Phytoestrogens and Progression of Atherosclerosis

描述(申请人提供)：对传统激素替代疗法(HRT)的恐惧和不满，加上对天然产品的兴趣，导致妇女和她们的医生都越来越多地使用大豆蛋白作为绝经后治疗的替代方案。来自流行病学和非人类灵长类动物研究的证据表明，富含异黄酮类的大豆蛋白具有抗动脉粥样硬化活性，这一证据得到了大量数据的支持，这些数据表明了机理和生物学上的合理性。据我们所知，还没有发表或提出研究来确定大豆蛋白对绝经后女性动脉粥样硬化进展的长期影响。我们建议在300名没有心血管疾病临床证据的健康绝经后妇女中进行一项为期2.5年的富含异黄酮类大豆蛋白的随机、双盲、安慰剂对照试验。我们假设，相对于安慰剂，富含异黄酮类的大豆蛋白(提供染料木素、大豆苷元和大豆黄素)将减少健康绝经后女性亚临床动脉粥样硬化的进展。主要终点将是亚临床动脉粥样硬化的进展，以计算机图像处理的B型超声图像中颈总动脉内中膜厚度的变化率来衡量，是抗动脉粥样硬化试验的公认的非侵入性动脉成像终点，富含异黄酮类的大豆蛋白可能提供一种安全有效的替代方法，将内源性雌激素提供的绝经前心脏保护延长到更年期，而不会增加血栓栓塞事件和与传统HRT相关的某些癌症的风险。由于许多绝经后妇女使用大豆产品来维持健康，了解大豆蛋白是否具有抗动脉粥样硬化作用很重要，以便妇女能够就她们对这种形式的绝经后治疗的期望做出真正知情的决定。大豆蛋白在减少绝经后妇女动脉粥样硬化进展方面是否有效的问题不仅是及时的，而且具有巨大的医学和财务重要性，因为动脉粥样硬化仍然是绝经后妇女的头号杀手。

DESCRIPTION (provided by applicant): The fear and discontent with traditional hormone replacement therapy (HRT) coupled with the interest in natural products has resulted in an increased use of soy protein as a postmenopausal therapeutic alternative by both women and their physicians alike. Evidence from epidemiological and non-human primate studies indicate that isoflavone-rich soy protein has antiatherogenic activity, evidence supported by a large body of data that indicate mechanistic and biologic plausibility. No studies to our knowledge have been published or proposed to determine the long-term effects of soy protein on the progression of atherosclerosis in postmenopausal women. We propose to conduct a 2.5-year, randomized, double-blind, placebo-controlled trial of isoflavone-rich soy protein in 300 healthy postmenopausal women without clinical evidence of cardiovascular disease. We hypothesize that relative to placebo, isoflavone-rich soy protein (supplying genistein, daidzein and glycitein) will reduce the progression of subclinical atherosclerosis in healthy postmenopausal women. The primary end point will be the progression of subclinical atherosclerosis measured as the rate of change in common carotid artery intima-media thickness in computer image processed B-mode ultrasonograms, a well-established noninvasive arterial imaging end point for antiatherosclerosis trials, lsoflavone-rich soy protein may provide a safe and effective alternative approach for extending premenopausal cardioprotection afforded by endogenous estrogen into menopause without the increased risk of thromboembolic events and certain cancers associated with traditional HRT. Since many postmenopausal women are using soy products to maintain their health, it is important to understand whether soy protein has an antiatherogenic effect so that women can make a truly informed decision concerning their expectations of this form of postmenopausal therapy. The question as to whether soy protein is effective in reducing the progression of atherosclerosis in postmenopausal women is not only timely, but also of immense medical and financial importance since atherosclerosis remains the number I killer of postmenopausal women.