CARDIOVASCULAR BENEFITS OF SOY PHYTOESTROGENS

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PROPOSED PROGRAM: (Adapted from Applicant's Abstract) This PPG continues to be a group of interrelated projects focused primarily on the potential cardiovascular benefits of soy phytoestrogen supplementation/treatment. Potential benefits of soy phytoestrogens (SPEs) for breast and uterus of females and of prostate of males constitute a secondary focus. The research is directed toward males and pre and postmenopausal females. In Project 1, the investigators will intensify their pharmacologic studies of the soy phytoestrogens (SPEs) by addressing four questions: 1. What is the peptide fraction of soy protein that is required for the phytoestrogens (isoflavones) to have their effect on lipid metabolism? 2. Are there differences in the effects of soy phytoestrogen preparations that are predominately genistein or predominately daidzein? 3. What is the relationship between dose of soy phytoestrogens and their metabolic effects? 4. What are the longer term effects of the "optimal" soy treatment? The major objective of Project 2 is to assess the usefulness of soy phytoestrogens in primary cardioprotection of adult male monkeys. Also, the study will address directly whether long-term soy consumption is without adverse effects on the reproductive system, cognition, social and sexual behavior and function and determine if it has favorable effects on the prostate gland. 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. Project 3 is a comprehensive, periclinical study that will determine whether treatment with SPEs inhibits the progression of coronary and carotid artery atherosclerosis and improves coronary artery dilator responses in high risk, subordinate premenopausal monkeys. Furthermore, the study will determine whether SPEs inhibit or potentiate proliferation and estrogenic responses in the endometrium and mammary tissue of premenopausal monkeys, and whether SPEs adversely affect or improve bone development and peak bone mass in these females.