MECHANISMS OF VISCERAL FAT ACCUMULATION IN OLDER WOMEN

这些研究将探索激素替代疗法(HRT)减轻老年女性内脏脂肪积累的机制。由于内脏脂肪是心血管疾病的危险因素，内脏脂肪减少的机制可能解释了HRT的一些心脏保护益处。HRT调节内脏脂肪的假设机制是：1)减轻应激诱导的下丘脑-垂体-肾上腺(HPA)轴活动；2)增加性激素结合球蛋白(SHBG)，导致游离睾酮下降。绝经后妇女将随机接受单独的HRT、单独的安慰剂、HRT加减肥或安慰剂加减肥。应激诱导的HPA轴活动、性激素水平和内脏脂肪的计算机断层扫描将在基线和6个月时进行测量。其具体目的是确定1)HPA轴过度活动是否与内脏肥胖有关，2)HRT是否减弱体重稳定女性中HPA轴的应激诱导活动，3)HRT导致的HPA轴活动的减弱增加减肥期间的内脏脂肪损失，4)内脏脂肪丢失减弱HPA轴的活动不依赖于HRT，以及5)HRT诱导的SHBG增加和游离睾酮的减少与内脏脂肪的变化直接相关。

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.