Effects of estrogen replacement with and without medroxyprogesterone acetate on brachial flow-mediated vasodilator responses in postmenopausal women with coronary artery disease

Background Hormone therapy has been shown to have no cardioprotective effect and may, in fact, be harmful in older postmenopausal women. Estrogen has been shown to enhance endothelial-dependent flow-mediated vasodilation (FMD) in healthy and younger women. The effect of estrogen on older and less healthy postmenopausal women with atherosclerosis is unclear. Methods The Estrogen Replacement and Atherosclerosis trial randomized 309 postmenopausal women with established coronary atherosclerosis (mean, 65.8 years) to unopposed estrogen (conjugated estrogen, 0.625 mg), estrogen plus 2.5 mg medroxyprogesterone actate (MPA), or placebo. After mean of 3.2 years of follow-up, brachial FMD was measured using 2-dimensional ultrasound in women available for follow-up at 4 of the 5 clinic sites (n = 198). Results The %FMD of the brachial artery was not statistically different in the placebo arm compared with either unopposed estrogen or estrogen + MPA arm in both the adjusted and the unadjusted models. Subsequent analysis combining the estrogen arm with the estrogen + MPA arm and comparing with the placebo arm was also not significant in both the adjusted and the unadjusted models. Similar results were obtained when analyses were limited to women who took >80% of the study medication over the course of the trial (n = 133). Conclusion An average of 3.2 years of treatment with unopposed estrogen or estrogen plus progestins did not result in significant improvements in endothelial vasodilation compared with placebo. This apparent absence of an effect on brachial artery endothelial function in older postmenopausal women with established coronary heart disease may help explain the lack of benefit of estrogen for secondary prevention of coronary heart disease.