Physiologic and social stressors and health during menopausal transition

在围绝经期，妇女经历的戏剧性变化超出了月经停止，包括 加速衰老过程的改变，从而增加心脏代谢疾病、血管疾病、 在认知障碍和痴呆（VCID）以及阿尔茨海默病（AD）病理学中的作用。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、血液流变学异常、 血压、葡萄糖和非HDL胆固醇，这些与2型糖尿病的后期发展有关 糖尿病、心血管疾病和痴呆。许多围绝经期妇女也经历神经精神病 变化包括血管不稳定、睡眠障碍、抑郁、焦虑和记忆的症状 问题，这是对生活质量的主要损害，可能是重要的性别特异性风险因素， VCID和AD引起的心血管代谢疾病和痴呆。许多研究表明， 心脏代谢疾病和中年痴呆的遗传和行为危险因素。少 注意力集中在生理和社会压力上，这些压力影响到所有身体系统， 风险因素，作为这些疾病的贡献者。绝对风险因性别和生命阶段而异： 女性患心血管疾病和痴呆症的风险低于男性，在治疗期间和治疗后， 更年期生育过渡期的终生社会压力源和生理压力源 对妇女的影响可能在很大程度上解释了心脏代谢疾病和痴呆症的性别特异性风险。然而， 很少有研究通过前瞻性纵向随访深入探讨这些关系。该项目将 测试我们的总体假设，即围绝经期妇女一生中接触社会压力更大 在重要的生育过渡期--怀孕、围产期， 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， 睡眠时间和质量较差。感兴趣的高度普遍的暴露包括生理应激源（过度 妊娠期体重增加、妊娠期糖尿病、血压升高/高血压 妊娠期疾病和产后体重过多）以及社会压力因素（不良童年 事件、种族主义和暴力风险以及金融不稳定）。此外，我们假设这些 关系由不利的重量轨迹来调节。为了解决这些假设，我们将利用项目 Viva，一个持续的、高度参与的队列，招募了1999-2002年怀孕早期的妇女（平均年龄32岁 年），并每年随访近20年。这一提议提供了一个难得的机会， 通过利用现有的优秀数据和资源，包括20多年来为老年妇女提供的临床护理 高质量的前瞻性评估。此外，与拟议的 布里格姆/哈佛生殖衰老健康结果的压力和神经调节中心将扩大 通过与项目1和所有核心的协作，实现PV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.