Gender in the Pharmacy: Does It Matter?

Studies of how women’s and men’s bodies process drugs have turned up mostly minor differences. But some
drugs may be less or more effective in women or cause more side effects, and other variations may await
discovery.

In 1989, a 39-year-old woman blacked out while she and her husband were eating dinner. He rushed her to the
Naval Medical Center in Bethesda, Maryland, where tests showed that her heart had a dangerous irregular
rhythm that can lead to cardiac arrest. Doctors were puzzled: The woman was taking a popular antihistamine,
Seldane, overdoses of which had caused abnormal heart rhythm, yet she was taking the recommended dose.
The doctors consulted Louis Cantilena, a clinical pharmacologist at the hospital, who in turn called a
colleague at the U.S. Food and Drug Administration (FDA). Looking through FDA’s adverse events database,
FDA staffers found two dozen cases of arrhythmias from Seldane, or terfenadine—the majority in women.

It was one of the first red flags that researchers might have been missing sex differences in responses to drugs.
Combing through data on other medications, FDA and researchers realized that at least nine drugs could cause
potentially fatal heart arrhythmias in women, especially when prescribed with certain antibiotics. By 2001,
FDA had pulled four of these drugs off the market, including Seldane. “There’s no way to know how many,
but there were deaths,” says Raymond Woosley, then a pharmacologist at Georgetown University Medical
Center in Washington, D.C., who began studying the problem. The drug withdrawals fueled an argument
made by advocates for women’s health: Sex differences in responses to drugs had been missed because
women were not always included in clinical trials, or if they were, the data were not broken down by sex. That
has changed considerably in the past dozen years, after the National Institutes of Health brought more women
into clinical trials and FDA rescinded a 1977 rule that excluded women of childbearing age from early trials
(see p. 1570)—with positive results, advocates say. Earlier this year, for example, researchers reported in the
New England Journal of Medicine (NEJM) that aspirin—which protects
men against heart attack but not stroke—has exactly the opposite effect in women.

Yet sex differences in drug responses remain controversial. Concerns center on two aspects: how quickly
drugs are metabolized and absorbed, and how they affect the body once they’re in the bloodstream. Although
studies have found many differences in how women and men process drugs, these changes are less worrisome
than expected. Differences in how safe and effective a given blood level of a drug is for a man or woman are
probably bigger issues, many experts agree. This is harder to study, however, and so far only a few clear-cut
examples have emerged. That leaves some experts skeptical that sex will matter much in the long run; genetic
variation among individuals, especially of different ethnicity, may dominate, they say. “Gender is not the
major concern that we thought it would be,” says Leslie Benet, a pharmacologist at the University of
California, San Francisco (UCSF). But others counter that drug researchers have barely scratched the surface.
Despite prodding, clinicians still don’t always analyze data on women separately, and more research—and
better research tools—may yet reveal more serious gender differences, they say. Even subtle sex differences
may be important in an era of personalized medicine. “When it’s all done, we still find sex is a factor that
keeps coming out,” says clinical. pharmacologist and cardiologist Janice Schwartz of UCSF.

a) According to the text ; Gender in the Pharmacy: Does It Matter? Answer the question and give
examples from the reading .
b) How any drugs can cause heart arrhythmias in women?

c) Why the drug withdrawals fueled?