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. Polycystic ovary syndrome (PCOS) is a leading cause of infertility. A slow GnRH pulse frequency appears to be requisite for follicle stimulating hormone (FSH) secretion and egg development. However, most women with PCOS have persistently rapid GnRH pulse frequency. This results in elevated luteinizing hormone (LH) levels, increased LH:FSH ratios, and irregular ovulation. We plan to treat women with PCOS with 4 weeks of exogenous estradiol and progesterone in mid-luteal levels in order to suppress GnRH pulse frequency. In addition, half of the women will be randomized to take the androgen receptor blocker flutamide for 4 weeks before and during the study in order to block the effects of PCOS-associated hyperandrogenemia. We hypothesize that this treatment will result in increased secretion of FSH and normalization of the intraovarian hormonal milieu which, in turn, should lead to improved chances of ovulation following discontinuation of the study medications. The primary outcome is ovulation which will be documented by hormone testing and vaginal ultrasound. Subjects who ovulate will have the option of continuing with cyclic estradiol and progesterone treatment to see if ovulation continues.
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