A lifecourse approach to women's cardiometabolic and bone health: from fertility to perimenopause

项目总结/摘要 此应用程序响应PA-17-091：生育状态作为整体健康的标志 在她们的生育年龄，许多妇女经历了大量的体重增加，骨密度下降， 肌肉质量和心脏代谢健康恶化，每一个都预测了以后的发病率和死亡率。最 女性在这个生命阶段有一次或多次怀孕，并且很大一部分女性（高达1/3），包括 许多曾成功受孕并怀孕的妇女都经历过生育力低下或不育。 不孕症，定义为在12个月的无保护性交后无法怀孕，因此是世界上最常见的不孕症之一。 最常见于育龄期成年人。越来越多的证据表明生育率- 相关的特征预测未来的健康风险，包括体重过度增加，骨质疏松症，心血管疾病， 疾病（CVD）和2型糖尿病。 我们提出的项目的总体目标是检验我们的假设，即有证据表明生育能力受损的妇女 在围绝经期会有更多不良的身体成分、骨骼健康和心脏代谢结果。我们 提出一个前瞻性纵向队列研究设计作为解决拟议目标的最佳方法。 我们将利用来自Project Viva的数据，这是一个高度参与的现有队列，其中包括1000多名社会人口统计学 我们已经从不同的女性那里收集了关于体重、饮食和其他健康状况的详细信息， 从1999-2002年入组时开始，并从那时起不断更新。 通过经验证的自我报告、临床或研究措施对暴露进行评估，并将包括几项 生育率的最新指标：受孕周期;妊娠和产次;不孕症的诊断和治疗; 多囊卵巢综合征（PCOS）的诊断以及睾酮的测量，一个定义 PCOS的特征;抗苗勒管激素（AMH）水平，卵巢储备的客观标志物。 结果包括身体成分（脂肪、瘦肉和骨量）、心血管健康和 代谢健康，并将在亲自研究访问中使用金标准措施进行评估。以来 在研究开始时，我们还严格收集了有关广泛行为，健康措施， 环境因素、社会和家庭经历。 从拟议的一系列调查结果将告知临床护理的妇女从生殖 关于筛查和长期随访的指南，以及未来的研究 优先事项本提案提供了一个利用现有未处理数据的绝佳机会， 资源，包括在5年项目期内进行20多年的高质量前瞻性评估。

Project Summary/Abstract This application is responsive to PA-17-091: Fertility Status as a Marker for Overall Health Across their reproductive years, many women experience substantial weight gain, declines in bone density and muscle mass, and worsening cardiometabolic health, each predicting later life morbidity and mortality. Most women have one or more pregnancies during this lifestage, and a large subset of women (up to 1/3), including many who have successfully conceived and carried a previous pregnancy, experience subfertility or infertility. Infertility, defined as the inability to conceive after 12 months of unprotected intercourse, is thus one of the most common conditions among reproductive age adults. A growing body of evidence suggests that fertility- related characteristics predict future health risks including excess weight gain, osteoporosis, cardiovascular disease (CVD), and type 2 diabetes mellitus. The overall goal of our proposed project is to test our hypothesis that women with evidence of impaired fertility will have more adverse body composition, bone health, and cardiometabolic outcomes in perimenopause. We propose a prospective longitudinal cohort study design as the optimal approach to address the proposed aims. We will leverage data from Project Viva, a highly engaged existing cohort of over 1000 socio-demographically diverse women from whom we have already collected detailed information on weight, diet, and other health behaviors beginning at enrollment in 1999-2002, and updated continually since. Exposures are assessed with validated self-reported, clinical, or research measures and will include several time-updated markers of fertility: cycles to conception; gravidity and parity; infertility diagnoses and treatments; diagnosis of polycystic ovary syndrome (PCOS) as well as measurement of testosterone, a defining characteristic of PCOS; and levels of anti-Müllerian hormone (AMH), an objective marker of ovarian reserve. Outcomes include markers of body composition (fat, lean, and bone mass), cardiovascular health, and metabolic health and will be assessed using gold-standard measures at an in-person research visit. Since study inception, we have also rigorously collected data on a wide set of behaviors, health measures, environmental factors, and social and family experiences. Results from the proposed series of investigations will inform clinical care for women from the reproductive years through perimenopause, guidelines regarding screening and long-term follow-up, and future research priorities. This proposal provides an exceptional opportunity to leverage outstanding existing data and resources and include over 20 years of high quality prospective assessments within a 5-year project period.