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Risks Remain for Hormone Replacement Therapy

Hopes for risk-free hormone replacement therapy for menopause have dimmed with a report that a regimen thought to reduce its dangers does not offer complete protection. For decades, women have taken estrogen to relieve some of the discomforts of menopause--and more recently, to lower their risk of heart disease and osteoporosis. The therapy raises the risk of endometrial cancer, however--a risk that combining estrogen with another hormone, progestogen, was thought to reduce. But in the 15 February issue of The Lancet, researchers report that the benefits of progestogen appear primarily in women who take the hormone more than 10 days per month, and even then may not fully protect very long-term users.

Epidemiologist Shirley Beresford and her colleagues at the University of Washington interviewed 832 endometrial cancer patients and 1114 randomly chosen, healthy controls about their use of hormone replacement therapy. All the women were between the ages of 45 and 74. From their data, the authors estimate that for women who take only estrogen, the annual risk of developing endometrial cancer is four in 1000. For women who took progestogen fewer than 10 days per month, the risk was only slightly less--three in 1000. Only women who took progestogen more than 10 days per month had the same cancer risk as women who took no hormones--about one in 1000. The results, which agree with earlier, smaller studies, "make the strong suggestion that adding progestogen only a few days per month does not protect from endometrial cancer," Beresford says.

But when the team looked at the small subset of women who had taken hormone replacement therapy for more than 5 years, they were surprised to find an increased risk of endometrial cancer even for those who took progestogen more than 10 days per month. The results are preliminary but provocative, says epidemiologist Louise Brinton of the National Cancer Institute. "There is a dogma out there that progestogen eliminates all risk," she says, "but there are a lot of unanswered questions" about combination therapy.

Even with the possible long-term risk, says University of Southern California gynecologist Daniel Mishell, endometrial cancer is uncommon and, when associated with estrogen use, is almost always curable. Given the "marked benefit in cardiovascular disease and osteoporosis," he says, the latest findings "should not dissuade women ... from taking estrogen."