MECHANISMS OF VISCERAL FAT ACCUMULATION IN OLDER WOMEN

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These studies will explore mechanisms by which hormone replacement therapy (HRT) attenuates visceral fat accumulation in older women. Since visceral fat is a risk factor for cardiovascular disease, mechanisms of visceral fat attenuation may explain some of the cardioprotective benefits of HRT. The hypothesized mechanisms of visceral fat modulation by HRT are via 1) an attenuating effect on stress-induced hypothalamic- pituitary-adrenal (HPA) axis activity, and 2) an increase in sex- hormone binding globulin (SHBG) resulting in decreased free testosterone. Postmenopausal women will be randomized to HRT alone, placebo alone, HRT plus weight loss, or placebo plus weight loss. Measurement of stress-induced HPA axis activity, sex hormone levels, and visceral fat by computed tomography will be conducted at baseline and at 6 months. The specific aims are to determine whether 1) HPA axis hyperactivity is associated with visceral obesity, 2) HRT attenuates stress-induced activity of the HPA axis in weight-stable women, 3) HRT-induced attenuation of HPA axis activity augments visceral fat loss during a period of weight reduction, 4) visceral fat loss attenuates HPA axis activity independent of HRT, and 5) HRT-induced increases in SHBG and decreases in free testosterone are directly related to changes in visceral adiposity.