CHRONIC ANOVULATORY HYPERANDROGENISM: SORTING GENOTYPES

慢性无排卵性高雄激素血症是一种常见的异质性 以多毛症为特征的不明原因的疾病， 少经/闭经，无排卵，不孕，粉刺，高雄激素血症， 黄体生成素/卵泡刺激素比值升高，胰岛素抵抗。因为胰岛素 耐药性通常伴随着已知的冠心病危险因素。 动脉疾病，有推测为慢性无排卵 高雄激素血症提示有更大的冠状动脉倾向 疾病。最近，有人建议早熟的阴毛 是慢性无排卵性高雄激素血症的先兆。如果这个 被证明是真的，他可能会识别和干预 慢性无排卵风险患者亚组中的早期患者 高雄激素血症及其相关并发症。初步数据 支持类固醇合成酶的基因分析，特别是21- 羟基酶(CyP21)。这项建议的假设是：1)预- 成熟的阴毛先于慢性无排卵性高雄激素血症 部分患者；2)性腺和/或肾上腺类固醇激素异常 生产将FSH的分泌限制在门槛以下 排卵所需的浓度和3)有有用的遗传因素 和/或与高血压风险增加相关的激素标志物 慢性无排卵性高雄激素血症。日本血吸虫的基因分型 候选基因结合序列评估 早产/过度男性化的患者，连续 促性腺激素排泄量的测定及重复评价 胰岛素敏感性指数将被用来检验这些假说。 临床特征与激素和激素检测结果的相关性 基因评估可能有助于解开导致事件的序列 慢性无排卵性高雄激素血症。

Chronic anovulatory hyperandrogenism is a common heterogeneous disorder of unknown etiology characterized by hirsutism, oligo/amenorrhea, anovulation, infertility, acne, hyperandrogenism, increased LH/FSH ratio, and insulin resistance. Because insulin resistance is often accompanied by known risk factors for coronary artery disease, it has been speculated that chronic anovulatory hyperandrogenism indicates a greater propensity for coronary artery disease. Recently, it has been suggested that premature pubic hair is a harbinger of chronic anovulatory hyperandrogenism. If this proves to be true, it may he possible to identify and intervene earlier in the subset of patients at risk for chronic anovulatory hyperandrogenism and its associated complications. Preliminary data supports genotype analysis of steroidogenic enzymes especially 21- hydroxylase (CYP21). The hypotheses of this proposal are: 1) pre- mature pubic hair precedes chronic anovulatory hyperandrogenism in some patients; 2) the abnormal gonadal and/or adrenal steroid production limits FSH secretion to below the threshold concentrations needed for ovulation and 3) there are useful genetic and/or hormonal markers associated with an increased risk for chronic anovulatory hyperandrogenism. Genotype analysis of candidate genes in conjunction with sequential evaluation of patients with premature/excessive virilization, serial determinations of gonadotropin excretion and repeated assessments of insulin sensitivity will be used to test these hypotheses. Correlation of clinical features with results of hormonal and genetic evaluations may help unravel the sequence of events leading to chronic anovulatory hyperandrogenism.