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Previous Volume 349:535-545 August 7, 2003 Number 6 Next

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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.

Source Information

From the Atherosclerosis Research Unit, Keck School of Medicine (H.N.H., W.J.M., S.P.A., A.S., A.B.S., R.H.S.), the Department of Preventive Medicine (H.N.H., W.J.M., S.P.A., M.T.), the Department of Molecular Pharmacology and Toxicology, School of Pharmacy (H.N.H., A.S.), the Department of Obstetrics and Gynecology (D.S.), and the Division of Cardiovascular Medicine (H.N.H., A.O.M., R.R.), University of Southern California, Los Angeles; the Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York (R.A.L.); the Kaiser Permanente Medical Center, Los Angeles (P.R.M.); the Division of Cardiology, University of Chicago, Chicago (D.P.F.); Boston Heart Foundation, Boston (L.C.-H.); the Lakewood Regional Medical Center, Lakewood, Calif. (M.E.S.); the Division of Cardiology, Harbor–UCLA Medical Center, Torrance, Calif. (W.J.F.); Good Samaritan Hospital, Los Angeles (T.L.S.); Presbyterian Intercommunity Hospital, Whittier, Calif. (T.D.G.); Southern California Heart Specialists, Pasadena (K.H.V.); and the Jet Propulsion Laboratory, California Institute of Technology, Pasadena (R.H.S.).

Address reprint requests to Dr. Hodis at the Atherosclerosis Research Unit, 2250 Alcazar St., CSC132, Los Angeles, CA 90033, or at watcher{at}usc.edu.

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