BOSTON, June 20 -- Estrogen reduced coronary calcium in women younger than 60 who took the hormone following a hysterectomy, researchers reported here.But the findings should not be construed as evidence that estrogen should be routinely used to reduce the risk of heart disease in older women, said JoAnn E. Manson, M.D., Dr. P.H., of Brigham and Women's Hospital and Harvard.Women ages 50 to 59 who took 0.625 mg of conjugated equine estrogen daily (Premarin) had a mean coronary calcium score of 83.1 versus 123.1 (P=0.002 by rank test), wrote Dr. Manson and colleagues in the June 21 issue of the New England Journal of Medicine.
Coronary artery calcium scores of 101 to 300 are considered moderate calcification and scores of more than 300 are considered extensive calcification.
The Women's Health Initiative (WHI) findings should be considered reassuring for women who are using estrogen for control of moderate to severe menopause symptoms, she said, but added, "this is no way changes the findings that the risk of hormone therapy outweighs the benefit." Breast cancer, strokes, and deep vein thrombosis are a few of the risks associated with hormone therapy, she and colleagues noted.
The women in this trial were enrolled in the WHI-Coronary Artery Calcium Study, a spin-off trial from the landmark WHI study. That National Heart, Lung, and Blood Institute trial of more than 27,000 women was halted in July 2003 when it was determined that the risks of hormone therapy with estrogen and progestin (Prempro) outweighed its benefits.
The estrogen-only arm of WHI randomized 10,739 women who had undergone hysterectomy to estrogen or placebo. Women were treated for a mean of 7.4 years and an earlier analysis of that data suggested that estrogen reduced the risk of cardiovascular events in younger women.
"This study is a follow-up that attempted to determine the mechanism of that apparent benefit," Dr. Manson said.
About a tenth of the original estrogen only cohort (1,064 women) underwent CT scans 1.3 years after the original trial was completed. Imaging was conducted at 28 of the 40 centers that participated in the WHI estrogen study.
Among the findings:
Women who were at least 80% adherent to estrogen therapy reduced their risk of having a calcium score of 100 or higher by 54% (P=0.001).
By intention-to-treat analysis, women randomized to estrogen reduced their risk of high levels of coronary artery calcium (scores of 300 or more) by 30% to 40%, and women who took estrogen more than five days a week reduced their risk of high levels of coronary calcium by 60%.
In an NEJM editorial that accompanied the study, Michael E. Mendelsohn, M.D., and Richard H. Karas, M.D., Ph.D., of Tufts-New England Medical Center, wrote that women and physicians should be reassured by the WHI-CACS results.
The study by Dr. Manson and colleagues "and other recent studies support the hypothesis that estrogen can reduce the risk of coronary heart disease in women 50 to 59 years old, which should help clarify this confusion," they wrote.
They also cautioned that "hormone-replacement should not be considered as a strategy to prevent cardiovascular disease in women."
Howard Hodis, M.D. Univ. Southern California
They pointed out that the study supports the concept that "estrogen therapy is unlikely to have an adverse effect on the risk of coronary events among women who have recently undergone menopause and are considering hormone therapy for the treatment of menopausal symptoms."
Despite those cautions, the response from those favoring HRT was quick. For example, Howard Hodis, M.D., of the University of Southern California, said at a media briefing that the data support the use of estrogen to reduce the risk of heart disease in younger women.
That kind of reaction is a researcher's worst nightmare, said Marcia L. Stefanick, Ph.D., of Stanford University, also a WHI-CACS investigator.
Dr. Stefanick
Dr. Stefanick said it was a mistake to attempt to generalize the latest findings because "this was a very select, very different population. They had surgical menopause -- often years before they entered the trial -- they were younger than the overall population of menopausal women, there were more minorities, their were more obese women, and they were willing to enter a trial in which they might or might not receive hormones. These are not your average middle-age women."
Moreover, she cautioned about a little discussed side effect of hormone therapy. Once women started taking estrogen, they found it difficult to stop. "Clinicians need to realize that when they start women on these drugs they may have difficulty getting them off," she said.
WHI-CACS was supported by NHLBI, study pills were supplied by Wyeth Pharmaceuticals. Drs. Manson, Stefanick, Mendelsohn, and Karas declared no conflicts. Dr. Hodis said he is a consultant for Wyeth Pharmaceuticals the maker of both Premarin and Prempro.Primary source: New England Journal of MedicineSource reference: Manson JE et al "Estrogen Therapy and Coronary-Artery Calcification" N Engl J Med 2007; 356:2591-602. Additional source: New England Journal of MedicineSource reference: Mendelsohn ME and Karas RH "HRT and the Young at Heart" N Engl J Med 2007; 356:2639-2641.
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