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In brief: Hormone therapy heart benefit may depend on timing

In brief

Hormone therapy heart benefit may depend on timing

A study suggests that hormone therapy may be good for the heart after all — but only if it's initiated during a fairly narrow window of opportunity. Researchers at the Harvard Medical School analyzed data from the Nurses' Health Study, which has followed more than 120,000 female nurses since 1976. They found that women who started hormone therapy within about four years of menopause had a risk for heart disease nearly 30% lower than that of women who never used hormones. On the other hand, beginning hormone therapy 10 or more years after menopause or after age 60 showed little if any benefit. The findings were published in the January/February 2006 issue of the Journal of Women's Health.

The Harvard study, co-authored by Dr. JoAnn Manson, was undertaken to shed light on apparent discrepancies between earlier studies linking postmenopausal hormones with a reduced risk for heart disease and results from the Women's Health Initiative (WHI), which tested both an estrogen and progestin combination (Prempro) and estrogen alone (Premarin) against a placebo. The Prempro trial was halted in 2002 when it became clear that hormone users were experiencing more heart disease, stroke, and blood clots than the women taking the placebo pill. The estrogen-only trial also ended early, in 2004, because Premarin increased participants' risk for stroke without conferring any benefits for heart health.

These unanticipated findings led to considerable confusion and a sea change in clinical practice. Once widely prescribed long-term because it was thought to stave off heart problems and other age-related illnesses, hormone therapy was quickly relegated to strictly short-term treatment of symptoms such as hot flashes and vaginal dryness.

Several questions arose in the wake of the WHI's landmark effort to ascertain hormone therapy's role in disease prevention. A chief criticism was that the WHI tested hormone therapy in women who were mostly in their 60s and 70s, whose arteries may already have had the beginnings of heart disease (atherosclerosis). However, outside of studies, women usually begin taking hormone therapy in their late 40s or early 50s to treat menopausal symptoms. WHI participants who were younger at the start of the study may have fared better. Analysis of the data continues, and we should know more about that soon.

In the meantime, the findings from the Nurses' Health Study suggest that starting hormone therapy earlier may indeed make a difference. But Dr. Manson and her colleagues emphasize that many questions remain, especially about the safety of long-term hormone use in younger women: "More research is needed to confirm this apparent association and to improve our understanding of the benefits and risks of hormone therapy when started early after menopause," says Dr. Manson. "Fortunately," adds gynecologist Dr. Martha K. Richardson, "there are many other drugs and lifestyle options for preventing heart disease in women."

Studies are already under way to find out more about hormone therapy. The Kronos Early Estrogen Prevention Study (KEEPS) is testing whether starting hormone therapy six months to three years after the last menstrual period will prevent the progression of atherosclerosis. The trial will also test two different types of hormone preparations at low doses. Dr. Manson is a principal investigator with KEEPS. Another study, the Early versus Late Intervention Trial with Estradiol (ELITE), funded by the National Institutes of Health, will compare the effects of estrogen (estradiol) started in early menopause with estrogen begun 10 or more years after menopause.

Last updated:	September 05, 2008