Dietary and serum phytoestrogens and women's health conditions in midlife

描述(申请人提供)：一些雌激素相关疾病，如乳腺癌和髋部骨折，在食用高植物雌激素饮食的地区发病率较低。因此，植物雌激素可以是雌激素拮抗剂(预防癌症)或相关激动剂(预防骨折)。这与体外研究一致：植物雌激素具有不同的雌激素活性。植物雌激素也可能通过非雌激素途径发挥作用。测量植物雌激素暴露(饮食或血清)并将其与结果相关联的观察性研究很少。缺乏研究是由于研究自由生活人口中植物雌激素消费所固有的挑战，包括：1)接触富含植物营养饮食的人的机会有限；2)评估以富含植物雌激素饮食为特征的混合菜肴的营养价值很复杂；3)计算植物雌激素营养值的数据库有限；以及4)很难说明植物雌激素的代谢能力。我们提出了一项关于饮食和血清中植物雌激素和植物雌激素代谢产物的测量与4种结果的关系的观察性研究：骨密度(BMD)、血管运动症状(VMS)、尿失禁(UI)和认知能力。我们研究的一个优点是，它将解决上述四项挑战中的每一项(详见)。目前的研究将利用10多年来收集的暴露和结果数据，作为全国妇女健康研究(SWAN)的一部分。天鹅是一大群美国中年女性的多种族群体。Swan已经在3个时间点获得了特别修改的食物频率问卷(FFQs)；目前的项目将极大地扩展植物雌激素营养数据库，并将估计这些FFQs的植物雌激素摄入量。我们还建议分析两个天鹅地点(在加利福尼亚州)的存储血清样本，之所以选择这些地点，是因为它们容纳了高加索人、日本人和中国人。从与FFQs相同的3个时间点储存的血清，将被检测选定的异黄酮类和代谢物。我们将进行分析以解决以下主要问题：随着时间的推移，饮食中的植物雌激素暴露是否与BMD、VMS、UI或认知表现相关？饮食中的植物雌激素对这些结果的影响是否取决于绝经过渡(MT)阶段？在加利福尼亚州的子样本中，我们将检查血清异黄酮和异黄酮代谢物水平是否与相同的4种结果相关，以及这种关系是否取决于MT分期。在加利福尼亚州的子样本中，我们有独特的机会来确定异黄酮代谢物的存在是否会放大饮食或血清异黄酮的影响。公共卫生相关性：我们建议进行一项观察性研究，研究植物雌激素摄入与4种对女性健康很重要的结果之间的关系：骨密度、潮热、尿失禁和认知能力。这项研究将作为转化性研究步骤，鼓励或阻止以植物雌激素为基础的干预措施的未来发展，用于治疗疾病(例如潮热)或维持健康(例如保持骨密度)。

DESCRIPTION (provided by applicant): Rates of some estrogen-associated diseases, such a breast cancer and hip fracture, are lower in regions where diets high in phytoestrogens are consumed. Thus, phytoestrogens may be estrogen antagonists (cancer prevention) or relative agonists (fracture prevention). This is consistent with in-vitro studies: phytoestrogens vary in estrogenicity. Phytoestrogens may also work through non-estrogen pathways. Observational studies that have measured phytoestrogen exposures (dietary or serum) and related these to outcomes are scant. This paucity of studies is due to the challenges inherent in studying phytoestrogen consumption in free-living populations, including: 1) limited access to persons with diets rich in phyto-nutrients; 2) assessing nutrient values of mixed dishes, which characterize phytoestrogen-rich diets, is complex; 3) databases to compute phytoestrogen nutrient values are limited; and 4) accounting for phytoestrogen metabolic capability is difficult. We propose an observational study of the relations between both dietary & serum measures of phytoestrogens and phytoestrogen metabolites and 4 outcomes: bone mineral density (BMD), vasomotor symptoms (VMS), urinary incontinence (UI) and cognitive performance. A strength of our study is that it will address each of the 4 challenges described above (detailed within). The current study will make use of exposure and outcomes data collected for over 10 years as part of the Study of Women's Health Across the Nation (SWAN). SWAN is a large multi-ethnic cohort of mid-life US women. SWAN has already obtained specially modified food frequency questionnaires (FFQs) at 3 time points; the current project will greatly expand the phytoestrogen nutrient database and will estimate phytoestrogen intakes from these FFQs. We also propose to also analyze stored serum samples from 2 of the SWAN sites (in California), chosen because they house Caucasian, Japanese, and Chinese participants. Stored serum, from the 3 same time points as the FFQs, will be assayed for selected isoflavones & metabolites. We will conduct analyses to address the following major questions: Is dietary phytoestrogen exposure associated with BMD, VMS, UI, or cognitive performance over time? Does the effect of dietary phytoestrogens on these outcomes vary depending on menopause transition (MT) stage? In the California sub-sample, we will examine whether serum levels of isoflavones & isoflavone metabolites are related to the same 4 outcomes and whether the relation depends on MT stage. In the California sub-sample, we have the unique opportunity to determine whether the presence of isoflavone metabolites amplifies the effects of the dietary or serum isoflavones. PUBLIC HEALTH RELEVANCE: We propose an observational study of the relations between plant estrogen consumption and 4 outcomes that are important to the health of women: bone density, hot flashes, urinary incontinence and cognitive performance. This study will serve as a translational research step, either encouraging or dissuading the future development of plant estrogen-based interventions for the treatment of conditions (e.g., hot flashes) or the maintenance of health (e.g., bone density preservation).