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

Abstract

Purpose: After menopause, women gain abdominal fat and become less sensitive to insulin. We sought to determine whether hormone replacement therapy (HRT) reduced intra-abdominal 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. Copyright © 2005 by The Endocrine Society.