Soy Isoflavones for Menopausal Vasomotor Symptoms

描述（由申请人提供）：血管痉挛症状（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，许多妇女及其保健提供者不再希望对VMS使用激素疗法。大豆异黄酮已上市用于减少VMS，但其有效性的数据尚不确定。虽然雌激素在结构上与雌激素相似，因此与雌激素受体结合，但大豆食品和补充剂的随机对照试验结果好坏参半。鉴于大豆异黄酮的药代动力学特征，特别是半衰期（约8小时），给药频率可能对其减少VMS的有效性至关重要。此外，没有VMS干预研究检查参与者是否是雌马酚生产者。大豆黄酮的活性代谢产物雌马酚可能影响大豆黄酮降低VMS强度的功效。我们建议在R21机制下对180名患有中度至重度VMS的绝经期妇女进行一项小型试点随机安慰剂对照试验，以检查一系列剂量（每日总剂量为100 mg/天和200 mg/天）和三种给药频率（每天1次，2次和3次）的胶囊，其中含有大豆中发现的主要黄酮（大豆苷元和染料木黄酮）。结果将包括可行性和初步剂量评估。为了实现可行性目标，我们将：1）评估我们招募和留住参与者的能力; 2）测量对胶囊的坚持和完成症状日记; 3）修改和测试比以前使用的更复杂的每日症状日记;和4）测试识别雌马酚生产者状态的可行性和实用性。对于初步剂量评价目的，我们将检查VMS，因为它们涉及：1）按剂量和给药频率列出的雌马酮; 2）雌马酚生产者状态; 3）亚组中的稳态浓度。这些数据将为更大、更明确的随机对照试验的最佳研究设计、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.