Relationship between hormone replacement therapy use with body fat distribution and insulin sensitivity in obese postmenopausal women.

The aim of this study was to compare the effect of hormone replacement therapy (HRT) on insulin resistance and central adiposity in obese postmenopausal women. Forty-five obese postmenopausal women (16 HRT users and 29 nonusers), with a mean age of 56.6 5.3 years and duration of current, continuous HRT use of 4.7 2.9 years, were included in the study. Subjects were studied using oral glucose tolerance tests, euglycemic clamping, dual photon x-ray absorptiometry, computed tomography, doubly labeled water, and treadmill testing. Insulin sensitivity, total fat, visceral fat, subcutaneous abdominal fat, thigh muscle attenuation, daily physical activity energy expenditure, peak oxygen consumption (VO2) were measured. HRT users had lower body weight (88.0 11.0 v 98.2 15.0 kg, P .05), lower body mass index (33.1 3.5 v 36.8 5.2kg/m 2 , P .05), lower fat mass (38.3 7.3 v 44.1 10 kg, P .05), less visceral adipose tissue (157 47 v 211 81 cm 2 ; P .05), and higher peak VO2 (21.1 4.6 v 17.6 2.2 mL/kg/min, P .001) than nonusers. After adjustment for total fat, we noted a trend for decreased visceral adipose tissue in HRT users (P .09). After adjustment for peak VO2, the decreased visceral adipose tissue persisted in HRT users (P < .01). Insulin sensitivity per killogram of lean body mass did not differ between HRT users (0.51 0.22 mmol/kg/min) and nonusers (0.49 0.22 mmol/kg/min). It was concluded that obese postmenopausal women using HRT have a more favorable body composition and fat distribution pattern than nonusers. Although visceral adipose tissue is decreased in HRT users, insulin sensitivity does not differ between HRT users and nonusers. Copyright © 2001 by W.B. Saunders Company A CLUSTER OF metabolic abnormalities, including dyslipidemia, hypertension, increased central body fat, and glucose intolerance, is commonly referred to as the insulin resistance syndrome, leading to increased risk for cardiovascular disease.1 It is known that central body fat and fasting insulin increase during the menopause transition, which could potentially lead to increased cardiovascular risk. 2,3 Hormone replacement therapy (HRT) given to postmenopausal women might improve these metabolic parameters, thus reducing the risk of cardiovascular disease. 4 Prospective trials of combined estrogen/progestin treatment using anthropometric methods or dual-energy x-ray absorptiometry (DXA) to measure central body fat found that HRT attenuated the increase in truncal body fat compared to placebo over a 1- to 3-year time span.5-8 Although DXA allows for estimation of central fat by its measure of trunk fat, it does not distinguish between intra-abdominal and subcutaneous abdominal fat. Thus, the effects of HRT use on intra-abdominal fat and associated metabolic complications are unknown, particularly in obese women. Studies of HRT and insulin sensitivity have been more controversial, with some studies finding improvement with HRT9,10 and others finding no improvement or even reduced insulin sensitivity. 11-13 Discrepant results among investigators are partially attributable to indirect measurement of insulin sensitivity and small sample sizes. To our knowledge, no study has examined the relationship between current use of HRT, insulin sensitivity, and body composition using direct assessments of these parameters in obese postmenopausal women, a group at considerable risk for adverse metabolic and cardiovascular events. Furthermore, we considered other lifestyle variables such as prestudy weight fluctuation, aerobic fitness, and daily physical activity energy expenditure as possible confounders on body fat distribution and insulin sensitivity with HRT use in the present study. We hypothesized that current HRT use would be associated with lower total and visceral fat and improved insulin sensitivity.