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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在卵泡期，黄体生成素的脉冲频率在睡眠期间通常会降低。这些减少可能对支持FSH的合成和分泌很重要。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，这种异常可能是PCOS的许多激素表现的原因。尽管先前的一项研究表明，多囊卵巢综合征患者夜间促黄体生成激素的频率略有下降，但方法学问题限制了解释。此外，我们的初步数据表明，未经治疗的多囊卵巢综合征患者夜间黄体生成素频率并未减少，而雄激素受体阻断可恢复多囊卵巢综合征患者夜间黄体生成素频率的下降。我们假设，与正常(卵泡晚期)对照组相比，在氟他胺治疗前，PCOS患者睡眠相关的黄体生成素频率降低不那么明显，但在氟他胺治疗4周后，PCOS患者睡眠相关的黄体生成素频率降低与(卵泡晚期)对照组相似。研究对象为多囊卵巢综合征患者和正常对照组。将确定基线促黄体生成素脉冲频率(从1500到0700小时)，并将正式评估睡眠。在重新评估促黄体生成素脉冲频率之前，将给予氟他胺4周。采用分层混合效应模型对LH光脉冲频率进行分析。我们将使用ANOVA最小二乘均值的线性对比度来检验我们的先验研究假设：(A)在服用氟他胺之前，PCOS和对照组的平均觉醒与睡眠频率差异是否相同，以及(B)在氟他胺治疗后，两组患者的平均觉醒与睡眠频率差异是否相同。

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.