Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women.
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 17beta-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 17beta-estradiol alone (estrogen group), or 17beta-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, 17beta-estradiol either alone or with sequentially administered medroxyprogesterone acetate had no significant effect on the progression of atherosclerosis.
Hodis
Howard N
HN
Atherosclerosis Research Unit, Keck School of Medicine, Los Angeles, CA 90033, USA. watcher@usc.edu
Mack
Wendy J
WJ
Azen
Stanley P
SP
Lobo
Roger A
RA
Shoupe
Donna
D
Mahrer
Peter R
PR
Faxon
David P
DP
Cashin-Hemphill
Linda
L
Sanmarco
Miguel E
ME
French
William J
WJ
Shook
Thomas L
TL
Gaarder
Thomas D
TD
Mehra
Anilkumar O
AO
Rabbani
Ramin
R
Sevanian
Alex
A
Shil
Asit B
AB
Torres
Mina
M
Vogelbach
K Heiner
KH
Selzer
Robert H
RH
D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000188:drug therapy*; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects / Q000627:therapeutic use*; D010349:Patient Compliance; D017698:Postmenopause; D017211:Treatment Failure
D004958:Estradiol; D017258:Medroxyprogesterone Acetate