The aims of this evidence report are to summarize the current evidence on the health effects of soy and its isoflavones on the following: cardiovascular diseases, menopausal symptoms, endocrine function, cancer, bone health, reproductive health, kidney diseases, cognitive function, and glucose metabolism. In addition, safety issues and drug interactions of using soy and its isoflavones, as reported in the literature, are summarized. This report also summarizes the formulations of soy products and/or soy food used in clinical trials. The report was requested and funded by the National Center for Complementary and Alternative Medicine (NCCAM) and the Office of Dietary Supplements at the National Institutes of Health (NIH) and was conducted through the Evidence-based Practice Center (EPC) program at the Agency for Healthcare Research and Quality (AHRQ). There is increasing interest in soy and health since the U.S. Food and Drug Administration approved a health claim in October 1999 for use on food labels stating that a daily diet containing 25 grams of soy protein, also low in saturated fat and cholesterol, may reduce the risk of heart disease. This claim was based on the beneficial results in reducing plasma low-density lipoprotein (LDL) levels from dozens of human controlled clinical trials. The health claim, however, covers only soy protein, since research results surrounding soy isoflavones were controversial. This report summarizes the current evidence on the health effects of soy and its isoflavones. Five general questions are addressed in this report: 1. In the clinical trial literature, what formulations of soy were used? At what dose? For what purpose(s) (e.g., trial endpoints)? 2. Does current clinical trial evidence indicate that whole soy products and individual constituents of soy have an effect on: a. Cardiovascular events, risk factors, and measures; b. Menopausal symptoms; c. Endocrine function; d. Cancer and tumor-related biomarkers; e. Osteoporosis and osteoporosis risk factors; f. Reproductive health; g. Kidney function; and h. Other outcomes, based on results of Key Question 1, above? 3. What is the scientific evidence of a dose response effect of different forms of soy and individual constituents of soy for the conditions specified in Key Question 1? 4. What are the frequency and type(s) of adverse events associated with consumption of soy that are reported in the scientific literature (both trials and epidemiology)? 5. What is the scientific evidence of a dose-response effect of whole soy products and individual soy constituents on their safety?