Studies confirm adverse effects of combination HRT: more WHI data: estrogen-only formulations also implicated in breast ca, worsening of atherosclerosis.

For anyone who held out some hope that the Women's Health Initiative would show that combination hormone replacement therapy isn't so bad in certain subgroups of women, that hope is fading fast.

Results from two recent studies in the New England Journal of Medicine and one in the Lancet have mounted yet more evidence suggesting that combination estrogen and progestin is bad for a postmenopausal woman's heart and breasts.

In the first study, results from the final analysis of the estrogen plus progestin trial of the Women's Health Initiative (WHI) make one thing clear: estrogen plus progestin does not protect the heart. In fact, the combination may increase the risk of coronary heart disease among generally healthy post-menopausal women, especially in the first year after starting hormone replacement therapy.

"Hormone therapy should not be used to prevent or treat cardiovascular disease," Dr. Andrew Kaunitz, professor and assistant chair of the department of obstetrics and gynecology at the University of Florida Health Science Center in Jacksonville, told this newspaper. "That's a very clear message, and I don't think that point should be controversial anymore."

The study, which is an analysis of data from the WHI, found that the risk for CHD rose 81% among women who took Prempro, the conjugated estrogen/medroxyprogesterone acetate tablets manufactured by Wyeth Pharmaceuticals, compared with those who took placebo. The risk subsided over time, but at 5 years the risk for CHD still hovered around 24%. That translates to six more cases of CHD per year among every 10,000 women using estrogen plus progestin (N. Engl. J. Med. 349[6]:523-34, 2003).

Although he was not involved in this analysis, Dr. Kaunitz directs the WHI at the University of Florida. The question of whether to commence HRT "is all about the [woman's postmenopausal] symptoms," he said. "For well-informed patients, use of hormone therapy to effectively treat hot flashes and other vasomotor symptoms remains appropriate care. But given our evolving knowledge regarding risks, over time women on a serial basis need to be given an opportunity and encouraged to go off HRT and see if symptoms return or not. If they don't return, women should stay off of HRT. If the symptoms do return, many patients in my practice will choose to restart HRT, either at their former dose or perhaps at a lower dose."

In a prepared statement, Dr. Victoria Kusiak, North American medical director for Wyeth, supported this notion and recommended that hormone therapy "be used at the lowest dose for the shortest duration consistent with treatment goals and risks for the individual woman."