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.
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