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

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 在卵泡期，LH脉冲频率通常在睡眠期间降低。这些减少可能对支持FSH合成和分泌很重要。多囊卵巢综合征（PCOS）与持续快速的促性腺激素释放激素（GnRH）脉冲频率有关，这种异常可能导致PCOS的许多激素表现。虽然一项先前的研究表明，PCOS患者的夜间LH频率略有下降，但方法学问题限制了解释。此外，我们的初步数据表明，未经治疗的PCOS患者的夜间LH频率并没有降低，而PCOS患者的夜间LH频率降低在雄激素受体阻断剂的作用下得到恢复。我们假设，与正常（卵泡晚期）对照组相比，PCOS患者的睡眠相关LH脉冲频率降低不太明显，但PCOS患者的睡眠相关LH频率降低与4周后的（卵泡晚期）对照相似。将对PCOS受试者和正常对照受试者进行研究。将确定基线LH脉冲频率（15：00 - 07：00），并将正式评估睡眠。然后在重新评估LH脉冲频率之前给予氟替卡松4周。将通过分层混合效应模型分析LH脉冲频率。我们将使用方差分析最小二乘均值的线性对比来检验我们的先验研究假设：（a）PCOS和对照组在Fluorescent前LH频率的平均清醒与睡眠差异是否相同，以及（B）Fluorescent后两组LH频率的平均清醒与睡眠差异是否相同。

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.