Two hundred ninety-eight healthy postmenopausal women (mean age, 50 years) were randomly assigned to receive, in double-blind fashion, tablets providing 150 mg/day of soy isoflavones or placebo for 5 years. Endometrial biopsies were performed at baseline and after 30 months and 5 years. No cases of endometrial hyperplasia were detected after 30 months. After 5 years, of 154 women who received soy isoflavones, 6 (3.9%) were found to have endometrial hyperplasia (5 simple, 1 complex hyperplasia), compared with none of the women receiving placebo (p < 0.05). No cases of endometrial cancer were detected.

Comment: Because soy isoflavones have weak estrogenic effects, the authors of this study hypothesized that supplementation with soy isoflavones might have a proliferative effect on the endometrium. Although the incidence of endometrial hyperplasia was far less than that induced by treatment with unopposed estrogens, isoflavone supplementation was not entirely innocuous, as nearly one in 25 women developed hyperplasia. The dose of soy isoflavones used in this study was approximately two to three times the amount used in most research. Nevertheless, the possibility exists that long-term use of isoflavones could cause uterine hyperplasia, and women taking soy isoflavones should be monitored appropriately.

Unfer V, et al. Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study. Fertil Steril 2004;82:145-148.