METFORMIN AND SENSITIVITY OF GNRH PULSE GENERATOR SUPPRESSION IN HYPERANDROGEMIA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 患有多囊卵巢综合征的妇女GnRH脉冲发生器对雌二醇和孕酮抑制的敏感性降低。青春期高雄激素血症被认为是成人多囊卵巢综合征的先兆。在以前的研究中，虽然一些高雄激素女孩与患有多囊卵巢综合征的成年女孩一样，降低了下丘脑孕酮的敏感性，但另一些女孩保持了正常的下丘脑孕酮敏感性。下丘脑孕酮敏感性降低的女孩的空腹胰岛素水平较高，尽管BMI相似，这表明高胰岛素血症可能在一定程度上介导了敏感性的降低。我们假设二甲双胍将通过改善胰岛素敏感性和降低胰岛素水平来改善高雄激素性青春期女孩的下丘脑孕酮敏感性。对高雄激素性青春期女孩口服雌二醇孕酮7天前和服药后3个月分别测定促黄体生成素(GnRH)的脉搏频率。黄体酮调节后11小时内黄体生成素脉冲频率的变化将作为衡量下丘脑孕酮敏感性的指标。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Women with PCOS have decreased GnRH pulse generator sensitivity to suppression by estradiol and progesterone. Adolescent hyperandrogenemia is thought to be a precursor of adult PCOS. In previous studies, while some hyperandrogenic girls have decreased hypothalamic sensitivity to progesterone similar to their adult counterparts with PCOS, others maintain normal hypothalamic progesterone sensitivity. The girls with decreased hypothalamic progesterone sensitivity have higher fasting insulin levels despite similar BMIs, suggesting that hyperinsulinemia may in part mediate the reduction in sensitivity. We hypothesize that metformin will improve hypothalamic progesterone sensitivity in hyperandrogenic adolescent girls by improving insulin sensitivity and lowering insulin levels. LH (GnRH) pulse frequency will be assessed before and after 7 days of oral estradiol and progesterone in hyperandrogenic adolescent girls both before and after 3 months treatment with Metformin 1000 mg BID. Progesterone adjusted change in 11-hour LH pulse frequency will be used as the measure of hypothalamic progesterone sensitivity.