Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study

Objective: To determine the effects of 5 years of treatment with soy phytoestrogens on histological characteristics of endometrium in postmenopausal women. Design: Randomized, double-blind, placebo-controlled study. Setting: Centre of Perinatal and Reproductive Medicine, Department of Gynecological, Obstetrical, and Pediatric Sciences, University of Perugia, Italy. Patient(s): Three hundred seventy-six postmenopausal healthy women, all with intact uterus. Intervention(s): Women were distributed in two different groups using randomized criteria: group A (n 179) patients received soy tablets (150 mg of isoflavones per day) for 5 years; group B (n = 197) patients received identical appearing placebo tablets for 5 years. Main Outcome Measure(s): Results of endometrial histology from biopsies obtained at baseline, 30 months, and 5 years after the beginning of the treatment. Result(s): Two hundred ninety-eight women completed the 5-year treatment. No cases of malignancy were detected during biopsy. Seventy percent of women undergoing treatment with soy phytoestrogens had an endometrium classified as atrophic or nonassessable versus 81% receiving placebo. The occurrence of endometrial hyperplasia was significantly higher in group A (3.37% vs. 0%). Conclusion(s): Long-term treatment (up to 5 years) with soy phytoestrogens was associated with an increased occurrence of endometrial hyperplasia. These findings call into question the long-term safety of phytoestrogens with regard to the endometrium. (C) 2004 by American Society for Reproductive Medicine.