Estrogen in the prevention of atherosclerosis - A randomized, double-blind, placebo-controlled trial

Background: Although observational studies suggest that estrogen replacemen t therapy (ERT) reduces cardiovascular morbidity and mortality in postmenop ausal 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 preexis ting cardiovascular disease. Design: Randomized, double-blind, placebo-controlled trial. Setting: University-based clinic. Patients: 222 postmenopausal women 45 years of age or older without preexis ting cardiovascular disease and with low-density lipoprotein cholesterol le vels of 3.37 mmol/L or greater (greater than or equal to 130 mg/dL). Intervention: unopposed micronized 17 beta -estradiol (1 mg/d) or placebo. All women received dietary counseling. Women received lipid-lowering medica tion if their low-density lipoprotein cholesterol level exceeded 4.15 mmol/ L (160 mg/dL). Measurements: The rate of change in intima-media thickness of the right dis tal common carotid artery far wall in computer image processed B-mode ultra sonograms obtained at baseline and every 6 months during the 2-year trial. Results: In a multivariable mixed-effects model, among women who had at lea st one follow-up measurement of carotid intima-media thickness (n = 199), t he 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 progres sion rates was 0.0053 mm/y (95% Cl, 0.0001 to 0.0105 mm/y) (P = 0.046). Amo ng women who did not receive lipid-lowering medication (n = 77), the placeb o-estradiol difference between average rates of progression was 0.0147 mm/y (Cl, 0.0055 to 0.0240) (P = 0.002). Average rates of progression did not d iffer between estradiol and placebo recipients who took lipid-lowering medi cation (n = 122) (P > 0.2). Conclusions: overall, the average rate of progression of subclinical athero sclerosis was slower in healthy postmenopausal women taking unopposed ERT w ith 17 beta -estradiol than in women taking placebo. Reduction In the progr ession of subclinical atherosclerosis was seen in women who did not take li pid-lowering medication but not in those who took these medications.