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

描述（由申请人提供）：在食用植物雌激素含量高的饮食的地区，一些雌激素相关疾病，如乳腺癌和髋部骨折的发病率较低。因此，植物雌激素可能是雌激素拮抗剂（预防癌症）或相对激动剂（预防骨折）。这与体外研究一致：植物雌激素的雌激素性各不相同。植物雌激素也可能通过非雌激素途径起作用。测量植物雌激素暴露（饮食或血清）并将其与结果联系起来的观察性研究很少。这种研究的缺乏是由于在自由生活人群中研究植物雌激素消耗所固有的挑战，包括：1)获得富含植物营养素的饮食的人的机会有限；2)评估富含植物雌激素的混合菜肴的营养价值是复杂的；3)计算植物雌激素营养值的数据库有限；4)解释植物雌激素代谢能力是困难的。我们提出了一项观察性研究，研究饮食和血清中植物雌激素和植物雌激素代谢物的含量与骨密度（BMD）、血管舒张症状（VMS）、尿失禁（UI）和认知能力之间的关系。我们研究的一个优势是它将解决上述4个挑战中的每一个（详见下文）。目前的研究将利用作为全国妇女健康研究（SWAN）的一部分收集的10多年的暴露和结果数据。SWAN是一个庞大的多种族美国中年女性群体。SWAN已经在3个时间点获得了经过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，并将从这些ffq中估计植物雌激素的摄入量。我们还建议分析来自2个SWAN站点（位于加利福尼亚州）的储存血清样本，选择这些站点是因为它们有高加索人、日本人和中国人的参与者。从与ffq相同的3个时间点储存的血清将用于检测所选的异黄酮和代谢物。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或认知能力有关？膳食植物雌激素对这些结果的影响是否因更年期过渡（MT）阶段而异？在加利福尼亚子样本中，我们将检验血清异黄酮和异黄酮代谢物水平是否与这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：我们提出了一项观察性研究，研究植物雌激素摄入与骨密度、潮热、尿失禁和认知能力这4项对女性健康至关重要的结果之间的关系。这项研究将作为一个转化研究步骤，鼓励或劝阻未来发展基于植物雌激素的干预措施，用于治疗疾病（如潮热）或维持健康（如骨密度保持）。

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).