not just for sex, but also for race, gender, and ethnicity.”



