- Experts say women are underrepresented in clinical trials for new medications.
- They say this sometimes results in women having more side effects to drugs due to incorrect dosages or biological differences.
- Experts maintain that a greater effort must be made to increase the number of women in trials, especially in early phases.
Women are at greater risk for adverse side effects from medications due to a lack of female representation in clinical trials.
That’s according to recent research on the issue.
In one study, researchers from the University of California, Berkeley, and the University of Chicago analyzed data from thousands of articles from medical journals.
They say they found a gender gap in drug doses for 86 medications approved by the Food and Drug Administration (FDA).
“Sex inequality hides in plain sight today: most drugs are prescribed to women and men at the same dose,” the study authors wrote. “Many currently prescribed drugs were approved by the [FDA] prior to 1993, with inadequate enrollment of female animals in preclinical research and of women in clinical trials.”
It was the adverse effects on women from Ambien, a popular sleep medicine, that sparked the study.
Irving Zucker, PhD, lead author of the research and a professor emeritus of psychology and integrative biology at Berkeley, told Healthline, “The immediate impetus for me was the finding that the sedative/hypnotic drug zolpidem (Ambien), a widely used sleep medication, was causing serious side effects in women, including increased traffic accidents the morning after taking the drug.
“The standard dose produced much higher blood concentrations and longer drug elimination times in women than men. The [FDA] then issued a directive that women should be given half the standard dose administered to men,” Zucker explained.
“I wondered if there were other drugs that also had a robust pharmacokinetic (what the body does to a drug) sex difference, with women sustaining higher blood concentrations than men and whether this could contribute to the known increased risks to drug side effects in women.”
What the research revealed
Zucker, along with his co-author Brian Prendergast, PhD, a professor at the University of Chicago, analyzed studies in which women were given the same drug dosage as men.
They reported that in more than 90 percent of cases, women experienced stronger side effects than men and experienced adverse drug reactions at nearly twice the rate of men.
“I don’t believe anyone can reasonably find this acceptable.Some have tried to explain this in part as women have a lower threshold for reporting adverse drug effects, but much evidence suggests this is not the cause of the sex difference in adverse drug reactions,” Zucker said.
Nancy Pire-Smerkanich, DRSc, is an assistant professor of regulatory and quality sciences in the School of Pharmacy at the University of Southern California. She says the results of the research aren’t surprising.
“Men and women are different in the way they metabolize or process drugs,” Pire-Smerkanich told Healthline. “In women, the pharmacokinetics can be affected by several factors, including higher body fat composition, lower body weight, slower GI, less intestinal enzymatic activity, and slower kidney function.
“For example,” she added, “while both men and women have the same types of enzymes… that metabolize drugs, there are sex-dependent differences in addition to genetic differences.”
Pire-Smerkanich explained, “Men and women may be different in the way they respond to certain drugs. The pharmacodynamics (what the drug does to the body) can be affected by many factors, including sex hormones, which can fluctuate due to menstruation, pregnancy, menopause, [and] oral contraceptives. Other factors include the environmental differences and disparities in the practice of medicine between men and women.”
Exclusion from clinical trials
For decades, women were often excluded from clinical drug trials.
This was based in part on the unsubstantiated belief that fluctuations in female hormones would make women difficult to study, Zucker argues.
There were also concerns surrounding women of childbearing age in clinical trials.
“Women of childbearing ages were long excluded because of concerns that drugs could harm fetuses, as occurred with the drug thalidomide that produced severe limb abnormalities and diethylstilbestrol that increased cancer risks in children exposed to the drug during gestation,” Zucker said.
Although there’s been an increase in women in clinical trials in recent years, Pire-Smerkanich says there are still problems with female representation in early phases of drug trials.
“Women are actually well represented in the later stage trials, those known as Phase 3 studies,” she said. “However, the dosing regimens used in later stage studies are based on the pharmacokinetic data collected in the early trials, where women continue to be underrepresented.
“This is not just about metabolism or breaking down drugs but also what happens to them next — where do they go? Do they get absorbed? Do they get distributed or moved around? And how do they leave the body as excretions?”
Pire-Smerkanich added, “The early phase studies are also where we learn about how the drug works in the body, so it would be important to include women as early as possible in the drug development process.”
What needs to be done
Dr. Judith Currier, a professor of medicine at the University of California, Los Angeles, says more work needs to be done to address the gender gap in clinical trials.
“It’s an area of medicine that we need to put more focus on, and we need to ensure that women are involved and included in clinical studies of medications and that they participate,” she told Healthline.
“We have to be smart about it in terms of using the knowledge we have about pharmacology to understand the medications where the potential for differences are greatest,” Currier added.
Pire-Smerkanich says women are willing to participate in drug trials, as long as they’re informed of the risks involved.
“Women need to be studied earlier in the drug development process and throughout the life cycle, and I think researchers are interested in doing this. Whether they are always supported in these efforts is another unknown,” she said.
“What I do believe is that women are willing to be part of the process and can contribute to our understanding of drugs. [They] just need to be made aware of the need and how they can contribute because as a ‘subgroup’ we have tremendous potential.”
