Examining the hormonal dynamics that characterize the menopausal transition by accurately assaying reproductive ligands is central to understanding the impact of menopause on women's health from midlife through old age. Fundamentally, the Endocrinology of the Menopause/CLASS Laboratory component will examine the dynamics and provide the endocrinologic scaffolding for all other projects in SWAN. We will characterize the hormonal changes associated with the menopausal transition and precisely relate these to their clinical manifestations, explore new areas of endocrine importance, and extend the study of hormonal characteristics from the early to late postmenopause. We will challenge the traditional concept of the menopausal transition as simply a loss of ovarian estradiol secretion to a more integrated and data driven model of a shift from an estrogen dominant to an androgen dominant balance of sex steroids modulated by a dynamic hepatic globulin system. Through SWAN I, II and III we have shown, both cross-sectionally and longitudinally: 1) sex hormone binding globulin (SHBG) to be most strongly associated with cardiovascular risk factors, metabolic syndrome, body composition, insulin, and glucose levels;2) androgens to be strongly associated with cardiovascular risk factors, metabolic syndrome, body composition, insulin and glucose levels, and sexual function;3) follicle stimulating hormone to be strongly associated with bone loss, vasomotor symptoms and timing of the final menstrual period;4) a transient increase in adrenal androgen secretion coincides with the late perimenopausal drop in estradiol secretion;5) only modest associations of estradiol with vasomotorsymptoms, metabolic and hemostatic factors but not bone loss. These findings provide endocrinological support for the evolution in thinking of the menopausal transition as an integrated shift from an estrogen dominant to an androgen dominant state with health risks associated with the magnitude of that shift. To characterize completely the natural history of the menopausal transition, we will pursue the following Specific Aims: 1) Add measures of circulating A and E1 to the annually measured T and E2 to provide a more complete estimate of total circulating estrogens and androgens. We shall calculate the equilibrium among these four steroids and the relationship of the equilibrium to SHBG, both cross-sectionally and longitudinally;2) Measure the isoforms of SHBG and relate the relative proportions to sex steroid levels and ethnic differences, both cross-sectionally and longitudinally;and 3) Determine the degree to which the measured circulating adrenal androgens are associated with health outcomes in women traversing the menopause. We will continue serum sampling of previously measured hormones.

Public Health Relevance

These studies will increase our understanding of the hormonal physiology of the entire menopausal transition and assist in the development of evidence-based paradigms for treating peri- and postmenopausal health concerns.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AG012495-18
Application #
8069169
Study Section
Special Emphasis Panel (ZAG1-ZIJ-8 (J3))
Program Officer
Sherman, Sherry
Project Start
1994-09-30
Project End
2014-04-30
Budget Start
2011-08-01
Budget End
2012-04-30
Support Year
18
Fiscal Year
2011
Total Cost
$1
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Hanley, Carrie; Matthews, Karen A; Brooks, Maria M et al. (2018) Cardiovascular fat in women at midlife: effects of race, overall adiposity, and central adiposity. The SWAN Cardiovascular Fat Study. Menopause 25:38-45
Chung, Hsin-Fang; Pandeya, Nirmala; Dobson, Annette J et al. (2018) The role of sleep difficulties in the vasomotor menopausal symptoms and depressed mood relationships: an international pooled analysis of eight studies in the InterLACE consortium. Psychol Med 48:2550-2561
Dugan, Sheila A; Gabriel, Kelley Pettee; Lange-Maia, Brittney S et al. (2018) Physical Activity and Physical Function: Moving and Aging. Obstet Gynecol Clin North Am 45:723-736
B├ęcares, Laia; Zhang, Nan (2018) Perceived Interpersonal Discrimination and Older Women's Mental Health: Accumulation Across Domains, Attributions, and Time. Am J Epidemiol 187:924-932
Everson-Rose, Susan A; Clark, Cari J; Wang, Qi et al. (2018) Depressive symptoms and adipokines in women: Study of women's health across the nation. Psychoneuroendocrinology 97:20-27
Hedgeman, Elizabeth; Hasson, Rebecca E; Karvonen-Gutierrez, Carrie A et al. (2018) Perceived stress across the midlife: longitudinal changes among a diverse sample of women, the Study of Women's health Across the Nation (SWAN). Womens Midlife Health 4:
Waetjen, L Elaine; Crawford, Sybil L; Chang, Po-Yin et al. (2018) Factors associated with developing vaginal dryness symptoms in women transitioning through menopause: a longitudinal study. Menopause 25:1094-1104
Ruppert, K; Cauley, J; Lian, Y et al. (2018) The effect of insulin on bone mineral density among women with type 2 diabetes: a SWAN Pharmacoepidemiology study. Osteoporos Int 29:347-354
Crawford, Sybil L; Crandall, Carolyn J; Derby, Carol A et al. (2018) Menopausal hormone therapy trends before versus after 2002: impact of the Women's Health Initiative Study Results. Menopause :
Karlamangla, Arun S; Burnett-Bowie, Sherri-Ann M; Crandall, Carolyn J (2018) Bone Health During the Menopause Transition and Beyond. Obstet Gynecol Clin North Am 45:695-708

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