Soy Isoflavones for Menopausal Vasomotor Symptoms

描述(申请人提供)：血管运动症状(VMS)，包括潮热和盗汗，影响大多数更年期妇女。自从妇女健康倡议的结果公布以来，许多妇女和她们的保健提供者不再希望对VMS使用激素疗法。大豆异黄酮类化合物已经上市用于减少VMS，但关于它们的有效性的数据尚不确定。虽然异黄酮在结构上类似于雌激素，因此可以与雌激素受体结合，但大豆食品和补充剂的随机对照试验的结果是混合的。鉴于大豆异黄酮类药物的药代动力学特征，特别是半衰期(约8小时)，给药频率可能对它们降低VMS的有效性至关重要。此外，还没有对VMS的干预研究检查参与者是否为马匹生产者。大豆苷元的活性代谢物木酚可能影响大豆苷元降低VMS强度的作用。我们建议在R21机制下对180名患有中到重度VMS的绝经妇女进行一项小型先导性随机安慰剂对照试验，以检查一系列剂量(每天总剂量为100毫克/天和200毫克/天)和三种剂量频率(每天1次、2次和3次)的胶囊，其中含有大豆中发现的主要异黄酮类化合物(大豆苷元和染料木素)。结果将包括可行性和初步剂量评估。对于可行性目标，我们将：1)评估我们招募和留住参与者的能力；2)衡量遵守胶囊和完成症状日记的情况；3)修改和测试比以前使用的更复杂的每日症状日记；以及4)测试确定Equol生产者状态的可行性和实用性。对于初步的剂量评估目标，我们将检查VMS，因为它们与：1)剂量量和剂量频率的异黄酮类；2)木醇生产者状态；以及3)在一个亚组中，稳态浓度。这些数据将为更大规模、更明确的随机对照试验的最优研究设计、数据收集方法以及每日总剂量和给药频率提供必要的信息。

DESCRIPTION (provided by applicant): Vasomotor symptoms (VMS), including hot flashes and night sweats, affect the majority of menopausal women. Since the results of the Women's Health Initiative were publicized, many women and their health care providers no longer wish to use hormone therapy for VMS. Soy isoflavones have been marketed for reducing VMS, but data are inconclusive as to their effectiveness. Although isoflavones are structurally similar to estrogen and thus bind to estrogen receptors, results from randomized controlled trials of both soy foods and supplements have been mixed. Given the pharmacokinetic characteristics of soy isoflavones, in particular the half-life (approximately 8 hours), dosing frequency may be critical to their effectiveness in reducing VMS. In addition, no intervention study of VMS has examined whether participants are equol producers. Equol, daidzein's active metabolite, may affect the efficacy of daidzein in reducing VMS intensity. We propose to conduct a small pilot randomized placebo-controlled trial under the R21 mechanism of 180 menopausal women with moderate to severe VMS to examine a range of doses (total daily dose of 100 mg/day and 200 mg/day) and three dosing frequencies (1, 2, and 3 times a day) of capsules containing the primary isoflavones found in soy (daidzein and genistein). Outcomes will include feasibility and preliminary dose evaluation. For feasibility aims we will: 1) assess our ability to recruit and retain participants; 2) measure adherence to capsules and to completing symptoms diaries; 3) modify and test a daily symptoms diary that is more complex than previously used; and 4) test the feasibility and utility of identifying equol producer status. For preliminary dose evaluation aims we will examine VMS as they relate to: 1) isoflavones by dose amount and dose frequency; 2) equol producer status; and 3) in a subgroup, steady state concentrations. These data will provide essential information for optimal study design, methods of data collection, and total daily dose and dosing frequency for a larger, more definitive randomized controlled trial.