Physiologic and social stressors and health during menopausal transition

在围绝经期，女性经历了超越月经停止的戏剧性变化，包括 加速衰老过程从而增加心脏代谢性疾病、血管 对认知障碍和痴呆症(VCID)以及阿尔茨海默病(AD)病理的贡献。新陈代谢 围绝经期可能出现或恶化的危险因素包括中心性肥胖、血液 压力、血糖和非高密度脂蛋白胆固醇与2型糖尿病的后期发展相关 糖尿病、心血管疾病和痴呆症。许多围绝经期妇女也会经历神经精神疾病 变化包括血管运动不稳定、睡眠障碍、抑郁、焦虑和记忆 问题，这些问题是对生活质量的主要损害，可能是与性别相关的重要风险因素 由VCID和AD引起的心脏代谢性疾病和痴呆。大量研究表明， 成年中期心脏代谢性疾病和痴呆的遗传和行为危险因素。较少 人们的注意力集中在生理和社会应激源上，这些应激源影响到所有的身体系统，并使多发性 风险因素，作为这些疾病的贡献者。绝对值风险因性别和生活方式不同而不同：绝经前 女性患心血管疾病和痴呆症的风险比男性低，在手术前后风险显著增加。 更年期过渡。终生社会应激源和生殖过渡期间的生理应激源独特 对女性来说，这可能在很大程度上解释了心脏代谢性疾病和痴呆症的性别风险。然而， 很少有研究通过前瞻性的纵向随访来深入探讨这些关系。该项目将 测试我们的总体假设，即围绝经期女性一生中暴露在更高的社会压力之下 和重要生殖过渡期间的生理应激源--怀孕、围产期和 围绝经期-将有更大的心脏代谢风险，更多的神经精神和认知症状，以及 睡眠时间和质量较差。非常普遍的感兴趣暴露包括生理应激源(过量 妊娠期体重增加、血糖异常/妊娠期糖尿病、血压升高/高血压 怀孕障碍和产后体重超标)以及社会应激源(不良童年 事件、暴露于种族主义和暴力、以及金融不稳定)。此外，我们假设这些 关系是通过不利的体重轨迹来调节的。为了解决这些假设，我们将利用项目 Viva，1999-2002年在怀孕早期招募的持续、高度参与的妇女队列(平均年龄32岁 年)，并在近20年的时间里每年紧随其后。这份提案提供了一个难得的机会，让我们 通过利用优秀的现有数据和资源，包括20多年来为老年妇女提供临床护理 在5年内完成高质量的前瞻性评估。此外，与拟议的 布里格姆/哈佛生殖衰老压力和神经调节中心将扩大健康结果 通过与项目1和所有核心的协作来实现光伏的影响。

During perimenopause, women experience dramatic changes that extend beyond cessation of menses, including alterations that accelerate the aging process and thereby elevate risks for cardiometabolic diseases, vascular contributions to cognitive impairment and dementia (VCID), and Alzheimer’s disease (AD) pathology. Metabolic risk factors that may emerge or worsen in the perimenopausal period include increases in central adiposity, blood pressure, glucose, and non-HDL cholesterol, which are associated with later development of type 2 diabetes mellitus, cardiovascular disease, and dementia. Many perimenopausal women also experience neuropsychiatric changes including symptoms of vasomotor instability, sleep disturbance, depression, anxiety, and memory problems, which represent major detriments to quality of life and may be important sex-specific risk factors for cardiometabolic diseases and dementia caused by both VCID and AD. Numerous studies have characterized genetic and behavioral risk factors for cardiometabolic diseases and dementia in middle adulthood. Less attention has focused on physiologic and social stressors, which affect all body systems and heighten multiple risk factors, as contributors to these diseases. Absolute risks differ by sex and lifestage: while premenopausal women are at lower risk for CVD and dementia than men, risks increase dramatically through and after the menopausal transition. Lifetime social stressors and physiologic stressors during reproductive transitions unique to women may substantially account for the sex-specific risks of cardiometabolic diseases and dementia. Yet, few studies have addressed these relationships in depth with prospective longitudinal follow-up. This Project will test our overall hypothesis that perimenopausal women with higher exposure to social stressors throughout life and physiological stressors during important reproductive transitions—pregnancy, the peripartum period, and the perimenopause—will have greater cardiometabolic risk, more neuropsychiatric and cognitive symptoms, and poorer sleep duration and quality. Highly prevalent exposures of interest include physiological stressors (excess gestational weight gain, dysglycemia/gestational diabetes mellitus, elevated blood pressure/hypertensive disorders of pregnancy, and excess postpartum weight retention) as well as social stressors (adverse childhood events, exposures to racism and violence, and financial instability). Furthermore, we hypothesize that these relations are mediated by adverse weight trajectories. To address these hypotheses, we will leverage Project Viva, an ongoing, highly engaged cohort of women recruited in early pregnancy 1999–2002 (at mean age 32 years) and followed annually for almost 2 decades. This proposal provides an exceptional opportunity to inform clinical care for aging women by leveraging outstanding existing data and resources and including over 20 years of high- quality prospective assessments within a 5-year period. Furthermore, integration with the proposed Brigham/Harvard Center for Stress and Neural Regulation of Reproductive Aging Health Outcomes will expand the impact of PV through collaborative work with Project 1 and all Cores.