The Effect of Isoflavone Soy Protein (ISP) Supplementation on Endometrial Thickness, Hyperplasia and Endometrial Cancer Risk in Postmenopausal Women: A Randomized Controlled Trial

Abstract

Soy isoflavones are structurally similar to 17β-estradiol and possess selective estrogen receptor modulator (SERM)-like activity. In postmenopausal women, isoflavone soy protein (ISP) supplementation has been shown to have multiple health benefits, such as reduction of subclinical atherosclerosis when initiated within 5 years of menopause [1]. However, the effect of ISP supplementation on the endometrium has not been studied. To determine whether long term ISP supplementation affects endometrial thickness and rates of endometrial hyperplasia and cancer in postmenopausal women. In this randomized, double-blind, placebo-controlled trial, 350 postmenopausal women 45-92 years of age without diabetes and cardiovascular disease (CVD) were randomized to 2 evenly divided daily doses of 25 g soy protein containing a total of 154 mg of ISP or a milk protein matched placebo for a 3-year period. Participants with a surgically absent uterus were excluded from this analysis. For the remaining 222 participants, ultrasonographic and histopathologic characteristics of the endometrium were compared between intervention and control groups. Compliance with ISP supplementation was confirmed by plasma and urine isoflavone measurements. Endometrial thickness was measured by transvaginal ultrasound at baseline and at 18 and 30 months of follow-up, as well as at 36 months in some participants. The mean change of endometrial thickness from baseline was recorded and compared between treatment groups. Participants with endometrial thickness ≥5 mm and those with vaginal bleeding underwent endometrial biopsies. Incidences of endometrial sampling, endometrial hyperplasia and endometrial cancer were compared between groups. A total of 666 visits among 222 participants were evaluated. There was no statistically significant difference between groups in the baseline endometrial thickness or in changes of endometrial thickness over the trial follow-up (Table 1, p>0.8). Of the 101 placebo-treated participants, 7 (6.9%) underwent an endometrial biopsy; 6 (85.7%) of these biopsies were benign. Of these, 4 were benign, not otherwise specified, and 2 were atrophic. One placebo subject was diagnosed with atypical endometrial hyperplasia and underwent a hysterectomy. The pathology result from this surgery was Stage IB endometrial cancer. Of the 121 participants in the soy group, 9 (7.4%) underwent an endometrial biopsy. The results were benign in all 9 cases (100%). Of these, 5 were benign, not otherwise specified, 3 were atrophic, and 1 proliferative. Although the rate of hyperplasia / malignancy was higher in the placebo group (14.3% versus 0%), the difference was not statistically significant (Table 2). Three-year isoflavone soy protein (ISP) supplementation has no effect on endometrial thickness or on rates of endometrial hyperplasia and cancer in postmenopausal women.