Hormone Hazards

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m really looking forward to the year 2005. That's when a large clinical trial called the Women's Health Initiative (whi) should finally answer the question "Do the benefits of taking estrogen and progestin for years, even decades, after menopause outweigh any risks?" There has been lots of evidence over the years that the answer is yes and yet plenty of data that lean toward no. Just last week a report in the Journal of the American Medical Association said that taking estrogen for 10 years or more doubles a woman's risk of dying from ovarian cancer. Is it any wonder women are confused?

The WHI should pretty well settle the matter because it's a randomized, placebo-controlled trial, the most rigorous type of study researchers know how to design. More than 27,000 women, ages 50 and older, are taking either the drugs or a dummy pill for anywhere from eight to 12 years. Because neither they nor the medical staff running the program knows who is getting what, you can bet the results will be as objective as humanly possible.

Until then, whenever any new study--like the ovarian-cancer report--comes along, you have to consider it as part of the larger picture. The first thing you must realize, says Dr. Carmen Rodriguez, a senior epidemiologist at the American Cancer Society who led the study, is that a woman's chances of dying from ovarian cancer are pretty low--about 1.7% over the course of her lifetime. Twice a low risk is still a low risk. (Study participants who took estrogen actually lived longer than those who didn't--partly because such volunteers often live healthier lives and have better access to medical care.)

Next, keep in mind that the J.A.M.A. study was conducted at a time when most doctors still gave women estrogen by itself. Since then, women who haven't undergone a hysterectomy have generally received estrogen plus progestin because the combo reduces the risk of uterine cancer. It's quite possible taking both drugs reduces the risk of ovarian cancer as well.

Clearly, medical researchers are not as confident of the health benefits of long-term hormone therapy as they used to be. Investigators were surprised last year when preliminary evidence from the whi revealed that taking estrogen with or without progestin slightly increased the risk of blood clots, heart attacks and strokes over a two-year period. The researchers are waiting for the final results to see if the short-term risk is outweighed by any long-term protection for the heart.

Meanwhile, no one is denying that hormone therapy has some pretty powerful short-term benefits. "Estrogen is still the most effective treatment for hot flashes and perimenopausal symptoms," notes Dr. JoAnn Manson, chief of preventive medicine at Harvard's Brigham and Women's Hospital. Nor is there anything in the latest study to suggest that women should avoid taking hormones for a few years around menopause. However, as a practical matter, women who have a family history of ovarian cancer or have undergone a partial hysterectomy (ovaries still intact) may want to rethink their choices for long-term hormone replacement. The rest of us are just going to have to wait four years for more definitive answers.

For more on the Women's Health Initiative, visit www.nhlbi.nih.gov/whi/hrt.htm. You can e-mail Christine at gorman@time.com