Estrogen Therapy and Coronary Calcification

More evidence that estrogen therapy early in menopause may confer more benefit than risk

Findings from the Women’s Health Initiative (WHI) trial showed that taking conjugated equine estrogens did not reduce the risk for coronary events in postmenopausal women who had undergone hysterectomies. A subgroup analysis, however, suggested an age interaction, in which estrogen conferred a cardiovascular benefit on the younger subjects. To pursue this issue further, the WHI Coronary-Artery Calcium Study was designed to determine whether the younger women treated with estrogens had lower coronary-artery calcium scores than those treated with placebo. This substudy was restricted to women who were 50 to 59 years old at the time of randomization; follow-up scans were obtained an average of 8.7 years later.

Coronary-artery calcium scores were available for 1064 eligible participants. The mean scores were 83 in the estrogen group and 123 in the placebo group (P=0.02). The 50th percentile value of the scores was 0 in both groups, and the 75th percentile values were 43 in the estrogen group and 84 in the placebo group. The overall distribution of scores was significantly lower in the estrogen group than in the placebo group.

Comment: This WHI follow-up study provides additional evidence that estrogens may be beneficial for younger postmenopausal women. These results, however, should not be considered independent confirmation of the original subgroup analysis, because they were found in the same group of patients. Also, although coronary-artery calcium scores are predictive of outcomes, these findings do not translate directly to better outcomes with estrogen treatment, nor do they overturn current recommendations that hormone therapy be limited to the treatment of moderate-to-severe menopausal symptoms, using the lowest effective dose for the shortest duration necessary.

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology July 18, 2007

Citation(s):
Manson JE et al. for the WHI and WHI-CACS Investigators. Estrogen therapy and coronary-artery calcification. N Engl J Med 2007 Jun 21; 356:2591-602.