The effect of hormone replacement therapy on body composition, body fat distribution, and insulin sensitivity in menopausal women: a randomized, double-blind, placebo-controlled trial.

PURPOSE After menopause, women gain abdominal fat and become less sensitive to insulin. We sought to determine whether hormone replacement therapy (HRT) reduced intraabdominal and sc abdominal fat and improved insulin sensitivity in early menopausal women. METHODS Seventy-six postmenopausal women, age 51.6 +/- 3.9 yr with body mass index of 24.9 +/- 3.2 kg/m2, were randomized to conjugated estrogens (0.625 mg) plus medroxyprogesterone acetate (2.5 mg) or placebo daily. Women received a computed tomography scan at the L4-L5 vertebral disk space, a dual x-ray absorptiometry scan, and a euglycemic hyperinsulinemic clamp at baseline, 6 months, 1 yr, and 2 yr. RESULTS Fifty-one women completed the trial and were analyzed (n = 26 on HRT and n = 25 on placebo). Intraabdominal fat, sc abdominal fat, total fat, percent fat, fat-free mass, and weight did not differ between treatment groups by time. Insulin sensitivity did not change in the placebo group, but decreased by 17% in the HRT group by 6 months and persisted at 2 yr (P < 0.01 for treatment by time effect). One year after the trial, insulin sensitivity increased by 25% in women who had taken HRT (P = 0.006 for treatment by time effect), to a level similar to those women in the placebo group. CONCLUSIONS Conjugated estrogens plus medroxyprogesterone acetate reduce insulin sensitivity in menopausal women without affecting body composition or body fat distribution. The reduction in insulin sensitivity is reversible after discontinuing HRT.