This supplement to the Study of Women's Health Across the Nation (SWAN) II is designed to provide funds for the on time fielding of the seventh follow-up clinic visit for the SWAN cohort. SWAN is a multicenter, multiethnic, community based, longitudinal study to characterize the biological and psychosocial changes that occur during the menopausal transition and to assess their effect on women's health. Current and past funding (SWAN I and II) support six years of follow-up, at the end of which 60% of observable transitions to postmenopause will have occurred. This application requests funding for 10 months, for the timely initiation of the seventh follow-up clinical visit. A separate SWAN Iii application requests funds to finish the seventh follow-up and complete a total of 10 follow-up visits, so that the study can capture 91% of observable transitions to postmenopause and thus provide a more representative sample. The additional data will permit a focus on the late perimenopausal and early postmenopausal periods that have not been well studied in the literature. As women reach the end of early postmenopause (two years following the final menstrual period), we will shift from an annual to a bi-annual clinic visit with mail and telephone contact in the alternating years. This will set the stage for cost-effective and less intensive follow-up beyond SWAN Iii. We will continue our current observations as well as undertake new science in each of the four scientific project areas (ovarian aging; symptoms, risk factors, functioning, and aging; cardiovascular risk factors; and determinants and outcomes of bone mass). The new science includes measurement of: vascular stiffness to assess early cardiovascular disease, salivary cortisol levels, vertebral morphometry using newly developed DEXA technology, and circulating androgens and total bioactive estrogens using an assay system developed by SWAN investigators. In addition, we will focus on linking the midlife experience to age-related outcomes and chronic diseases, including physical and cognitive function. The additional follow-up will also contribute to and expand the SWAN biological specimen repository (annual blood and urine samples as well as DNA and immortalized cells), a separately funded component that broadens the opportunities to address future hypotheses about health, disease, and aging. With SWAN Iii, many of the original goals of SWAN will be brought to fruition. We will build upon the rich foundation developed during SWAN I and II, and ultimately, link these data to subsequent age-related health outcomes. ? ? INTEGRATIVE SCIENCE AND THE NEXUS TO AGING (OVERVIEW AND INTEGRATIVE). ? ? DESCRIPTION (provided by applicant): SWAN is exceptional in the breadth of data that are being collected across scientific areas. In the scientific projects that are encompassed in the subsequent 100 pages of this application, specific study hypotheses relating to each of the primary scientific areas are presented. However, by approaching scientific areas individually, we are in danger of over-simplifying the biological and social processes involved. A great strength of SWAN is our ability to approach the study of women at mid-life from a multi-disciplinary perspective. An Integrative Committee has been formed and charged with fostering the development of multidisciplinary lines of investigation. The Integrative Committee will also link the data collected in SWAN to the larger body of knowledge related to aging. At the outset of SWAN III, the mean age of the cohort will be almost 53 years of age and 884 women will have transitioned to postmenopause. This maturation of the study population invites explicit consideration of the nexus between the menopausal transition and chronological aging. The Integrative Committee will focus on the interface between menopause and aging, taking advantage of the unique cohort and breadth of data being collected. ? ? While a number of integrative lines of investigation will be pursued, in the following brief section, we preview one integrative approach to aging and menopause from conceptualization through data collection and analysis. As will be described in this preview, to gain a more comprehensive perspective of the biology and implications of the menopausal transition, ultimately we must move beyond the simplistic concept of estrogen deficiency. This will require a shift to a new paradigm. As an illustration of how this can be accomplished in SWAN, the following section develops an exploratory approach that represents a new way to pull together information across scientific disciplines. ? ?
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