The primary hypothesis to be tested is that 17B-estradiol (estrogen) will reduce the progression of early atherosclerosis if initiated soon after menopause when the vascular endothelium (lining of blood vessels) is relatively healthy versus later when the endothelium has lost its responsiveness to estrogen. Ultrasonography will be used to measure the rate of change in the thickness of the carotid artery.

A total of 504 postmenopausal women will be randomized according to their number of years since menopause, less than 6 years or 10 years or more, to receive either oral 17B-estradiol 1 mg daily or a placebo. Women with a uterus will also use vaginal progesterone gel 4% (or a placebo gel) the last ten days of each month. The vaginal progesterone will be distributed in a double-blind fashion along with the randomized treatment so that only women exposed to active treatment will receive active progesterone. Participants will receive ultrasonography at baseline and every 6 months throughout the 2 to 5 years (average 3 years) of randomized treatment.

Accepts Healthy Volunteers

Inclusion Criteria:

• Women with a serum estradiol level 25 pg/ml or less
• No period for 6 months or more
• Postmenopausal less than 6 years, OR 10 years or longer

Exclusion Criteria:

• Clinical signs, symptoms, or personal history of cardiovascular disease
• Women who have had a hysterectomy only and no oophorectomy (since time from menopause cannot be determined)
• Diabetes mellitus or fasting serum glucose 140 mg/dL or greater
• Uncontrolled hypertension (diastolic blood pressure 110 mmHg or greater)
• Thyroid disease (untreated)
• Serum creatinine greater than 2.0 mg/dL
• Plasma triglyceride levels greater than 500 mg/dL
• Life threatening disease with prognosis less than 5 years
• Cirrhosis or liver disease
• History of deep vein thrombosis or pulmonary embolism
• History of breast cancer
• Current hormone replacement therapy (HRT)