We will conduct a randomized, placebo-controlled, double-blind, coronary angiographic/carotid ultrasonographic clinical trial of hormonal replacement therapy (HRT) in postmenopausal women. There will be three treatment arms: 1) Micronized 17beta-estradiol 1 mg per day (days 1-30); 2) Micronized 17beta-estradiol plus medroxyprogesterone acetate 5 mg per day (for 12 consecutive days); and 3) Usual care/placebo. All arms will receive lipid-lowering therapy, low-fat low cholesterol diet and pravastatin in sufficient dosage to reduce LDL-cholesterol levels below 130 mg/dL. This trial will evaluate both lipid and non-lipid effects of HRT on the coronary and carotid arterial wall under conditions which eliminate self-selection and differential interaction with the medical care system. Our study will draw from the large ethnically diverse population of greater Los Angeles. Two hundred and sixteen subjects will be randomized into a three year treatment trial with repeat coronary angiograms after three years. Coronary angiograms will be computer image processed to minimize measurement error for the primary trial outcome measure. There will be two secondary arterial outcome measures: 1) Global change score (GSC) derived from human panel read coronary angiograms; and 2) Ultrasound measures of common carotid arterial wall intima-media thickness (IMT). Clinical measures will include lipids, lipoproteins, apolipoproteins, estradiol and medroxyprogesterone levels, urinary prostanoid metabolites, and insulin/glucose metabolism. This angiographic/ultrasound clinical trial will allow us to study the direct arterial wall effects of two commonly prescribed hormonal replacement regimens, estrogen replacement therapy and cyclical progestin opposed estrogen replacement therapy. Hard data on this critical issue is needed for physicians to weigh the risk/benefit concerning HRT in postmenopausal women in order to set practice patterns.
