EFFECTS OF HORMONE-THERAPY ON BONE-MINERAL DENSITY - RESULTS FROM THEPOSTMENOPAUSAL ESTROGEN PROGESTIN INTERVENTIONS (PEPI) TRIAL/

Objective.-To assess the effects of hormone therapy on bone mineral de nsity (BMD) in the spine and hip of postmenopausal women. Design.-A 3- year, multicenter, randomized, double-blinded, placebo-controlled clin ical trial. Participants.-A total of 875 healthy women aged 45 to 64 y ears recruited at 7 clinical centers. Interventions.-Treatments were ( 1) placebo; (2) conjugated equine estrogens (CEE), 0.625 mg/d; (3) CEE , 0.625 mg/d plus medroxyprogesterone acetate (MPA), 10 mg/d for 12 d/ mo; (4) CEE, 0.625 mg/d plus MPA, 2.5 mg/d daily; or (5) GEE, 0.625 mg /d plus micronized progesterone (MP), 200 mg/d for 12 d/mo. Main Outco me Measures.-Bone mineral density at baseline, 12 months, and 36 month s. Results.-Participants assigned to the placebo group lost an average of 1.8% of spine BMD and 1.7% of hip BMD by the 36-month visit, while those assigned to active regimens gained BMD at both sites, ranging f rom 3.5% to 5.0% mean total increases in spinal BMD and a mean total i ncrease of 1.7% of BMD in the hip. Changes in BMD for women assigned t o active regimens were significantly greater than those assigned to pl acebo. Women assigned to CEE plus continuous MPA had significantly gre ater increases in spinal BMD (increase of 5%) than those assigned to t he other 3 active regimens (average increase, 3.8%). Findings were sim ilar among those adhering to assigned therapy, although, among adheren t participants, there were no significant differences in BMD changes a mong the 4 active treatment groups, Older women, women with low initia l BMD, and those with no previous hormone use gained significantly mor e bone than younger women, women with higher initial BMD, and those wh o had used hormones previously. Conclusions.-Postmenopausal women assi gned to placebo demonstrated decreased BMD at the spine and hip, where as women assigned to estrogen therapy increased BMD during a 36-month period, These findings demonstrate that estrogen replacement therapy i ncreases BMD at clinically important sites.