By Rebekah McCallister

Standard-dose oral conjugated estrogen therapy is associated with a significant reduction in calcified plaque in the coronary arteries and appears to be safe when started during early menopause, according to new data from an ancillary substudy (N Engl J Med. 2007;356:2591-2602) of the Women's Health Initiative (WHI).

"In the 5 years since the WHI study ended, new data have emerged that help put the initial findings into perspective. These results showed that in these younger menopausal women, estrogen therapy reduced calcified plaque buildup in the arteries," commented Howard Hodis, MD, professor of medicine and preventive medicine and director, Atherosclerosis Research Unit, University of Southern California. "These data support initiation of estrogen therapy, where indicated, when a woman first enters menopause and begins experiencing symptoms of bone loss."

JoAnn E. Manson, MD, DrPH

What should you advise your patients who are concerned about the WHI results? "Recent studies provide some reassurance for recently menopausal women who are considering hormone therapy for the short-term management of moderate-to-severe hot flashes and night sweats," lead investigator JoAnn E. Manson, MD, DrPH, of Brigham and Women's Hospital, Boston, who was also one of the principal investigators of the WHI, told IMWR.

In this ancillary substudy of the WHI study, 1064 women (aged 50-59 years) who had undergone hysterectomy were randomized to receive conjugated equine estrogen (0.625 mg/d) or placebo for a mean of 7.4 years. Computed tomography scans of the heart were obtained in all the women.

At an average of 8 years after randomization, the prevalence of coronary artery calcification was significantly lower in the estrogen group than in the placebo group. Specifically, the odds ratio for increased coronary artery calcium was from 30% to 40% lower in the intention-to-treat analyses and 60% lower among women who were at least 80% adherent with the study treatment for ≥5 years.

Overall, mean coronary artery calcium score was significantly lower among women in the estrogen group than among those in the placebo group.

"The evidence is mounting that a woman's age and amount of time since menopause influence her health outcomes on estrogen, particularly her risk of heart disease. [These] findings lend support to the theory that estrogen may slow early stages of atherosclerosis. However, due to other possible risks, hormone therapy should not be started (or continued) for the express purpose of preventing cardiovascular disease in either younger or older postmenopausal women," said Dr Manson.

These findings are consistent with another recent reanalysis of pooled estrogen-alone and estrogen-plus-progestin data from the WHI study (JAMA. 2007;297:1465-1477). The investigators reported no apparent increase in coronary artery disease for women who started hormone therapy within 10 years of menopause.

"Estrogen remains a viable treatment option for recently menopausal women who have moderate-to-severe vasomotor symptoms," Dr Manson stated. "Current guidelines that hormone therapy be limited to symptom management, using the lowest effective dose for the shortest duration necessary, remain appropriate," she said.

The effect of estrogen on the development of atherosclerosis in recently menopausal women is also being studied in the Kronos Early Estrogen Prevention Study (KEEPS), which is comparing low doses of oral versus transdermal estrogen for the prevention of blood vessel narrowing.