DESCRIPTION (provided by applicant): This is the amended competing renewal application of the Study of Women's Health Across the Nation (SWAN), a 7-site longitudinal cohort study initiated in 1994 in response to RFA AG-94-002. SWAN was mandated "to characterize the chronology of the biological and psychosocial antecedents and sequelae of the menopausal transition (MT) and the effect of this transition on subsequent health and risk factors for age- related disease", and to extend this information from White women to "...the range of peri-menopausal experiences in women of other racial/ethnic background(s)." A total of 3302 Black, Chinese, Japanese, Hispanic and White women were enrolled, with 78% completing up to 13 visits spanning the premenopause to early post-menopause (PM). Thus far, SWAN has described the natural history of the MT -- its timing, patterns of hormonal changes, and symptoms and factors related to them - and their relation to disease risk indicators. During SWAN V, we will extend observations through the late PM, a necessary step to assess the impact of the MT on age-related diseases. Our specific aims are to: 1) complete the characterization of the natural history of reproductive aging through the late PM; 2) evaluate the impact of reproductive aging through the late PM on health outcomes clinically relevant to women in their 60s and 70s, including: cognitive and physical function, psychological well-being, sleep, bone and cardiometabolic health, urogenital symptoms, sexual function and vaginal health; and 3) identify potential underlying mechanisms linking reproductive aging and health by assessing the relation of inflammation, hemostasis and adipokines to the occurrence and progression of biological, functional and clinical outcomes and delineating the interrelationships of body size and composition, race/ethnicity and socioeconomic status with these outcomes. The SWAN V Core protocol will be completed at 7 study sites, with bone and cardiovascular studies at 4 sites and actigraphy studies in a subset of women at all sites. Longitudinal specimens from the SWAN Repository will enable characterization of skeletal markers, adrenal hormones, hemostasis, inflammation, and adipokines across the MT into PM. The Coordinating Center will provide the necessary organizational infrastructure, statistical resources, and timely dissemination of high quality SWAN data. The CLIA-certified Central Laboratory will perform or coordinate with other laboratories to provide accurate, high volume assays, adopting new methods as needed to provide state- of-the-art data. SWAN is uniquely positioned to fill important scientific gaps in understanding of the impact of the MT on women's health in their 60s and 70s and to facilitate the application of new knowledge to clinical practice. With 1.5 decades of both calendar time and "menopause time", SWAN V can disaggregate the contributions of aging and the MT to women's health, address difficult and critical questions about the temporal nature of MT-disease associations, assess differences by race/ethnicity, and provide insights into modifiable factors relevant to the design of innovative prevention and treatment programs for aging women.

PUBLIC HEALTH RELEVANCE: SWAN will fill important gaps in understanding the impact of the menopausal transition and mid-life aging on women's health and functioning in the postmenopausal years. Accordingly, it will provide useful information to guide clinical decisions in mid-life and beyond in women who have diverse life experiences and socioeconomic and racial/ethnic characteristics.