Mechanisms of Sleep-Disordered Breathing in the Menopausal Transition

描述（由申请人提供）：尽管最近的流行病学证据表明，阻塞性睡眠呼吸暂停在绝经过渡期后的女性中的患病率显著增加，但现有研究尚未阐明其潜在机制。本项目的目的是阐明围绝经期妇女激素水平下降、上呼吸道结构和功能变化以及睡眠呼吸障碍发生之间的关系。为此，我们建议对经历绝经过渡期的女性进行纵向研究，以检查睡眠呼吸障碍的严重程度、上气道软组织结构和上气道可吸收性的变化。与回顾性或横断面研究不同，这种前瞻性研究设计将使我们能够记录受试者因激素变化而随时间发生的变化，同时控制混杂因素，包括体重增加，年龄和时间。本研究的目的是：1）确定生殖激素水平之间的关系（雌二醇、孕酮和睾酮）和睡眠呼吸障碍的变化; 2）评估绝经过渡期上气道解剖结构和脂肪分布的变化，并检查它们与激素水平和睡眠呼吸障碍的关系;和3）确定绝经过渡期气道通透性的变化。为了实现这些目标，我们将从宾夕法尼亚大学卵巢衰老研究（PDAS）中招募受试者，这是一项正在进行的前瞻性研究，研究来自费城的300多名非洲裔美国人和白人妇女的绝经过渡期，其中有近10年的激素和其他数据，每年通过家庭多导睡眠图和其他程序收集新数据。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，从而促进阻塞性睡眠呼吸暂停的发展。这些发现将使我们能够识别更年期后有睡眠呼吸障碍风险的女性，并专注于这一领域的定制治疗。

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.