EFFECTS OF SOY ON MALE MONKEYS

(摘自申请者摘要)目前还没有一种集安全、有效、广泛接受和低成本为一体的男性冠心病预防方法。虽然“他汀类”化合物，如洛伐他汀、普伐他汀，在预防冠状动脉事件方面是有效的，但副作用、依从性和成本等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理手段的替代方法。有限的证据表明，食用大豆抑制动脉粥样硬化的形成，对冠状动脉血管的反应性有有利的影响，同时对其他器官系统有有利的或中性的影响。项目2的主要目标是评估大豆植物雌激素在成年雄性猴子初级心脏保护中的有效性。这项研究将直接研究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3组：安慰剂组(n=30)、低植物雌激素组(58 mg/1800Cal)和高植物雌激素组(120 mg/1800Cal)(n=30)。饮食在致动脉粥样硬化和营养含量方面是相同的；它们只在植物雌激素含量上有所不同。在36个月的治疗期间，将对血浆脂蛋白、血压、动脉血管舒缩功能、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动脉雌激素受体(α和β)的表达进行尸检评估。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记物以及乳腺增生症和肿瘤的组织形态计量学标记物。还将对精子发生进行评估。最后，将对中枢神经系统雌激素刺激的行为相关免疫组织化学标记物进行评估。由于目前存在的关于大豆对心血管、生殖和中枢神经系统的影响的数据非常有限，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可能性的必要步骤。

(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.