HYPERGONADOTROPIC HYPOGONADISM--PHYSIOLOGY AND TREATMENT

有相当一部分不孕症患者 促性腺激素水平与他们的性腺功能减退症，并已事先 原发性性腺衰竭伴不可逆转的不孕症 然而，在这一群体中， 患者，病理生理学未知。 骨盆新技术 超声波检查、受体和生物测定以及分子生物学现在允许 促性腺激素作用缺陷谱的鉴定， 而不是性腺衰竭。 盆腔超声检查 在超过一半的女性中发现了残留的卵泡， 高促性腺激素性腺功能减退症 LH β基因突变- 亚基基因已在具有异常受体结合的人中被鉴定。 在其他患者中，LH和FSH受体结合抑制剂均已被应用于 鉴定 一旦这些缺陷被记录下来，这些患者就有了 潜在的性腺反应，如果性腺刺激可以 更正。 该项目旨在使用盆腔超声检查， 促性腺激素受体测定筛选高促性腺激素患者 卵泡生成或促性腺激素受体异常的证据 以确定这种异常的频率。 患者 然后将进一步研究异常受体结合以纯化 促性腺激素调节剂或结合抑制剂，并鉴定特异性 基因缺陷，以便最终开发出特定的治疗方法。 患有高促性腺激素性性腺功能减退症的男性和女性都将入组， 一段时间的观察，以表征已知的盈亏过程 性腺衰竭，随后进行适当的性别治疗 类固醇替代，以抑制其内源性促性腺激素。 期间 试验、系列检查和受体测定将在 努力更仔细地描述病理生理学特征， 临床和生化参数，将预测治疗 响应能力。

A significant population of patients with infertility has elevated gonadotropin levels associated with their hypogonadism, and has previously been though to have primary gonadal failure with irreversible infertility. However, pregnancies have intermittently been reported in this group of patients, with unknown pathophysiology. New techniques of pelvic ultrasonography, receptor and bioassays, and molecular biology now allow the identification of a spectrum of defects of gonadotropin action, rather than gonadal failure, in these patients. Pelvic ultrasonography has identified residual ovarian follicles in over half the women with hypergonadotropic hypogonadism in our series. A mutation of the LH beta- subunit gene has been identified in a man with abnormal receptor binding. In other patients, both LH and FSH receptor binding inhibitors have been identified. Once such defects are documented, these patients have the potential for gonadal responsiveness if the gonadal stimulus can be corrected. This project seeks to use pelvic ultrasonography and gonadotropin receptor assays to screen hypergonadotropic patients for evidence of ovarian folliculogenesis or abnormal gonadotropin receptor binding to establish the frequency of such abnormalities. Patients with abnormal receptor binding will then be studied further to purify the gonadotropin modulators or binding inhibitors and to identify the specific gene defects, so that specific treatments can ultimately be developed. Both men and women with hypergonadotropic hypogonadism will be enrolled for a period of observation, to characterize the known waxing and waning course of gonadal failure, followed by subsequent treatment with appropriate sex steroid replacement, to suppress their endogenous gonadotropins. during the trial, serial examinations and receptor assays will be performed in an effort to more carefully characterize the pathophysiology and to identify clinical and biochemical parameters that will be predictive of therapeutic responsiveness.