In this randomized, double-blind, placebo-controlled trial, 350 postmenopausal women aged 45 to 92 years were randomized to receive a daily dose of 25 g soy protein providing 99 mg isoflavones or 25 g milk protein for a 3-year period. Women with a surgically absent uterus were excluded from the analysis (final study population, N = 224). A total of 666 visits among 224 participants were evaluated. Treatment groups did not significantly differ on the mean baseline or on-trial changes in endometrial thickness. Of the 103 placebo-treated participants, 7 (6.8%) underwent endometrial biopsy; 6 (85.7%) of these biopsies were benign. One woman in the placebo group was diagnosed with complex endometrial hyperplasia with atypia and underwent hysterectomy. Of the 121 participants in the soy group, 9 (7.4%) underwent endometrial biopsy. The results were benign in all nine cases (100%). Although the rate of hyperplasia/malignancy was higher in the placebo group (14.3% vs 0%), the difference was not statistically significant. These findings show not only that isoflavone exposure does not adversely affect endometrial tissue but illustrates an important difference between isoflavones and estrogen, wherein the latter increases endometrial thickness and endometrial cancer risk.
Quaas et al. Menopause. 2013.