EFFECT OF ORAL DHEA ON INSULIN SENSITIVITY & LH IN NORMAL WOMEN

肾上腺激素脱氢表雄酮（DHEA）及其硫酸盐（DHEA- s）与胰岛素水平、心血管发病率、癌症、肥胖和糖尿病呈负相关。然而，这种关联的机制尚不清楚。胰岛素作为脱氢表雄酮/脱氢表雄酮- s代谢的生理调节剂；高胰岛素血症降低了正常受试者和多囊卵巢综合征（PCOS）女性的血清DHEA-S，而相反地增加了雄烯二酮（D4-A）和睾酮水平。循环DHEA- s和睾酮/肾上腺二酮的不同相关性结合DHEA饮食影响的动物数据表明，DHEA- s和睾酮可能因此对胰岛素分泌和作用产生相反的影响。患有多囊卵巢综合征（PCOS）的女性有月经周期不规律和多源性。此外，患有多囊卵巢综合征的女性被证明具有胰岛素抵抗性，这与她们经常肥胖无关。患有多囊卵巢综合征的女性通常也有LH平均水平升高，LH脉冲频率和幅度增加。脉冲振幅的增加可能是继发于垂体反应性的增加和/或刺激垂体的GnRH量的增加，而脉冲频率的增加只能是继发于下丘脑GnRH频率的增加，这表明下丘脑的作用部位可能也有垂体的作用部位。胰岛素和黄体生成素在体外均可增加卵巢雄激素的产生，两者的升高都可能导致体内卵巢雄激素产生过剩。胰岛素也降低性激素结合球蛋白水平（SHBG），从而增加游离雄激素浓度。最后，有可能高胰岛素血症导致黄体生成素水平升高，因为有体外证据表明垂体有胰岛素受体，胰岛素可能直接调节垂体黄体生成素释放。因此，本研究旨在探讨高胰岛素血症在女性LH水平升高中的作用。数据分析将在研究结束时进行。到目前为止，预计的40名受试者中有11名已经注册。

The adrenal hormones dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) have been negatively correlated with insulin levels, cardiovascular morbidity, cancer, obesity and diabetes. However, the mechanism of the association is unclear. Insulin acts as a physiological regulator of DHEA/DHEA-S metabolism; hyperinsulinemia decreases serum DHEA-S in normal subjects and in women with polycystic ovary syndrome (PCOS), while increasing androstenedione (D4-A) and testosterone levels conversely. The divergent correlations of circulating DHEA-S and testosterone/adrostenedione combined with the animal data of diet effects of DHEA suggest that DHEA-S and testosterone may therefore exert opposing effects on insulin secretion and action. Women with the Polycystic Ovary Syndrome (PCOS) have irregular menstrual cycles and hyperandogenism. In addition, women with PCOS have been shown to be insulin resistant, independent of their frequent obesity. Women with PCOS also often have elevated mean levels of LH, with an increased LH pulse frequency and amplitude. The increases in both pulse amplitude, which could be secondary to an increased pituitary responsiveness and/or an increased amount of GnRH stimulating the pituitary, and in pulse frequency, which could only be secondary to an increase in hypothalamic GnRH frequency, suggests a hypothalamic site of action and possibly also a pituitary site of action as well. Insulin and LH have both been shown to increase ovarian androgen production in vitro and elevations of either may contribute to excess ovarian androgen production in vivo. Insulin also lowers sex hormone binding globulin levels (SHBG) thereby increasing free androgen concentrations. Finally, it is possible that hyperinsulinemia contributes to the elevated LH levels as there is in vitro evidence that the pituitary has insulin receptors and that insulin may directly modulate pituitary LH release. Thus, this study is designed to examine the role of hyperinsulinemia in elevated LH levels in women. Data analysis will be performed at study end. To date, 11 of the 40 anticipated subjects have been enrolled.