Phytoestrogen and Endogenous Estrogen Exposure and Risk of Stroke

描述(申请人提供)：越来越多的证据表明，接触外源性雌激素和雌激素化合物，如选择性雌激素受体调节剂(SERM)和替勃龙，可能会增加女性中风的风险。由于植物雌激素，即植物来源的雌激素，已知具有与SERM类似的雌激素样作用，并被作为雌激素治疗的天然和安全的替代品而上市，因此，人们对高暴露于植物雌激素是否会导致相同的中风风险提出了重大关注。另一个耐人寻味的问题也出现了，内源性雌激素水平是否在预测中风风险中发挥作用。我们建议在1997年至2000年上海妇女健康研究(SWHS)中登记的74942名成年中国女性的前瞻性队列中解决这些问题。具体地说，我们建议在随访期间通过医疗记录审查来验证该队列中发现的意外中风病例。我们将在全队列中检查饮食摄入大豆植物雌激素与总中风风险和中风亚型之间的关系。分析中将使用重复的饮食测量。此外，我们建议在绝经后妇女中进行一项嵌套病例对照研究，以调查缺血性中风(主要的中风类型)与尿中异黄酮类化合物(全身暴露于植物雌激素的生物标志物)水平以及血液中雌二醇、雌酮、睾酮和性激素结合球蛋白水平之间的关系。我们将纳入1500例缺血性卒中病例和1500例单独配对的对照组。在基线采集的生物样品中，将使用基于LC-MS的方法来测量异黄酮类和性激素。考虑到SWHS的规模大、设计前瞻性、随访率高、过去十年收集的广泛暴露和疾病结果信息、生物样本的可用性以及独特的研究人群(大豆消费水平高而激素疗法使用率低)，SWHS是解决目标问题的绝佳机会。这项拟议研究的结果将填补我们关于植物雌激素和内源性雌激素暴露在女性中风病因学中的作用的重要知识空白。

DESCRIPTION (provided by applicant): 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.