HYPERANDROGENEMIA & SLEEP-ASSOCIATED SLOWING OF FOLLICULAR LH FREQUENCY IN PCOS

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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. During the follicular phase, LH pulse frequency normally decreases during sleep. These decreases may be important to support FSH synthesis and secretion. Polycystic ovary syndrome (PCOS) is associated with a persistently rapid gonadotropin hormone-releasing hormone (GnRH) pulse frequency, an abnormality that may account for many of the hormonal manifestations of PCOS. Although one prior study suggests that nocturnal LH frequency decreases slightly in PCOS, methodological issues limit interpretation. Moreover, our preliminary data suggest that nocturnal LH frequency does not decrease in untreated PCOS, and that nocturnal decreases of LH frequency are restored with androgen receptor blockade in women with PCOS. We hypothesize that sleep-associated reduction of LH pulse frequency is less pronounced in PCOS compared to normal (late follicular) controls prior to flutamide, but that sleep-associated LH frequency reduction in PCOS is similar to (late follicular) controls after 4 weeks of flutamide. Subjects with PCOS and normal controls will be studied. Baseline LH pulse frequency will be determined (from 1500 to 0700 h), and sleep will be formally evaluated. Flutamide will then be given for 4 weeks prior to reassessment of LH pulse frequency. LH pulse frequency will be analyzed by way of hierarchical mixed effect models. We will use linear-contrasts of the ANOVA least-squared means to test our a priori research hypotheses: (a) whether the mean wake vs. sleep difference in LH frequency is the same for PCOS and controls prior to flutamide, and (b) whether the mean wake vs. sleep difference in LH frequency is the same for the two groups after flutamide.