METFORMIN AND SENSITIVITY OF GNRH PULSE GENERATOR SUPPRESSION IN HYPERANDROGEMIA

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 PCOS妇女GnRH脉冲发生器对雌二醇和孕酮抑制的敏感性降低。 青少年高雄激素血症被认为是成年PCOS的前兆。 在以前的研究中，虽然一些高雄激素女孩的下丘脑对孕酮的敏感性降低，类似于他们的成年PCOS患者，但其他人保持正常的下丘脑孕酮敏感性。 下丘脑孕酮敏感性降低的女孩尽管BMI相似，但空腹胰岛素水平较高，这表明高胰岛素血症可能部分介导了敏感性的降低。 我们假设二甲双胍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血症青春期女孩的下丘脑孕酮敏感性。 将在口服雌二醇和孕酮7天之前和之后，评估高雄激素性青春期女孩在接受美托洛尔1000 mg BID治疗3个月之前和之后的LH（GnRH）脉冲频率。 11小时LH脉冲频率的预后调整变化将用作下丘脑孕酮敏感性的测量。

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.