The principal investigator, responding to topic #5, "alternatives to estrogen therapy", is a new investigator. Phytoestrogens are natural estrogens found in plants. Asian populations eat large amounts of soy products containing the phytoestrogens isoflavones, and have a lower incidence of osteoporosis, heart disease, breast cancer, as well as menopausal symptoms. It has been proposed that the Asian populations' high dietary phytoestrogens explains this lower risk of these "estrogen- deprivation" disorders. The mechanism of phytoestrogens may be similar to that of Tamoxifen, a medication used to treat breast cancer. Phytoestrogens are structurally similar to Tamoxifen and like Tamoxifen may function as mixed agonists/antagonists. Tamoxifen is associated with an increased risk of endometrial cancer, secondary to estrogenic effects upon endometrium. If phytoestrogens function like Tamoxifen, patients supplementing their diet with phytoestrogens may be at risk for endometrial cancer. This may be especially relevant to a Western population with risk factors for endometrial cancer (e.g., obesity) not as prevalent in the Asian population. In this study, I propose to assess the estrogenic effects of phytoestrogens, at a concentration sufficient to reduce menopausal symptoms, on the endometrium of postmenopausal women. Specific aims are to examine the effects of six months of phytoestrogen ingestion (soy dietary supplementation) on endometrial histology assessed endometrial biopsy, to evaluate efficacy to reduce menopausal symptomatology and side effects. The experimental design is double-blind, prospective, randomized, and placebo-controlled. Baseline endometrial biopsies will be performed on post-menopausal women currently not taking hormone replacement therapy. After biopsy, patients with adequate endometrial biopsies without evidence of hyperplasia, cancer, or ovulation will be randomized to receive either a soy (as phytoestrogen source) or wheat cereal (placebo) for six months. The soy cereal provides 100 mg of isoflavones, an amount which has been shown to relieve menopausal symptoms. At the end of the supplementation period, a repeat endometrial biopsy will be performed. The percentage of patients with evidence of estrogen effect will be compared to the percentage with estrogenic histological changes in the baseline biopsy. I have selected a sample size (n=26 in each group) sufficient (p<0.05, power=0.8) to detect a 2.5 fold increase in the percentage of patients with estrogenic stimulation to the endometrium and increase which I propose would warrant additional long-term