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Hormone Replacement Therapy, Insulin Sensitivity, and Abdominal Obesity in Postmenopausal Women

Department of Medicine, Division of Gerontology at the University of Maryland School of Medicine, and the Baltimore Geriatric Research, Education and Clinical Center (GRECC), VA Maryland Health Care System, Baltimore, Maryland

OBJECTIVE—The purpose of this study was to determine whether insulin sensitivity differs between postmenopausal women taking estradiol, women on estrogen plus progesterone hormone replacement therapy (HRT), and women not on HRT and whether differences are explained by the differences in total and/or abdominal adiposity and fat deposition in the muscle.

RESEARCH DESIGN AND METHODS—We studied 28 obese, sedentary postmenopausal Caucasian women. Women taking oral estrogen (n = 6) were matched for age (57 ± 3 vs. 58 ± 2 years), weight (87.9 ± 6.0 vs. 83.0 ± 3.9 kg), and BMI (33.9 ± 1.7 vs. 33.9 ± 1.9 kg/m²) with women not on HRT (n = 6). Eight women taking oral estrogen plus progesterone were matched with eight different women not on HRT for age (59 ± 2 vs. 60 ± 2 years), weight (82.8 ± 3.7 vs. 83.7 ± 4.1 kg), and BMI (30.7 ± 1.0 vs. 29.9 ± 1.3 kg/m²).

RESULTS—VO_2max (maximal aerobic capacity), percentage of fat, total body fat mass, and fat-free mass (FFM) were similar between groups. Visceral fat, subcutaneous abdominal fat, sagittal diameter, and mid-thigh low-density lean tissue (intramuscular fat) did not differ by hormone status. Basal carbohydrate and fat utilization was not different among groups. Fasting plasma glucose and insulin did not differ by hormone use. Glucose utilization (M) was measured during the last 30 min of a 3-h hyperinsulinemic-euglycemic clamp (40 mU · m² · min^-1). Postmenopausal women taking oral estrogen had a 31% lower M than women not on HRT (42.7 ± 4.0 vs. 61.7 ± 4.7 µmol · kg_FFM · min^-1, P < 0.05). M was 26% lower in women taking estrogen plus progesterone (44.0 ± 3.5 vs. 59.7 ± 6.2 µmol · kg_FFM · min^-1, P < 0.05) than women not on HRT. M/I, the amount of glucose metabolized per unit of plasma insulin (I), an index of insulin sensitivity, was 36% lower in women taking estrogen compared with matched women not on HRT (P < 0.05) and 28% lower in women taking estrogen plus progesterone compared with matched women not on HRT (P < 0.05).

CONCLUSIONS—Postmenopausal women taking oral estrogen or those taking a combination of estrogen and HRT are more insulin-resistant than women not on HRT, even when women are of comparable total and abdominal adiposity.

Abbreviations: CT, computed tomography • DXA, dual-energy X-ray absorptiometry • FFM, fat-free mass • HRT, hormone replacement therapy • HU, Hounsfield unit • I, plasma insulin • IGT, impaired glucose tolerance • ITT, insulin tolerance test • IVGTT, intravenous glucose tolerance test • M, glucose utilization • OGTT, oral glucose tolerance test • WHR, waist-to-hip ratio

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