Women’s Drug Reactions Often Overlooked

Prescription drugs affect women differently than men. Their body composition is different, with more fat and less muscle, and they experience more dramatic hormonal changes, both of which play a crucial role in the body’s response to a drug.

Recognizing this, the Food and Drug Administration in 1998 required drug companies to test new medications on men and women. This more-thorough testing was supposed to better predict gender-specific side effects and correct common dosage problems.

Yet a recent congressional investigation found that the agency often fails to analyze the differences gender has on a drug’s safety and effectiveness. As a result, when new drugs are approved, the information women need about potential problems may not be available. Some women may even be endangering their lives by taking dosages that are too high or too low, or mixing medications that can cause adverse reactions.

The report, released in July by the General Accounting Office, said that, while women are now participating in pre-market trials, more than one-third of the drugs approved by the FDA from 1998 to 2000 did not have information on gender-related responses in their applications. The report found that not enough women were included in the early stages of drug tests, when safety and dosages for medications are established. The FDA agreed with the criticisms and is now implementing systems to correct these problems.

But in the meantime, “we’re still not getting the data we need to determine if drugs are safe and effective in women,” says Dr. Raymond Woosley, dean of the College of Medicine at the University of Arizona in Tucson. “Understanding women’s responses to medications is essential in order to make the best therapeutic decisions.”

For most medications, experts acknowledge, there isn’t a significant difference in how men and women handle a drug. “There haven’t been widespread problems that we know of yet,” says U.S. Rep. Henry Waxman (D-Los Angeles), one of the members of Congress who requested the GAO report. “But we should make these changes before there are.”

But with some drugs, gender can be a crucial factor. In fact, eight of 10 prescription drugs withdrawn from the market since January 1997 caused more adverse events in women than in men. Four of these drugs were used mostly by women; the other four were widely prescribed to men and women. There were 40 documented cases in which women were stricken with a condition known as Torsades de Pointes, an irregular heartbeat, which caused at least eight fatalities.

“These were all totally preventable deaths if we had only known,” says Woosley, who believes that monitoring women’s responses to these drugs might have picked up the cardiac arrythmias sooner. And it’s not just heart-related problems that pose risks. Gender plays a role in the cascade of physiological changes that occur when enzymes break down medications into their constituent chemicals. During this process, the chemicals are ferried through the bloodstream to the muscles and fatty tissues and then excreted through the kidneys. At each step, women respond differently than men.

For example, certain classes of drugs, such as benzodiazepines (Valium is one), have an affinity for fatty tissue. Consequently, they’ll remain in a woman’s body longer, which means she requires a lower dose than a man. Similarly, since women secrete less gastric acid, drugs aren’t absorbed as quickly in the intestinal tract, which also helps keep the drug in the system longer. Here again, women may need a smaller amount to get the same effect as men.

Age is a factor too--older women metabolize some drugs more slowly than younger women. And when a woman’s biochemical balance is disturbed--if she’s pregnant, taking birth control pills or on hormone replacement therapy--these variations are often even more pronounced.

Yet the GAO report found that women constituted only 22% of participants in the early phases of drug trials, when drugs are tested for toxicity and when effective dosages--how much and how often--are calibrated.

“We tried to find a one-size-fits-all approach for drugs because we want to keep it simple,” says Sherry A. Marts, scientific director for the Society for Women’s Health Research in Washington, D.C. “But keeping it simple means you overdose or underdose a lot of people. And women have mostly borne the brunt of that ignorance.”

The FDA halted drug tests on women of child-bearing age in the 1970s, after it was discovered that Thalidomide, a popular sleep aid in Europe, caused severe limb deformities in newborns. Gradually, “there was a spillover effect, and all women were excluded from drug tests,” says Susan F. Wood, director of the Office of Women’s Health at the FDA in Rockville, Md. The upshot was that for more than two decades, no one knew for sure what the correct drug treatment regimens were for half the population.

The FDA, however, is taking steps to rectify the situation, developing a demographic database that will collect gender-related information for drugs and medical devices. The agency also announced Friday that it will fund post-approval studies of certain medications on pregnant women. The first drugs to be studied will be the blood pressure medications labetalol and atenolol. Ultimately, the manufacturer will be able to specify a drug’s effects on pregnant women, something now largely unknown.

“Many women with chronic illnesses, like diabetes, hypertension, asthma, epilepsy and depression, require medication for their health,” Wood says. “We need to know if taking these drugs during pregnancy will harm the fetus.”

Other experts, however, say the FDA isn’t moving fast enough. “The agency needs to make this a priority,” says Marietta Anthony, director of Women’s Health Research at Georgetown University in Washington, D.C. “We need to know what happens afterward too, when the drugs are on the market.” Once millions are taking them, she points out, the potential for trouble increases exponentially.

In the meantime, women need to educate themselves, Anthony says. The next time you get a prescription filled, ask for the package insert for the medication.

* Find out if there are any known gender-related problems associated with the drug (check out these Web sites: https://www.torsades.org and https://www.PDR.net, for reactions to certain medications). If you don’t have Web access, ask your doctor or pharmacist.

* Alert your pharmacist or doctor if you’re taking oral contraceptives or hormone replacement therapy, both of which can affect a drug’s potency.

* Find out the warning signs of adverse drug reactions. Medication side effects run the gamut from headaches and nausea to tremors and seizures.

“Don’t dismiss symptoms like dizziness or indigestion,” Marts says. “Oftentimes, that’s an indication you’re taking too high a dose. If you experience problems, tell your doctor.”