Soy Isoflavones for Menopausal Vasomotor Symptoms

描述（由申请人提供）：血管舒缩症状（VMS），包括潮热和盗汗，影响大多数绝经妇女。自从妇女健康倡议的结果被公布以来，许多妇女及其保健提供者不再希望对VMS使用激素疗法。大豆异黄酮已经上市，以减少VMS，但数据不确定其有效性。尽管异黄酮在结构上与雌激素相似，因此与雌激素受体结合，但对大豆食品和补充剂进行的随机对照试验的结果却喜忧参半。鉴于大豆异黄酮的药代动力学特性，特别是半衰期（约8小时），给药频率可能是其减少VMS有效性的关键。此外，没有VMS的干预研究检查参与者是否为雌马酚生产者。大豆黄酮的活性代谢物马酚可能影响大豆黄酮降低VMS强度的效果。我们建议在R21机制下对180名患有中度至重度VMS的绝经妇女进行一项小型随机安慰剂对照试验，以检查含有大豆中发现的主要异黄酮（大豆苷元和染料木黄酮）的胶囊的剂量范围（每日总剂量为100mg /天和200mg /天）和三种给药频率（每天1次、2次和3次）。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)测量胶囊依从性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；4)验证了识别雌马酚生产者身份的可行性和实用性。为了初步的剂量评估目标，我们将检查VMS，因为它们与：1)异黄酮的剂量量和剂量频率；2)雌马酚生产者地位；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佳研究设计、数据收集方法、总日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.