The primary goal of this randomized, controlled trial is to determine if ERT stabilizes, retards, and/or reverses the progression of atherosclerosis in postmenopausal women. We will further evaluate the association of lipid and non-lipid factors of ERT-mediated reduction in the progression of early atherosclerosis. Ultrasonography will be used to measure the rate of change in the thickness of the carotid artery. Blood samples will be used for measuring lipid and non-lipid mediators of ERT.

A total of 222 healthy postmenopausal women 46 to 80 years old without CVD symptoms will be randomized to receive either micronized 17B-estradiol (Estrace) 1mg/day, or a matching placebo tablet daily. All women will be on a low fat/low cholesterol diet, and will receive pravastatin if their LDL cholesterol level exceeds 160 mg/dL. Participants will undergo ultrasonography at baseline and every 6 months throughout the 2 years of randomized treatment. Measurements of lipid and non-lipid biochemical markers will also be done at baseline and every 6 months.

Accepts Healthy Volunteers

Inclusion Criteria:

• Postmenopausal female (serum estradiol less than 20 pg/ml)
• 46 to 80 years old
• Fasting LDL-C levels 130 to 210 mg/dL
• Triglyceride levels less than 400 mg/dL
• Current non-smoker

Exclusion Criteria:

• Clinical evidence of cardiovascular disease
• HDL-C level less than 30 mg/dL
• Fasting blood glucose greater than 200 mg/dL
• Previous hormonal replacement therapy (non-contraceptive) over 10 years duration and/or current use within 1 month
• Uncontrolled hypertension
• Untreated thyroid disease
• Renal insufficiency
• Clinical evidence of congestive heart failure
• Life threatening disease with prognosis less than 5 years
• Alcohol intake greater than 5 drinks per day (1 drink = 1 1/2 oz distilled spirits, 4 oz wine, or 12 oz beer) or substance abuse (intravenous drug abuse, cocaine use)
• History of estrogen dependent cancer or detected at screening or any other disorder precluding use of ERT
• Hot flashes greater than 5 per day which interfere with daily activity and preclude randomization to placebo.