Physiologic and social stressors and health during menopausal transition

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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.