Estrogen safety: studies raise cancer, blood clot questions.

Three studies this week brought mixed news about the risks of estrogen-only hormone replacement therapy to ameliorate menopausal symptoms.

Data from a massive study called the Women's Health Initiative (WHI) show that estrogen therapy taken for 7 years doesn't increase a woman's risk of breast cancer. However, a separate study of black women finds a greater risk of breast cancer in women who took the hormone for 10 or more years than in women who had no hormone therapy.

What's more, another analysis of the WHI data reveals that women taking estrogen were more likely to develop blood clots than were women getting dummy pills.

Researchers launched the WHI in part to study the long-term effects of hormone replacement. However, the estrogen-only study was stopped in 2004 after researchers noted an increased incidence of stroke among women taking the hormone. That boost in stroke risk, combined with the new results, suggests that estrogen's declining reputation isn't likely to rebound any time soon, says J. David Curb, a geriatrician at the University of Hawaii in Honolulu, who coauthored the blood clot study.

"The best answer we have is that estrogens are probably not beneficial for post-menopausal women,' says Curb.

The WHI cancer study enrolled post-menopausal women who had had hysterectomies. Roughly half of the 10,739 women participating took estrogen, and the other half took a placebo. The new analysis finds no significant difference in the rates of breast cancer in the two groups after 7 years, scientists report in the April 12 Journal of the American Medical Association.

In the other cancer study, epidemiologist Lynn Rosenberg of Boston University and her colleagues analyzed estrogen use and breast cancer risk among 23,000 black women. Women who had taken estrogen for 10 or more years had a 41 percent greater rate of breast cancer than did women who had never taken the hormone, the researchers report in the April 10 Archives of Internal Medicine. The difference in the results of the two studies may arise from the shorter average follow-up of WHI, Rosenberg says.

"There's a huge amount of evidence that estrogen is related to the risk of breast cancer in women;' Rosenberg says.

However, the hormones used in prescriptions aren't identical to human estrogen, so although the natural hormone can promote breast cancer, it's difficult to know whether the drug does, says Marcia L. Stefanick, a Stanford University physiologist who coauthored the WHI breast cancer study.

In the other WHI analysis, 0.30 percent of women receiving estrogen, but only 0.22 percent of those getting a placebo, developed blood clots large enough to block a vein, Curb and his colleagues report in the Archives issue.

Doctors should prescribe estrogen only for women "with menopausal symptoms that are intolerable," Stefanick says.