Estrogen in the prevention of atherosclerosis. A randomized, double-blind, placebo-controlled trial.
BACKGROUND
Although observational studies suggest that estrogen replacement therapy (ERT) reduces cardiovascular morbidity and mortality in postmenopausal women, use of unopposed ERT for prevention of coronary heart disease in healthy postmenopausal women remains untested.


OBJECTIVE
To determine the effects of unopposed ERT on the progression of subclinical atherosclerosis in healthy postmenopausal women without preexisting cardiovascular disease.


METHODS
Randomized, double-blind, placebo-controlled trial.


METHODS
University-based clinic.


METHODS
222 postmenopausal women 45 years of age or older without preexisting cardiovascular disease and with low-density lipoprotein cholesterol levels of 3.37 mmol/L or greater (>/=130 mg/dL).


METHODS
Unopposed micronized 17beta-estradiol (1 mg/d) or placebo. All women received dietary counseling. Women received lipid-lowering medication if their low-density lipoprotein cholesterol level exceeded 4.15 mmol/L (160 mg/dL).


METHODS
The rate of change in intima-media thickness of the right distal common carotid artery far wall in computer image processed B-mode ultrasonograms obtained at baseline and every 6 months during the 2-year trial.


RESULTS
In a multivariable mixed-effects model, among women who had at least one follow-up measurement of carotid intima-media thickness (n = 199), the average rate of progression of subclinical atherosclerosis was lower in those taking unopposed estradiol than in those taking placebo (-0.0017 mm/y vs. 0.0036 mm/y); the placebo-estradiol difference between average progression rates was 0.0053 mm/y (95% CI, 0.0001 to 0.0105 mm/y) (P = 0.046). Among women who did not receive lipid-lowering medication (n = 77), the placebo-estradiol difference between average rates of progression was 0.0147 mm/y (CI, 0.0055 to 0.0240) (P = 0.002). Average rates of progression did not differ between estradiol and placebo recipients who took lipid-lowering medication (n = 122) (P > 0.2).


CONCLUSIONS
Overall, the average rate of progression of subclinical atherosclerosis was slower in healthy postmenopausal women taking unopposed ERT with 17beta-estradiol than in women taking placebo. Reduction in the progression of subclinical atherosclerosis was seen in women who did not take lipid-lowering medication but not in those who took these medications.
Hodis
H N
HN
Atherosclerosis Research Unit, University of Southern California, 2250 Alcazar Street, CSC 132, Los Angeles, CA 90033, USA. watcher@usc.edu
Mack
W J
WJ
Lobo
R A
RA
Shoupe
D
D
Sevanian
A
A
Mahrer
P R
PR
Selzer
R H
RH
Liu Cr
C R
CR
Liu Ch
C H
CH
Azen
S P
SP
D000368:Aged; D000369:Aged, 80 and over; D001161:Arteriosclerosis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D002339:Carotid Arteries / Q000473:pathology; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018450:Disease Progression; D004311:Double-Blind Method; D004958:Estradiol / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D006801:Humans; D008875:Middle Aged; D010349:Patient Compliance; D017698:Postmenopause; D014280:Triglycerides / Q000097:blood; D017539:Tunica Intima / Q000473:pathology
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D004958:Estradiol