ANDROGEN BLOCKADE AND SENSITIVITY OF THE GNRH PULSE GENERATOR

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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. Increased androgen levels appear to mediate this decrease in sensitivity, as sensitivity can be restored with the androgen receptor blocker flutamide. Adolescent hyperandrogenemia is thought to be a precursor of PCOS, and a subset of adolescent girls with hyperandrogenemia have decreased hypothalamic sensitivity to progesterone similar to their adult counterparts with PCOS. We hypothesize that flutamide will restore hypothalamic progesterone sensitivity in these girls by blocking the effects of androgens. LH (GnRH) pulse frequency will be assessed before and after 7 days of oral estradiol and progesterone in hyperandrogenic adolescent girls who have been pretreated for 28 days with flutamide. The slope of the percentage change in LH pulse frequency as a function of Day 7 progesterone level will be used as a measure of hypothalamic progesterone sensitivity. Hypothalamic progesterone sensitivity in the girls pretreated with flutamide will be compared to hypothamic progesterone sensitivity in historic controls who did not receive flutamide.