Mounting evidence suggests that exposure to exogenous estrogens and estrogenic compounds such as selective estrogen receptor modulators (SERMs) and tibolone may increase the risk of stroke in women. Since phytoestrogens, plant-derived estrogens, are known to possess estrogenic effects similar to SERMs and have been marketed as natural and """"""""safe"""""""" alternatives to estrogen therapy, significant concerns have been raised as to whether high exposure to phytoestrogens may confer the same risk of stroke. Another intriguing question has also arisen whether endogenous estrogen levels play a role in predicting stroke risk. We propose to address these questions in a prospective cohort of 74,942 adult Chinese women enrolled in the Shanghai Women's Health Study (SWHS) from 1997 to 2000. Specifically, we propose to verify incident stroke cases identified in this cohort during follow-up through medical record review. We will examine the association between dietary intake of soy phytoestrogens and risk of total stroke and stroke subtypes in the full cohort. Repeated dietary measurements will be used for the analyses. In addition, we propose to conduct a nested case-control study among postmenopausal women to investigate the association of ischemic stroke (the predominant type of stroke) with urinary levels of isoflavonoids, a biomarker of systemic exposure to phytoestrogens, and with blood levels of estradiol, estrone, testosterone, and sex hormone- binding globulin. We will include 1500 incident cases of ischemic stroke and 1500 individually matched controls. Isoflavonoids and sex hormones will be measured in biological samples collected at baseline using LC-MS based methods. The SWHS represents an exceptional opportunity to address the targeted questions given its large size, prospective design, high follow-up rates, extensive exposure and disease outcome information collected over the past decade, availability of biological samples, and the unique study population with a high level of soy consumption and low prevalence of hormone therapy use. Results of this proposed study will fill important gaps in our knowledge regarding the role of phytoestrogen and endogenous estrogen exposure in the etiology of stroke in women.

Public Health Relevance

This proposed study is intended to fill important gaps in our knowledge about whether high exposure to plant estrogens (phytoestrogens) and endogenous estrogens in women may raise the risk of stroke, one of the leading causes of death and long-term disability in the United States and many other countries. Study results may contribute to the development of new strategies for the primary prevention of stroke.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Cardiovascular and Sleep Epidemiology (CASE)
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Ludlam, Shari
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Vanderbilt University Medical Center
Internal Medicine/Medicine
Schools of Medicine
United States
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Yu, Danxia; Zhang, Xianglan; Shu, Xiao-Ou et al. (2016) Dietary glycemic index, glycemic load, and refined carbohydrates are associated with risk of stroke: a prospective cohort study in urban Chinese women. Am J Clin Nutr 104:1345-1351
Wu, Qi-Jun; Xiang, Yong-Bing; Yang, Gong et al. (2015) Vitamin E intake and the lung cancer risk among female nonsmokers: a report from the Shanghai Women's Health Study. Int J Cancer 136:610-7
Yu, Danxia; Shu, Xiao-Ou; Li, Honglan et al. (2015) Dietary isoflavones, urinary isoflavonoids, and risk of ischemic stroke in women. Am J Clin Nutr 102:680-6
Wu, Sheng Hui; Shu, Xiao Ou; Milne, Ginger et al. (2015) Uric acid correlates to oxidation and inflammation in opposite directions in women. Biomarkers 20:225-31
Yu, Danxia; Zhang, Xianglan; Xiang, Yong-Bing et al. (2014) Adherence to dietary guidelines and mortality: a report from prospective cohort studies of 134,000 Chinese adults in urban Shanghai. Am J Clin Nutr 100:693-700
Wu, Sheng Hui; Shu, Xiao Ou; Chow, Wong-Ho et al. (2014) Nonexercise physical activity and inflammatory and oxidative stress markers in women. J Womens Health (Larchmt) 23:159-67
Yu, Danxia; Zhang, Xianglan; Xiang, Yong-Bing et al. (2014) Association of soy food intake with risk and biomarkers of coronary heart disease in Chinese men. Int J Cardiol 172:e285-7
Yang, W S; Shu, X O; Gao, J et al. (2013) Prospective evaluation of type 2 diabetes mellitus on the risk of primary liver cancer in Chinese men and women. Ann Oncol 24:1679-85
Wu, Q J; Xie, L; Zheng, W et al. (2013) Cruciferous vegetables consumption and the risk of female lung cancer: a prospective study and a meta-analysis. Ann Oncol 24:1918-24
Takata, Yumie; Zhang, Xianglan; Li, Honglan et al. (2013) Fish intake and risks of total and cause-specific mortality in 2 population-based cohort studies of 134,296 men and women. Am J Epidemiol 178:46-57

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