METFORMIN AND SENSITIVITY OF GNRH PULSE GENERATOR SUPPRESSION IN HYPERANDROGEMIA

二甲双胍与雄激素过多症中 GNRH 脉冲发生器抑制的敏感性

• 批准号: 8167194
• 负责人: John C Marshall
• 金额: $ 4.01万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167194
• 关键词: Adolescent; Adult; Computer Retrieval of Information on Scientific Projects Database; Estradiol; Fasting; Female Adolescents; Frequencies; Funding; Grant; Hour; Hyperinsulinism; Hypothalamic structure; Institution; Insulin; Measures; Mediating; Metformin; Oral; Physiologic pulse; Progesterone; Research; Research Personnel; Resources; Source; United States National Institutes of Health; Woman; girls; improved; insulin sensitivity

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 患有 PCOS 的女性 GnRH 脉冲发生器对雌二醇和黄体酮抑制的敏感性降低。 青少年高雄激素血症被认为是成人多囊卵巢综合症的先兆。 在之前的研究中，虽然一些高雄激素女孩的下丘脑对孕酮的敏感性降低，与患有多囊卵巢综合症的成年女孩相似，但其他女孩则保持正常的下丘脑孕酮敏感性。 下丘脑黄体酮敏感性降低的女孩尽管体重指数相似，但空腹胰岛素水平较高，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青春期女孩的下丘脑黄体酮敏感性。 将在高雄激素青春期女孩接受二甲双胍 1000 mg BID 治疗 3 个月之前和之后 7 天口服雌二醇和黄体酮之前和之后评估 LH (GnRH) 脉冲频率。 黄体酮调整后的 11 小时 LH 脉冲频率变化将用作下丘脑黄体酮敏感性的测量。