Arterial imaging outcomes and cardiovascular risk factors in recently menopausal women: a randomized trial.

BACKGROUND: Whether menopausal hormone therapy (MHT) protects against cardiovascular disease (CVD) remains unclear.

OBJECTIVE: To assess atherosclerosis progression and CVD risk factors after MHT initiated in early menopause.

DESIGN: Randomized, controlled trial. (ClinicalTrials.gov: NCT00154180).

SETTING: Nine U.S. academic centers.

PARTICIPANTS: Healthy menopausal women aged 42 to 58 years between 6 and 36 months from last menses without prior CVD events who had a coronary artery calcium (CAC) score less than 50 Agatston units and had not received estrogen or lipid-lowering therapy for at least 90 days.

INTERVENTION: Oral conjugated equine estrogens (o-CEE), 0.45 mg/d, or transdermal 17β-estradiol (t-E2), 50 mcg/d, each with 200 mg of oral progesterone for 12 days per month, or placebo for 48 months.

MEASUREMENTS: Primary end point was annual change in carotid artery intima-media thickness (CIMT). Secondary end points included changes in markers of CVD risk.

RESULTS: Of 727 randomly assigned women, 89.3% had at least 1 follow-up CIMT and 79.8% had CIMT at 48 months. Mean CIMT increases of 0.007 mm/y were similar across groups. The percentages of participants in whom CAC score increased did not differ significantly across groups. No changes in blood pressure were observed with o-CEE or t-E2. Low- and high-density lipoprotein cholesterol levels improved and levels of C-reactive protein and sex hormone-binding globulin but not interleukin-6 increased with o-CEE. Insulin resistance decreased with t-E2. Serious adverse events did not differ by treatment.

LIMITATION: Power to compare clinical events was insufficient.

CONCLUSION: Four years of early MHT did not affect progression of atherosclerosis despite improving some markers of CVD risk.

PRIMARY FUNDING SOURCE: Aurora Foundation.