PHARMACOLOGIC STUDIES OF SOY PHYTOESTROGENS

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(Adapted from Applicant's Abstract) During the last program project period, the investigators obtained experimental evidence to support the conclusion that soy phytoestrogens (isoflavones) may be a useful alternative to traditional hormone replacement therapy for females, protecting against atherosclerosis without deleterious effects on the breast and endometrium. The investigators also found in a study with pre- and peripubertal cynomolgus males that the soy isoflavones were cardioprotective and did not affect the reproductive system. These studies increased the investigators' awareness of the public health importance of the simultaneous potential protective effects against coronary heart disease and hormone dependent cancers. In Project 1, the investigators propose to intensify their pharmacologic studies of the soy phytoestrogens using surgically menopausal female and mature male monkeys in a series of short-term Latin Square designs to assess the effects of varying doses, forms, and ratios of the phytoestrogens on intermediate outcomes (Aims 1, 2, 3). Aim 4 will be a longer-term comparison of "optimal" (best protein, isoflavone ratio, and dose) and control treatments. This project will assess treatment effects on cardiovascular disease risk factors and reproductive system of both genders and bone endpoints in females. The questions to be addressed are: 1. Is the high molecular weight fraction or the 7S peptide component in soy protein more effective than soy protein isolate on improving lipid metabolism and is one of these fractions required for the isoflavones to have their effect? 2. Are there different effects on disease markers with soy phytoestrogen preparations that are predominately genistein or predominately daidzein? 3. What is the relationship between dose of soy phytoestrogens and disease markers? 4. What are the longer-term effects of the optimal soy treatment on disease markers? This project relates directly to the central theme of the program project, specifically, to better understand the cardioprotective benefits of the soy phytoestrogens. The data to be obtained in this project should contribute to the understanding of data obtained in Projects 2 and 3 while Projects 2 and 3 will provide pathologic outcomes to support the intermediate endpoints used in this project.