How Drugs Affect the Sexes

Hormone replacement therapy may not be the only medication that is potentially dangerous to women. More evidence is showing that a host of prescription drugs may have differing side effects in women compared with men.

Unfortunately, that information only came to light recently, after researchers studied the life-threatening side effects of 10 drugs pulled off the market since 1997. Eight of the 10 medications, including the allergy drug Seldane and the acid reflux drug Propulsid, put women at more risk of side effects than men.

"A bunch of these drugs were found to be toxic," recalls Raymond D. Woosley, MD, PhD, vice president of the Arizona Health Sciences Center at the University of Arizona in Tucson. Woosley said researchers gradually came to see that the cases of side effects they were seeing were largely [occurring in] women, even though 10 times as many men were taking the drugs.

Armed with this information, Woosley went to the FDA, which is charged with making sure drugs are both effective and have an acceptable level of side effects, and to the National Institutes of Health. But, he says, no one was too concerned until the General Accounting Office, Congress's watchdog agency, responded to a request from Congress and looked at drugs withdrawn since 1997 (the Infamous Ten) to see which ones had a greater adverse effect on women than men.

Although the GAO said there might have been more side effects in some because more women than men took them (for example, fen-phen), four clearly affected women more: Posicor, Seldane, Hismanal, and Propulsid.

Comparing Side Effects by Sex

Of course, these drugs are now off the market, but what is being done to ensure that drugs affecting one gender over another are identified and doctors informed? This opens a whole new area: gender-based medicine. Until 1972, women of child-bearing age were not even allowed to participate in clinical trials of medications. Now, although women are included, the side effects that emerge are not always separated out by sex to see which might be occurring more often in women.

It would help to know if large numbers of side effects of medications are clustering in women, Woosley says. But the FDA does not tease that information out of the reports that come in, and only about one in 10 problems is ever reported anyway (it's voluntary).

"There is very little good data out there," confirms Lee Cohen, MD, associate professor of psychiatry at Yale and head of the Center for Women's Mental Health at Massachusetts General Hospital in Boston. "The FDA has mandated more attention to gender differences, but studies are not designed specifically to look at gender differences."

Understanding the Differences

There is now some evidence, according to Woosley, that it's not estrogen that makes women more sensitive to some drugs, but androgens possessed by the male that makes men less sensitive. Of course, reproductive hormones in women also exert an effect. Many drugs achieve different blood levels and effectiveness depending on when during a menstrual cycle they are taken. To make things more confusing, some drugs work differently in postmenopausal women than in premenopausal women. In the case of one drug, blood levels are lower during menstruation -- but the drug is actually more effective.

According to Cohen, women metabolize drugs differently in their livers than men. Reproductive hormones also control the time the medicine spends in the gut and the metabolic processes that break it down. The difference in women's muscle-to-fat ratio is also a factor. "Some medications can get sequestered (caught) in fat [changing their effectiveness and increasing side effects]," he explains.

How about genetics? "We can check for that (somewhat ) now," Woosley says. "We can swab a person's cheek, sequence the DNA, and see whether the drug is likely to cause a heart arrhythmia." This does not apply to all drugs, of course. At least, not yet.

What to Do For Now

Are doctors in possession of all this knowledge when they pull out the prescription pad? The answer is no. Of the 10 drugs withdrawn, only two carried a warning about effects on women.

Even in the absence of the recent brouhaha over hormone replacement, women should be careful about the medications they agree to take. Research, ask questions. Find out what the drug is supposed to do, how long you are to take it, whether it will interact with anything else you're taking, if you will need blood tests to check for absorption or damage to organs, and potential side effects. And, if course, never take another person's medication -- especially if that person is of the opposite sex!