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date: 2/8/2006
Drug safety: His and hers
Medications that are good for the goose can be bad for the gander—and vice versa. Here's what you need to know.
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Even when treatment should be identical, research shows that women and men often receive very different care for the same health problems. Men who suffer broken bones because of osteoporosis, for example, are less likely than women to receive appropriate treatment with bone-building drugs, such as alendronate (Fosamax) and risedronate (Actonel). And doctors prescribe heart-protecting beta-blockers and cholesterol-lowering statins to men with a history of heart disease more often than they do to women in the same situation, though research suggests women need those medications just as much as men.

Even less attention is given to the fact that the same drug can affect men and women in very different ways, resulting in different risks, effectiveness levels, or both. Some drugs used for treating high blood pressure, for example, can ease a common urinary problem in men but trigger or worsen a urinary problem more often found in women. And the anti-allergy drug terfenadine (Seldane) was taken off the market by the U.S. Food and Drug Administration in 1998 when it became clear that the medication was more likely to cause potentially deadly heartbeat abnormalities in women than in men.

Here is a guide to why men and women respond to many drugs differently. These include common ones such as low-dose aspirin used to prevent heart attacks, various painkillers, and antidepressants. Learn how those differencesaffect which drugs and dosages you should, and shouldn't, take.
Medication tips

HIS
  • Make sure that the starting dose of a new medication—especially an antidepressant—is adequately relieving your symptoms, and consider asking your doctor about boosting the dosage or switching drugs if symptoms persist.
  • Consider taking lower doses of nonsteroidal anti-inflammatory drugs such as ibuprofen (Advil, Motrin) if they adequately control your pain and inflammation.
  • Talk to your doctor about starting low-dose aspirin therapy after age 40, even if you are only at a moderately elevated risk of heart attack.
HERS
  • Ask your doctor about starting medications at lower-than-usual starting dosages, since you may be more sensitive to drug side effects.
  • Before surgery, discuss pain relief with your doctor and the possibility that you may need extra medication during and after the operation to control pain.
  • Consider low-dose aspirin therapy starting at about age 45 only if you are at very high risk of heart attack or ischemic stroke; otherwise, you should consider the therapy starting at age 65.
GENDER AND METABOLISM

Historically, drug companies tested new medicines mainly in men. Scientists assumed that drug effects were roughly comparable in women and wanted to avoid complicating the studies with concerns about female menstrual cycles and pregnancies. In 1998, however, the FDA required that clinical trials not only include women but specifically report on a drug's safety and efficacy in women as well as men.

Such research has yielded important insights into basic differences between how male and female bodies process medications. And while body size and sex hormones contribute to those variations, they don't explain them all. "We've identified some basic differences that may affect how men and women absorb drugs into the bloodstream, distribute them to the body's tissues, break them down, and get rid of them," says Marianne Legato, M.D., a cardiologist and founder of the Partnership for Gender-Specific Medicine at Columbia University. For example, differences in stomach acidity and gastric-emptying rate may affect how quickly drugs dissolve and enter the bloodstream. One FDA analysis of such research identified significant gender-related differences with about 20 percent of nearly 200 medications.

Those differences may influence the optimal dosage of a medication for men and women, an issue worth discussing with your physician. However, it's important to never change medication doses on your own.
WOMEN: CONSIDER LOWER DOSES?

In general, metabolic differences tend to make women more sensitive to medication. And since most drugs on the market haven't been tested extensively in women, the recommended starting dosages are often too high for them. So it makes sense for women—as well as individuals who are older, thinner, or smaller—to ask their doctor whether it might be safer to start a new medication with a lower-than-usual dose.

If you do start low, be sure your doctor monitors your progress during the first weeks or months to check whether the drug is working and to possibly increase the dose if it's not.
MEN: CONSIDER HIGHER ONES?

On the other hand, starting dosages are more likely to be too low for men, especially larger men taking relatively new medications that were initially tested in mixed-gender trials. Such men shouldn't start with higher-than-usual doses, but they should make sure that their doctor monitors their condition and increases the dosage, or switches drugs, if necessary.

One notable example: depression. Research suggests that men may not benefit as much as women from new antidepressant medications-including selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs), such as fluoxetine (Prozac), paroxetine (Paxil), and venlafaxine (Effexor). That may be partly because of differences in brain chemistry, since depressed women tend to have less serotonin, a key mood-moderating brain chemical, than depressed men do.

"But it could simply be that the dosages of those new drugs are often too low for men," says Arif Khan, M.D., of the Northwest Clinical Research Center in Bellevue, Wash. If standard antidepressant dosages don't work, men should talk with their doctor about boosting the dose or switching to older, tricyclic antidepressants, such as amitriptyline (Elavil), imipramine (Tofranil), and nortriptyline (Aventyl, Pamelor), all available in generic versions. Those drugs may ease depression in men somewhat better than the newer ones do, though they usually cause more side effects.
PAIN-RELIEF EXCEPTION

Pain medications are among the exceptions to the general rule that women are more sensitive to medication than men. Research shows that men tend to have higher pain tolerances than women, and may also experience greater relief from drugs used to manage pain.

