Mechanisms of Sleep-Disordered Breathing in the Menopausal Transition

描述(申请人提供)：虽然最近的流行病学证据表明，阻塞性睡眠呼吸暂停在绝经后妇女中的患病率显著增加，但现有的研究尚未阐明其潜在的机制。该项目的目标是阐明围绝经期妇女激素水平下降、上呼吸道结构和功能的变化以及睡眠障碍呼吸的发展之间的关系。为此，我们建议对正在经历更年期过渡的女性进行一项纵向研究，以检查睡眠呼吸紊乱、上呼吸道软组织结构和上呼吸道塌陷程度的变化。与回溯性或横断性研究不同，这种前瞻性研究设计将允许我们记录受试者随着时间的推移由于激素变化而发生的变化，同时控制包括体重增加、年龄和时间在内的混杂因素。这项拟议研究的目的是：1)确定生殖激素水平(雌二醇、孕酮和睾酮)与睡眠障碍呼吸的变化之间的关系；2)评估更年期过渡期间上呼吸道解剖和脂肪分布的变化，并研究它们与激素水平和睡眠障碍呼吸的关系；以及3)确定更年期过渡期间呼吸道塌陷性的变化。为了实现这些目标，我们将从宾夕法尼亚卵巢老龄化研究(PDA)中招募受试者，这是一项正在进行的前瞻性研究，研究对象是来自费城的300多名非裔美国人和高加索女性，他们之前收集了近10年的荷尔蒙和其他数据，用于通过家庭多导睡眠图和其他程序每年收集的新数据。我们相信，这项研究可能会确定生殖水平如何导致上呼吸道结构和功能的特定变化，从而加速阻塞性睡眠呼吸暂停的发展。这些发现将使我们能够识别绝经后睡眠呼吸障碍的风险女性，并将重点放在这一领域的定制治疗上。

DESCRIPTION (provided by applicant): Although recent epidemiologic evidence has demonstrated that obstructive sleep apnea increases significantly in prevalence among women after the menopausal transition, existing research has not yet elucidated the underlying mechanisms. The goal of this project is to elucidate the relationships between declining hormone levels in perimenopausal women, changes in upper airway structure and function, and the development of sleep-disordered breathing. To do so, we propose to perform a longitudinal study of women going through the menopausal transition that will examine changes in the severity of sleep- disordered breathing, upper airway soft tissue structures and upper airway collapsibility. Unlike retrospective or cross-sectional studies, this prospective study design will allow us to chronicle changes within subjects over time due to hormonal changes, while controlling for confounding factors including weight gain, age and time. The aims of the proposed study are: 1) To determine the relationship between reproductive hormone levels (estradiol, progesterone and testosterone) and change in sleep-disordered breathing; 2) To assess changes in upper airway anatomy and fat distribution over the menopausal transition and examine their relationship to hormone levels and sleep-disordered breathing; and 3) To determine changes in airway collapsibility over the menopausal transition. To accomplish these aims, we will recruit subjects from the Penn Ovarian Aging Study (PDAS), an ongoing prospective study of the menopausal transition in over 300 African-American and Caucasian women from Philadelphia with nearly 10 years of previously collected hormonal and other data, for new data collected yearly by home polysomnography and other procedures. We believe this study is likely to identify how reproductive levels' lead to specific changes in upper airway structure and function, precipitating the development of obstructive sleep apnea. These findings will allow us to identify women at risk for sleep-disordered breathing after menopause and to focus on tailoring treatments in this area.