PHARMACOLOGIC STUDIES OF SOY PHYTOESTROGENS

我们已经获得了实验证据来支持大豆植物雌激素可能是传统激素替代疗法的有用替代品的结论。我们还从一项对年轻食蟹雄性的研究中得到证据，表明大豆植物雌激素可能具有心脏保护作用，并且它们不会影响青春期前和青春期周围雄性的生殖系统。我们对绝经后女性和大豆植物雌激素的关注提高了我们对大豆植物雌激素同时对冠心病和激素依赖性癌症的潜在保护作用的公共卫生重要性的认识。这使我们开始探索一种可能性，即给男性服用大豆植物雌激素可能具有心脏保护作用，对生殖系统没有不利影响，并可能提供预防前列腺癌的保护。我们建议加强大豆植物雌激素的药理学研究。我们将在本研究中使用绝经后女性和男性，以评估治疗对男女心血管系统和生殖系统的影响以及女性骨代谢生物标志物。本研究将使用6组5只手术绝经的雌性猴子和6组5只成熟的雄性猴子进行一系列短期拉丁广场设计。这些研究将评估不同剂量、形式和比例的植物雌激素对中间结果的影响。本项目需要解决的具体问题如下：大豆蛋白中异黄酮对脂质代谢产生影响所需的肽部分是多少？我们将测试大豆蛋白的高分子量部分或7S肽是否需要异黄酮有效。以染料木素为主或以大豆黄酮为主的大豆植物雌激素制剂在结果上有差异吗？大豆植物雌激素（SPE）的剂量与结果有什么关系？

We have obtained experimental evidence to support the conclusion that soy phytoestrogens may be a useful alternative to traditional hormone replacement therapy for females. We also have evidence from a study in young cynomolgus males that the soy phytoestrogens may be cardioprotective and that they do not affect the reproductive system of pre- and peripubertal males. Our concentration on postmenopausal females and soy phytoestrogens has increased our awareness of the public health importance of the simultaneous potential protective effects of soy phytoestrogens on coronary heart disease and hormone dependent cancers. That has caused us to pursue the possibility that soy phytoestrogens given to males will be cardioprotective, have no adverse effects on the reproductive system, and may provide protection against prostate cancer. We propose to intensify our pharmacologic studies of the soy phytoestrogens. We will use both postmenopausal females and males in this study in order to assess treatment effects on the cardiovascular system and reproductive system of both genders and bone metabolism biomarkers in females. This study will utilize 6 groups of 5 surgically menopausal female monkeys and 6 groups of 5 mature male monkeys assigned to a series of short-term Latin Square designs. The studies will assess the effects of varying doses, forms, and ratios of the phytoestrogens on intermediate outcomes. The specific questions to be addressed in this project are as follow: What is the peptide fraction in soy protein that is required for the isoflavones to have their effect on lipid metabolism? We will test whether the high molecular weight fraction or the 7S peptides of soy protein are required for the isoflavones to be effective. Are there differences on outcomes with soy phytoestrogen preparations that are predominately genistein or predominately daidzein? What is the relationship between dose of soy phytoestrogens (SPE) and outcomes?