Postmenopausal hormones and coronary artery disease: potential benefits and risks

Various secondary prevention trials, including the Women's Health Initiative (WHI0, assessing the effects of hormone therapy (HT) on coronary artery disease (CAD) showed no benefit, and a trend towards early harm. However, in the WHI trial, there was a significant trend for decreasing CAD with time. The observational arms of WHI for both estrogen and estrogen/progestin suggested results which were similar to the cardioprotective effects reported in earlier observational studies. Women in these observational trials initiated hormones at a younger age and were generally healthier than women in the randomized trials. Hypotheses have been generated to explain the phenomenon of early harm, based on the induction of plaque instability in the older woman with existent significant atherosclerosis. A report of over 7000 early postmenopausal women initiating prospective trials on hormonal use did not find any evidence suggesting early harm. In the estrogen-only arm of the WHI trial, an analysis of the 50-59-year-old age group showed a near statistical decrease in coronary events: 63 (0.36-1.08), and a statistically significant reduction in a global coronary score, 0.66 (0.45-0.96). In a pooled analysis of 23 randomized clinical trials of hormonal therapy, those women within 10 years of menopause had a significant reduction in coronary events, 0.68 (0.48-0.96). Recent publications from WHI have shown a significant trend for reduced CAD and total mortality in younger women, as well as a reduced coronary calcium score when estrogen alone was given. In that neither aspirin nor statins have been shown to afford a statistical primary benefit for reducing CAD, the benefit of estrogen remains an attractive yet unproven possibility for younger women. In conclusion, while it is clear that HT has no place in the treatment of older women with CAD, emerging evidence strongly suggests a possible coronary benefit in younger healthy women.