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、心血管疾病发病率、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DHEA/DHEA-S代谢的生理调节剂;高胰岛素血症降低正常受试者和多囊卵巢综合征（PCOS）女性的血清DHEA-S，同时相反地增加雄烯二酮（D4-A）和睾酮水平。 循环DHEA-S和睾酮/雄烯二酮的不同相关性结合DHEA饮食效应的动物数据表明，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）的女性有不规则的月经周期和雄激素过多。 此外，患有PCOS的女性已被证明是胰岛素抵抗的，与其频繁的肥胖无关。 患有PCOS的女性也经常有LH平均水平升高，LH脉冲频率和幅度增加。 脉冲幅度和脉冲频率的增加可能继发于垂体反应性增加和/或刺激垂体的GnRH量增加，而脉冲频率的增加可能仅继发于下丘脑GnRH频率增加，表明下丘脑作用部位，也可能是垂体作用部位。 胰岛素和LH都被证明可以增加卵巢雄激素的体外产生，并且任何一种的升高都可能导致体内卵巢雄激素的过量产生。 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，高胰岛素血症可能导致LH水平升高，因为体外证据表明垂体具有胰岛素受体，胰岛素可直接调节垂体LH释放。 因此，本研究旨在研究高胰岛素血症在女性LH水平升高中的作用。 将在研究结束时进行数据分析。 迄今为止，40名预期受试者中已有11名入组。

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.