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

高雄激素血症

• 批准号: 8167192
• 负责人: Christopher Rolland McCartney
• 金额: $ 6.15万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167192
• 关键词: Accounting; Androgen Receptor; Computer Retrieval of Information on Scientific Projects Database; Data; Flutamide; Frequencies; Funding; Gonadotropin Hormone Releasing Hormone; Grant; Hormonal; Institution; Least-Squares Analysis; Modeling; Physiologic pulse; Polycystic Ovary Syndrome; Research; Research Personnel; Resources; Sleep; Source; Testing; United States National Institutes of Health; Woman; proliferative phase Menstrual cycle

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 在卵泡相期间，LH脉冲频率通常在睡眠期间降低。这些减少对于支持FSH的合成和分泌可能很重要。多囊卵巢综合征（PCOS）与持续快速的促性腺激素激素释放激素（GNRH）脉冲频率有关，这种异常可能会解释PCOS的许多激素表现。尽管一项先前的研究表明，夜间LH频率在PCOS中略有下降，但方法论问题限制了解释。此外，我们的初步数据表明，未经处理的PCOS的夜间LH频率不会降低，并且LH频率的夜间降低会随PCOS女性的雄激素受体阻滞而恢复。我们假设与flutamide之前的正常（晚卵泡）对照相比，PCOS中与睡眠相关的LH脉冲频率的降低不太明显，但是PCOS中与睡眠相关的LH频率降低类似于（晚期Follicular）控制后4周后（晚期）控制。将研究具有PCOS和正常对照的受试者。将确定基线LH脉冲频率（从1500到0700 h），并将对睡眠进行正式评估。然后，在重新评估LH脉冲频率之前，将给予氟氨酰胺4周。 LH脉冲频率将通过分层混合效应模型进行分析。我们将使用ANOVA最小二乘均值的线性对比度来测试我们的先验研究假设：（a）PCOS和对照在Flutamide之前的PCOS和对照中的平均唤醒与睡眠差异是否相同，以及（b）在氟替酰胺后，LH的平均唤醒与LH频率是否相同。