Physiologic and social stressors and health during menopausal transition

绝经过渡期间的生理和社会压力源与健康

• 批准号: 10669217
• 负责人: Emily Oken
• 金额: $ 37.53万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10669217
• 关键词: Acceleration; Address; Adipose tissue; Adult; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Anxiety; Attention; Behavior; Behavioral; Blood Pressure; Body Composition; Cardiometabolic Disease; Cardiovascular Diseases; Cerebrovascular Disorders; Cholesterol; Data; Dementia; Development; Disease; Electronics; Environmental Risk Factor; Exposure to; Fasting; Future; Genetic; Gestational Diabetes; Glucose; Goals; Guidelines; Health; Hour; Hypertension; Impaired cognition; Insulin; Investigation; Life; Lipids; Longitudinal Studies; Longterm Follow-up; Measures; Mediating; Memory; Menopause; Menstruation; Mental Depression; Metabolic; Methods; Neurobehavioral Manifestations; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Obesity; Outcome; Outcome Assessment; Perimenopause; Perinatal; Postmenopause; Pregnancy; Premenopause; Process; Quality of life; Questionnaires; Research Priority; Resources; Risk; Risk Factors; Roentgen Rays; Series; Sleep; Sleep disturbances; Statistical Data Interpretation; Stress; Testing; Time; Vasomotor; Violence; Visceral; Weight; Weight Gain; Woman; Work; Wrist; actigraphy; adverse childhood events; blood pressure elevation; body system; cardiometabolic risk; cardiometabolism; cardiovascular disorder risk; clinical care; cognitive function; cohort; dementia risk; depressive symptoms; diaries; disorder risk; early pregnancy; experience; follow-up; gestational weight gain; interest; men; middle age; neuropsychiatric symptom; neuropsychiatry; neuroregulation; physiologic stressor; poor health outcome; poor sleep; postpartum weight; pregnancy disorder; prospective; racism; recruit; reproductive; reproductive senescence; screening; sex; social; social stressor; study population; synergism; vascular cognitive impairment and dementia; vasomotor symptoms; waist circumference

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.

在围绝经期间，妇女经历了巨大的变化，超越了月经的停止，包括 加速衰老过程的变化，从而提高了心脏代谢疾病的风险，血管 认知障碍和痴呆（VCID）和阿尔茨海默氏病（AD）病理学的贡献。代谢 在围绝经期可能出现或更糟的危险因素包括中央肥胖，血液的增加 压力，葡萄糖和非HDL胆固醇与后来的2型糖尿病有关 梅利氏菌，心血管疾病和痴呆症。许多绝经妇女也经历神经精神病学 变化包括血管舒适不稳定性的症状，睡眠障碍，抑郁，动画和记忆 问题，代表了生活质量的主要损害，可能是重要的性别特定风险因素 VCID和AD引起的心脏代谢疾病和痴呆症。许多研究表征了 心脏代谢性疾病和成年中痴呆的遗传和行为危险因素。较少的 注意力集中在生理压力和社会压力上，这些压力源影响所有身体系统并增强多重 风险因素，作为这些疾病的贡献者。绝对风险因性别和生命而有所不同：何时绝经 与男性相比，女性患CVD和痴呆症的风险低，随后和之后的风险急剧增加 更年期过渡。生殖过渡期间的终身社会压力源和生理压力源独特 对于女性，可以实质上说明心脏代谢性疾病和痴呆症的性别特定风险。然而， 很少有研究与前瞻性纵向随访有关这些关系的深入研究。这个项目将 检验我们的总体假设，即终生对社会压力较高的围绝经师妇女 以及重要的复制过渡期间的身体压力源 - 怀孕，外围时期和 围绝经期 - 会有更大的心脏代谢风险，更多的神经精神病和认知符号，以及 睡眠持续时间和质量较差。非常普遍的有趣暴露包括身体压力源（过量 妊娠体重增加，血糖/妊娠糖尿病，血压升高/高血压 怀孕的疾病和产后减肥过多）以及社会压力（不良儿童期 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 关系由不良重量轨迹介导。为了解决这些假设，我们将利用项目 Viva是1999 - 2002年怀孕早期招募的持续，高度参与的妇女（平均年龄32岁） 几年），每年紧随其后近20年。该提案提供了一个特殊的机会来通知 通过利用出色的现有数据和资源，包括20多年 在5年内的高质量预期评估。此外，与提议的集成 Brigham/Harvard的压力和神经调节中心的生殖衰老健康结果将扩大 PV通过与项目1和所有核心的合作工作的影响。