MECHANISMS OF VISCERAL FAT ACCUMULATION IN OLDER WOMEN

这些研究将探索激素替代疗法（HRT）减轻老年妇女内脏脂肪堆积的机制。由于内脏脂肪是心血管疾病的危险因素，内脏脂肪衰减的机制可以解释HRT的一些心脏保护作用。HRT调节内脏脂肪的假设机制是：1)对应激诱导的下丘脑-垂体-肾上腺（HPA）轴活性的减弱作用；2)性激素结合球蛋白（SHBG）的增加导致游离睾酮的降低。绝经后妇女将被随机分为单独HRT组、单独安慰剂组、HRT加减肥组或安慰剂加减肥组。在基线和6个月时，通过计算机断层扫描测量应力诱导的HPA轴活性、性激素水平和内脏脂肪。具体目的是确定1)HPA轴过度活跃是否与内脏肥胖相关，2)HRT减弱体重稳定女性应激诱导的HPA轴活性，3)HRT诱导的HPA轴活性减弱在减肥期间增加内脏脂肪减少，4)内脏脂肪减少减弱HPA轴活性独立于HRT， 5) HRT诱导的SHBG升高和游离睾酮降低与内脏肥胖的变化直接相关。

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.