EFFECTS OF SOY ON MALE MONKEYS

（改编自申请人摘要）目前还没有一种男性冠心病预防方法能兼具安全性、有效性、广泛接受性和低成本的特点。而“他汀类”化合物，例如，洛伐他汀，普伐他汀，在预防冠状动脉事件方面是有效的，但是存在关于副作用、依从性和成本的问题，这些问题限制了它们的使用。 大豆植物雌激素可能是预防冠心病的药物手段的替代品。 有有限的证据表明，大豆消费抑制动脉粥样硬化形成，并对冠状动脉血管反应性有有利的影响，而对其他器官系统有有利或中性的影响。项目2的主要目的是评估大豆植物雌激素在成年雄性猴的初级心脏保护中的有用性。 该研究将直接解决长期食用大豆是否对生殖系统，认知，社会或性行为和功能没有不利影响，并确定它是否对前列腺有有利影响。 将90只食蟹猴随机分为三个治疗组：1）安慰剂致动脉粥样硬化饮食（n=30），2）低植物雌激素致动脉粥样硬化饮食（58 mg/1800 Cal）（n=30）和3）高植物雌激素致动脉粥样硬化饮食（120 mg/1800 Cal）（n=30）。 饮食在致动脉粥样硬化性和营养成分方面是相同的，它们的区别仅在于植物雌激素含量。 在36个月的治疗期间，将对血浆脂蛋白、血压、动脉血管功能、社会性功能、睾丸内分泌和生精功能以及认知功能进行评估。 将对动脉粥样硬化程度和雌激素受体（α和β）的动脉表达进行尸检评估。 此外，还将研究前列腺增生和肿瘤的免疫组织化学和组织形态计量学标志物，以及乳腺增生和肿瘤的组织形态计量学标志物。 还将评估精子发生。 最后，将对中枢神经系统中雌激素刺激的行为相关免疫组织化学标志物进行评估。 由于目前关于大豆对心血管、生殖和中枢神经系统影响的数据非常有限，因此这项研究是阐明男性广泛食用大豆对公共健康产生有利影响的潜力的必要步骤。

(Adapted from Applicant's Abstract) There is no means of coronary heart disease prevention for men that combines the qualities of safety, effectiveness, wide acceptability and low cost. While the "statin" group of compounds, e.g., lovastatin, pravastatin, is effective in preventing coronary events, there are issues regarding side effects, compliance and cost that limit their use. Soy phytoestrogens may represent an alternative to pharmacologic means of coronary heart disease prevention. There is limited evidence indicating that soy consumption inhibits atherogenesis and has favorable effects on coronary vascular reactivity while having favorable or neutral effects on other organ systems. The major objective of Project 2 is to assess the usefulness of soy phytoestrogens in primary cardioprotection of adult male monkeys. The study will address directly whether long-term soy consumption is without adverse effects on the reproductive system, cognition, social or sexual behavior and function and determine if it has favorable effects on the prostate gland. Ninety cynomolgus monkeys will be randomized to three treatment groups: 1) placebo atherogenic diet (n=30), 2) low phytoestrogen atherogenic diet (58 mg/1800 Cal) (n=30) and 3) high phytoestrogen atherogenic diet (120 mg/1800 Cal) (n=30). Diets are identical in atherogenicity and nutritional content; they differ only in phytoestrogen content. During a 36 month treatment period, assessments will be made of plasma lipoproteins, blood pressure, arterial vasomotor function, sociosexual function, testicular endocrine and spermatogenic function, and cognitive function. Postmortem assessments will be made of atherosclerosis extent and arterial expression of estrogen receptors (alpha and beta). In addition, immunohistochemical and histomorphometric markers of prostatic hyperplasia and neoplasia will be studied as will histomorphometric markers of mammary gland hyperplasia and neoplasia. Spermatogenesis will also be assessed. Finally, assessments will be made of behavior-relevant immunohistochemical markers of estrogenic stimulation in the central nervous system. Since the body of data that exists currently regarding the effects of soy on the cardiovascular, reproductive, and central nervous systems is quite limited, this study represents a necessary step in elucidating the potential for a favorable public health impact of widespread soy consumption by men.