Hormone Therapy and the Progression of Coronary-Artery Atherosclerosis in Postmenopausal Women

The New England Journal of Medicine Volume 349:535-545  August 7, 2003  Number 6

Hormone Therapy and the Progression of Coronary-Artery Atherosclerosis in Postmenopausal Women

Howard N. Hodis, M.D., Wendy J. Mack, Ph.D., Stanley P. Azen, Ph.D., Roger A. Lobo, M.D., Donna Shoupe, M.D., Peter R. Mahrer, M.D., David P. Faxon, M.D., Linda Cashin-Hemphill, M.D., Miguel E. Sanmarco, M.D., William J. French, M.D., Thomas L. Shook, M.D., Thomas D. Gaarder, M.D., Anilkumar O. Mehra, M.D., Ramin Rabbani, M.D., Alex Sevanian, Ph.D., Asit B. Shil, M.D., Mina Torres, M.S., K. Heiner Vogelbach, M.D., Robert H. Selzer, M.S., for the Women's Estrogen–Progestin Lipid-Lowering Hormone Atherosclerosis Regression Trial Research Group

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ABSTRACT

Background In postmenopausal women with coronary artery disease, conjugated equine estrogen with or without continuous administration of medroxyprogesterone acetate has failed to slow the progression of atherosclerosis. Whether 17-estradiol (the endogenous estrogen molecule) alone or administered sequentially with medroxyprogesterone acetate can slow the progression of atherosclerosis is unknown.

Methods We conducted a double-blind, placebo-controlled trial in 226 postmenopausal women (mean age, 63.5 years) who had at least one coronary-artery lesion. Participants were randomly assigned to usual care (control group), estrogen therapy with micronized 17-estradiol alone (estrogen group), or 17-estradiol plus sequentially administered medroxyprogesterone acetate (estrogen–progestin group). In all patients the low-density lipoprotein (LDL) cholesterol level was reduced to a target of less than 130 mg per deciliter. The primary outcome was the average per-participant change between base-line and follow-up coronary angiograms in the percent stenosis measured by quantitative coronary angiography.

Results After a median of 3.3 years of follow-up, the mean (±SE) change in the percent stenosis in the 169 participants who had a pair of matched angiograms was 1.89±0.78 percentage points in the control group, 2.18±0.76 in the estrogen group, and 1.24±0.80 in the estrogen–progestin group (P=0.66 for the comparison among the three groups). The mean difference in the percent stenosis between the estrogen group and the control group was 0.29 percentage point (95 percent confidence interval, –1.88 to 2.46), and the mean difference between the estrogen–progestin group and the control group was –0.65 (95 percent confidence interval, –2.87 to 1.57).

Conclusions In older postmenopausal women with established coronary-artery atherosclerosis, 17-estradiol either alone or with sequentially administered medroxyprogesterone acetate had no significant effect on the progression of atherosclerosis.