http://www.miami.com/mld/miamiherald/living/12903682.ht...l=miamiherald_living

Safety concerns mount; age could be a factor
Many questions still exist on the risks involved in taking hormones, even low-dose ones, over time.

BY JODI MAILANDER FARRELL
jmailander@herald.com

Nearly 40 years ago, New York gynecologist Robert Wilson published Feminine Forever, a book that fueled the popularity of estrogen, with warnings that women were doomed to become shriveled, sexless and sickly unless they took hormones.

The benefits of estrogen were backed up in the 1970s, when a huge study called the Nurses Health Study found that women who took hormones had lower rates of heart disease than women who did not.

The National Institutes of Health funded the more scientifically rigorous WHI to try to definitively answer the question. The WHI involved nearly 17,000 women between the ages of 50 to 79.

The Prempro arm of the study was halted in 2002 after researchers decided the risks of continuing were too great. Two years later, a trial of estrogen-only Premarin involving women who had hysterectomies was halted for the same reason.

For every 10,000 women taking Prempro, there were eight more cases of breast cancer, eight more women had strokes, seven more had a heart attack and 18 more had blood clots, compared with women taking a placebo, researchers found. The risk of breast cancer rose significantly after the fourth year, while the risk of cardiovascular problems increased immediately in the hormone group.

Earlier this year, an NIH panel reiterated to doctors and patients to use hormones sparingly, even in low-dose forms.

"Little is known about major adverse events that could be associated with three- to five-year exposure to low-dose estrogen and progestins," the panel said.

Yet two doctors from Harvard Medical School suggested in an opinion piece in Newsweek's Jan. 17 issue that age may make the crucial difference, which explains why both the NIH and Nurses Health Study could be correct.

Drs. Anthony L. Komaroff and Francine Grodstein believe that HT might decrease the risk of heart disease in relatively younger women by slowing the development of plaques known to cause heart attacks. At the same time, hormones could increase the risk in relatively older women who have already formed those plaques. The WHI showed that the risk of developing heart disease was clearly higher for women starting hormones many years after menopause than for women who did not take hormones.

"For every question the Women's Health Initiative answered, there are three more that it left or stimulated," says Diaz of Cleveland Clinic Florida. "But this can be good because the more questions we have, the more we'll learn."