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 #
5U01AG012495-17
Application #
7843593
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
2010-05-15
Budget End
2011-04-30
Support Year
17
Fiscal Year
2010
Total Cost
$788,582
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
Colvin, Alicia; Richardson, Gale A; Cyranowski, Jill M et al. (2017) The role of family history of depression and the menopausal transition in the development of major depression in midlife women: Study of women's health across the nation mental health study (SWAN MHS). Depress Anxiety 34:826-835
Avis, Nancy E; Colvin, Alicia; Karlamangla, Arun S et al. (2017) Change in sexual functioning over the menopausal transition: results from the Study of Women's Health Across the Nation. Menopause 24:379-390
Jackson, Elizabeth A; Ruppert, Kristine; Derby, Carol A et al. (2017) Effect of Race and Ethnicity on Antihypertensive Medication Utilization Among Women in the United States: Study of Women's Health Across the Nation (SWAN). J Am Heart Assoc 6:
Gold, Ellen B; Crawford, Sybil L; Shelton, Janie F et al. (2017) Longitudinal analysis of changes in weight and waist circumference in relation to incident vasomotor symptoms: the Study of Women's Health Across the Nation (SWAN). Menopause 24:9-26
Basu, Rupa; May Wu, Xiangmei; Malig, Brian J et al. (2017) Estimating the associations of apparent temperature and inflammatory, hemostatic, and lipid markers in a cohort of midlife women. Environ Res 152:322-327
Santoro, Nanette; Crawford, Sybil L; El Khoudary, Samar R et al. (2017) Menstrual Cycle Hormone Changes in Women Traversing Menopause: Study of Women's Health Across the Nation. J Clin Endocrinol Metab 102:2218-2229
Putman, Melissa S; Yu, Elaine W; Lin, David et al. (2017) Differences in Trabecular Microstructure Between Black and White Women Assessed by Individual Trabecular Segmentation Analysis of HR-pQCT Images. J Bone Miner Res 32:1100-1108
Wu, Xiangmei May; Basu, Rupa; Malig, Brian et al. (2017) Association between gaseous air pollutants and inflammatory, hemostatic and lipid markers in a cohort of midlife women. Environ Int 107:131-139
El Khoudary, Samar R; Shields, Kelly J; Janssen, Imke et al. (2017) Postmenopausal Women With Greater Paracardial Fat Have More Coronary Artery Calcification Than Premenopausal Women: The Study of Women's Health Across the Nation (SWAN) Cardiovascular Fat Ancillary Study. J Am Heart Assoc 6:
Karlamangla, Arun S; Lachman, Margie E; Han, WeiJuan et al. (2017) Evidence for Cognitive Aging in Midlife Women: Study of Women's Health Across the Nation. PLoS One 12:e0169008

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