Why are Women More Likely to Have Adverse Drug Reactions Than Men?

Men and women experience diseases differently. This includes how the disease progresses, the duration and severity of symptoms, and how effective treatment alternatives are. Unfortunately, because females have historically been underrepresented in biomedical research, we don't know as much about how diseases affect women. This means that most research studies are carried out on male cells, including preclinical research mostly done with male experimental animals like mice. The results are then mostly erroneously assumed to be true for women. This has had unbecoming consequences and has been especially linked to female underrepresentation in clinical drug trials. A study by the University of California, Berkeley, and the University of Chicago found a drug dose-related gender gap in over 86 FDA-approved medications! Indeed, research has shown that women are 50–75% more likely to have adverse drug reactions than men, and not much was known about the reason why in the past. Fortunately, researchers may have just found the answer to why women experience more adverse reactions and side effects from drugs. This can help encourage more measures to protect women from ADRs and even prevent them in the future. Read to learn more.

What are Adverse Drug Reactions (ADRs)

Every year, over 1.3 million people visit the emergency room due to adverse drug reactions (ADRs), which account for about 5% of all unplanned hospital admissions. You can think of ADRs as any unwanted, unpleasant, or dangerous response gotten from a drug when taken at the right doses. Adverse drug reactions are a very serious public health problem, and it has been found that women are more likely to have them than men. For example, from January 1, 1997, to December 31, 2000, the FDA took 10 drugs off the market, eight of which were taken off because they caused more side effects in women than men. So, newsflash, ADRs are a serious issue, and women seem to be more at the receiving end. The question is, why is this so? Why are women more likely to have adverse drug reactions, and what can be done about it?  

While there have been a number of theories, no definite cause has been discovered for the higher rates of adverse drug reactions in women. However, researchers at the Australian National University may just have found the answer to the question. Before we look at that, let’s see some of the issues that have been obstacles to the explanation of why women suffer more from adverse drug reactions.

Hasty generalization and Gender Bias

Most biomedical research is carried out on males, mice, and humans alike. The results of these studies are often simply generalized without modification for females, but this isn’t always correct and points to a gender bias in research, especially the biomedical kind. In fact, in one prominent example of adverse drug reactions in women involving the sleep medication Zolpidem, sex-based dose adjustments by the FDA weren't made until many years after the drug was first sold, when women who took the standard dose for men showed signs of cognitive problems.

Furthermore, in 2016, the National Institutes of Health made it a requirement for grant applicants to find both male and female participants for their studies. This was in response to the widespread bias toward men in both human and animal studies. However, while there have been more female inclusion in drug trials in recent years, many newer studies still don't analyze the data for sex differences, and this continues to stand in the way of knowledge of disease progression and drug efficacy in women.

Different Doesn’t Always Mean Smaller

It’s been pretty clear for quite some time that women experience more adverse reactions to drugs than men do, and previous studies postulated that this was because of differences in body weight. While this has applied to certain medications, physiological findings have not always shown it to be true. Previous studies have also shown that physiological differences between men and women affect how medications are absorbed, distributed, digested, and eliminated from the body. So, body weight might not be enough to explain why women are more likely to have bad reactions to medicines. A recent study in mice busts the myth that women's bodies are just smaller versions of men's. Instead, it shows that there are some sex differences in traits that could help explain why drug reactions affect men and women differently.

The Answer? A for Allometry

Researchers at the Australian National University may have finally been able to explain why women suffer more from adverse drug reactions. They did this with the help of a biological method termed “allometry,” which helps examine the link between a trait of interest and body size on a log scale. The researchers applied the allometry analyses to over 300 preclinical traits in males and females, capturing over two million data points using mice, which is an established preclinical model. And from their findings, it was pretty clear that the idea of women just being smaller versions of men is, at best, an oversimplification, and ignoring the differences in traits has serious consequences, or as stated by study head Laura Wilson, Ph.D., “Ignoring these differences in some cases, such as measures of blood cells, bones, and organs, could result in missing a lot of the population variation for a particular trait: up to 32% for females and 46% for males. This complexity means we need to consider sex differences for drug dosing on a case-by-case basis.”

The Need for More Research

Adverse drug reactions are costly and have serious consequences, as shown in a recent Australian study estimating that up to 250,000 hospital admissions are related to medication and cost the healthcare system a whopping $1.4 billion a year. Furthermore, studies have also associated drug reactions with a longer hospital stay, with an average of up to 8 days spent in the hospital! It is clear that adverse reactions are no joke, and women seem to be getting the short end of the stick. The results of the study highlight the need for increased attention to measuring how and why the sexes differ in biomedical research.

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