That's especially true during and after surgery. Studies suggest that women are more likely than men to report some awareness during an operation, and thus may require a larger dose of anesthesia. Women are also more likely than men to wake up soon after surgery and to experience significant pain as they recover. So it's especially important for women to have a discussion with their doctor before surgery about receiving adequate and appropriate medication before and after the operation.

Other studies hint that the anti-inflammatory effect of drugs such as ibuprofen (Advil, Motrin) is greater in men than in women. Moreover, women tend to have a greater inflammatory response to triggers such as infections. So men may get by with lower dosages than women when treating inflammation-related pain.
Preventive aspirin for men and women?

National guidelines say that most middle-aged and older men and women should consider daily low-dose aspirin (81 mg) if they are at moderately elevated coronary risk. But results from a huge Harvard University trial published in March 2005 suggest that aspirin offers different benefits to men and women.
  • Men: In both genders, aspirin increases the chance of gastrointestinal bleeding. But in men with increased coronary risk over 40, that risk is generally outweighed by aspirin's substantial ability to cut the risk of having a first heart attack.

    Men over 40 should assess their heart-attack risk using the risk calculator at www.med-decisions.com. They should consider low-dose aspirin therapy if that calculator shows that they have a 3 percent or greater risk of heart attack or death from coronary disease in the next five years and their doctor says they aren't at high risk of gastrointestinal bleeding.
  • Women: The recent Harvard study found that while aspirin does slightly lower the risk of ischemic, or clot-related, stroke in women starting at age 45 (a benefit not seen in men), it offers no heart-attack protection for them until they reach age 65. Overall, aspirin's benefit for most women—against ischemic stroke and heart attack—doesn't appear to outweigh the risk of gastrointestinal bleeding until they reach age 65.

    Women 45 and older should determine not only their heart-attack but also their stroke risk using the calculator at www.nhlbi.nih.gov/about/framingham/stroke.htm. Women over 65 at normal gastrointestinal risk should consider aspirin therapy if they're at high risk of ischemic stroke or if their five-year heart-attack risk is 3 percent or higher. Younger women generally don't need aspirin therapy unless they have an unusually high risk of heart attack or ischemic stroke.
  • Men and women: If you're taking low-dose aspirin, don't stop without first talking to your doctor. Abrupt stopping may increase your risk of a heart attack. If a high gastrointestinal risk prevents you from taking aspirin, ask your doctor whether a different blood-thinning medication would be appropriate.

CITATIONS
Evelyn B, et al. “Women’s participation in clinical trials and gender-related labeling: A review of New Molecular entities approved 1995-1999,” June 2001, FDA Center for Drug Evaluation and Research.

Khan A, et al. “Sex differences in antidepressant response in recent antidepressant clinical trials,” Journal of Clinical Psychopharmacology, August 2005, pp. 318-24.
Hildebrandt MG, et al. “Are gender differences important for the clinical effects of antidepressants?” American Journal of Psychiatry, September 2003, pp. 1643-50.

Aubrun F, et al. “Sex and age related differences in morphine requirements for postoperative pain relief,” Anesthesiology, July 2005, pp.156-60.

Sycha T, et al. “A simple pain model for the evaluation of analgesic effects of NSAIDs in healthy subjects,” British Journal of Clinical Pharmacology, August 2003, pp. 165-72.

Ridker PM, et al. “A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women,” The New England Journal of Medicine, March 31, 2005, pp. 1293-1304.

OTHER SOURCES
Keogh E, McCracken LM, Eccleston C. “Do men and women differ in their response to interdisciplinary chronic pain management?” Pain, March 2005, pp. 37-46.

Donovan MD. “Sex and racial differences in pharmacological response: Effect of route of administration and drug delivery system on pharmacokinetics,” Journal of Women’s Health, January-February 2005, pp. 30-7.

Anderson GD. “Sex and racial differences in pharmacological response: Where is the evidence? Pharmacogenetics, pharmacokinetics, and pharmacodynamics,” Journal of Women’s Health, January-February 2005, pp. 19-29.

Gandhi M, et al. “Sex differences in pharmacokinetics and pharmacodynamics,” Annual Review of Pharmacology and Toxicology, 2004, pp. 499-523.

Tecce MA, Dasgupta I, Doherty JU. “Heart disease in older women: Gender differences affect diagnosis and treatment,” Geriatrics, December 2003, pp. 33-9.

Cohen JS. “Do standard doses of frequently prescribed drugs cause preventable adverse effects in women?” Journal of the American Medical Women’s Association, Spring 2002, pp. 105-10.

U.S. Preventive Services Task Force. “Aspirin for the primary prevention of cardiovascular events: Recommendation and rationale,” Annals of Internal Medicine, January 15, 2002, pp. 157-60.


This article originally appeared in the December 2005 issue of Consumer Reports on Health.


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