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

The number of postmenopausal women is expected to rise markedly in coming years. The increased risk of cardiovascular disease associated with menopause may in part reflect changes in body composition and body fat distribution as well as lowered sensitivity to insulin. This randomized, placebo-controlled trial was aimed at showing whether combined estrogen/progestin replacement (hormone therapy [HT]) can lessen the accumulation of central body fat and thereby improve insulin sensitivity. Seventy-six perimenopausal and early postmenopausal women with a mean age of 52 years were randomized to receive either 0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate orally or a placebo. Fifty-one women completed the 2-year trial. The euglycemic hyperinsulinemic clamp technique was used to assess insulin-stimulated glucose disposal. Fat mass, percent fat, and fat-free mass were estimated by dual-photon x-ray absorptiom-etry, and intraabdominal fat and subcutaneous abdominal fat by computed tomography scanning. The treated and control women were similar demographically at baseline. Fasting glucose levels were higher in placebo recipients. No significant group differences in intraabdominal fat, subcutaneous abdominal fat, total fat, fat-free mass, or percent fat were observed during the study. The same was the case for waist circumference and body weight. Insulin sensitivity decreased 17% in women given HT but the group difference was not significant. Insulin sensitivity per fat-free mass also declined during HT. Among 28 women who reported their food consumption during the study, those on HT had a 12% drop in caloric intake; there was no change in the placebo group. Self-reported carbohydrate intake decreased 16% in women given HT but increased by 2% in placebo recipients. There was no substantial group difference in leisure-time physical activity. No HT-related decrease in insulin sensitivity was noted in 17 women who returned 1 year after discontinuing HT or placebo. Combination HT lowers insulin sensitivity without significantly altering body composition or the distribution of body fat in nonobese women early in menopause. The insulin resistance is attributed to decreased peripheral insulin sensitivity rather than altered endogenous glucose production. The effect is reversible by discontinuing HT.