Menopause: The Journal of The North American Menopause Society Vol. 22, No. 3, pp. 279/288 DOI: 10.1097/gme.0000000000000305 * 2014 by The North American Menopause Society

Dietary isoflavones and bone mineral density during midlife and the menopausal transition: cross-sectional and longitudinal results from the Study of Women’s Health Across the Nation Phytoestrogen Study Gail A. Greendale, MD,1 Chi-hong Tseng, PhD,1 Weijuan Han, MS,1 Mei-Hua Huang, DrPH,1 Katherine Leung, MS,2 Sybil Crawford, PhD,2 Ellen B. Gold, PhD,3 L. Elaine Waetjen, MD,4 and Arun S. Karlamangla, PhD, MD1 Abstract Objective: This study aims to examine cross-sectional and longitudinal relations between dietary intake of isoflavones and bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) in black, white, Chinese, and Japanese women during the menopausal transition. Methods: We tested whether tertiles of isoflavone intake were associated with baseline BMD when all women were premenopausal or early perimenopausal. To analyze whether isoflavone intake was associated with longitudinal BMD, we fitted piecewise linear models to repeated measurements of baseline-normalized LS or FN BMD as functions of time before or after the final menstrual period (FMP) date. Results: Multiply adjusted mean FN BMD values of premenopausal Japanese women were monotonically positively related to isoflavone consumption (P for trend = 0.0003). Otherwise, no statistically significant baseline associations were observed. During the period of 1 year before the FMP through 5 years after the FMP, all participants lost LS and FN BMD. Loss was unrelated to isoflavone intake, except for Japanese women during the period of 1 year before the FMP to 2 years after the FMP: higher tertiles of isoflavone intake were associated with greater annual LS BMD loss rates (P for trend = 0.01) and FN loss rates (P for trend = 0.04). Conclusions: In Japanese women, higher isoflavone intake is associated with higher peak FN BMD but also with greater rates of LS and FN BMD loss during the menopausal transition. Results for the other racial/ethnic groups did not support a relation between dietary intake of isoflavones and either peak BMD or BMD loss during the menopausal transition. Key Words: Isoflavones Y Bone density Y Menopausal transition Y Cohort study.

Received March 7, 2014; revised and accepted June 9, 2014. From the 1Division of Geriatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA; 2Department of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, MA; 3 Department of Epidemiology and Preventive Medicine, University of California at Davis, Davis, CA; and 4Department of Obstetrics and Gynecology, UC Davis Medical Center, Davis, CA. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Aging, National Institute of Nursing Research, Office of Research on Women’s Health, or National Institutes of Health. Funding/support: The Study of Women’s Health Across the Nation received grant support from the National Institutes of Health, Department of Health and Human Services, through the National Institute on Aging, the National Institute of Nursing Research, and the National Institutes of Health Office of Research on Women’s Health (grants U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, and U01AG012495). The Study of Women’s Health Across the Nation Phytoestrogen Study was supported by grant AG030448. W.H. was also supported, in part, by grant 1P30 AG028748. Financial disclosure/conflicts of interest: None reported. Address correspondence to: Gail A. Greendale, MD, Division of Geriatrics, David Geffen School of Medicine at UCLA, 10945 Le Conte Ave, Suite 2339, Los Angeles, CA 90095-1687. E-mail: [email protected]

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hytoestrogensVheterocyclic phenols found in plant foodsVconsist mainly of isoflavones, lignans, and coumestans. These compounds, especially the isoflavone class, gained prominence because of their associations with lower rates of hormone-dependent malignancies and have since been associated with prevention of other chronic diseases, including osteoporosis.1 and estrogen receptor-A and are predominantly agonists based on transcriptional activation assays.6,7 However, predicting the effects of isoflavones on estrogen pathways is challenging because of the following reasons: compounds vary in their affinity for estrogen receptor-> and estrogen receptor-A; conformational effects on estrogen receptors differ; agonist or antagonist properties may depend on circulating estradiol levels or phytoestrogen concentrations; Menopause, Vol. 22, No. 3, 2015

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and isoflavones modify the metabolism and bioavailability of endogenous sex steroids in ways that may either increase or decrease endogenous hormone levels or bioavailability.3,4,6

Dietary isoflavones and bone mineral density during midlife and the menopausal transition: cross-sectional and longitudinal results from the Study of Women's Health Across the Nation Phytoestrogen Study.

This study aims to examine cross-sectional and longitudinal relations between dietary intake of isoflavones and bone mineral density (BMD) at the lumb...
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