Soy Isoflavones for Reducing Bone Loss Study

Abstract

Objectives To assess the overall safety and potential endometrial stimulation of soy isoflavone tablets consumed (3-year) by postmenopausal women. To determine the endometrial thickness response-to-treatment among compliant women, taking into account hormone concentrations and other hypothesized modifying factors. Methods We randomized healthy postmenopausal women (45.8–65.0 years) to placebo control or two doses (80 or 120 mg/day) of soy isoflavones at two sites. We used intent-to-treat (N=224) and compliant (>95%; N=208) analyses to assess circulating hormone concentrations, adverse events, and endometrial thickness (via transvaginal ultrasound). Results Median values for endometrial thickness (mm) declined from baseline through 36 mo. Nonparametric ANOVA for treatment differences among groups showed no differences in absolute (or percentage change) endometrial thickness at any time point (Chi-Square p-values ranged from 0.12–0.69), nor in circulating hormones at any time point. A greater number of adverse events for the genitourinary system (p=0.005) was noted in the 80 compared to 120 mg/day group, whereas other systems showed no treatment effects. The model predicting the endometrial thickness response-(using natural logarithm)-to-treatment with compliant women across time points was significant (p<0.0001), indicating that estrogen exposure (p=0.0013), plasma 17 β-estradiol (p=0.0086), and alcohol intake (p=0.023) contributed significantly to the response. Neither the 80 (p=0.57) nor 120 (p=0.43) mg/day dose exerted an effect on endometrial thickness across time. Conclusions Our RCT verified the long-term overall safety of consuming soy isoflavone tablets by postmenopausal women who displayed excellent compliance. We found no evidence of a treatment effect on endometrial thickness, adverse events, or circulating hormone concentrations, most notably thyroid function, during a three year period.

The association between soya consumption and serum thyroid-stimulating hormone concentrations in the Adventist Health Study-2

“…Likewise, in a 3-year study, postmenopausal women given 80 or 120 mg of soya isoflavones daily showed no changes in thyroid function (32) . The authors of these recent publications have concluded that genistein and probably other isoflavones appear to show a good profile of safety in regard to thyroid function (33) .…”

Oral isoflavone supplementation on endometrial thickness: a meta-analysis of randomized placebo-controlled trials

“…There have been many studies shown that given isoflavone product to postmenopausal women might relieve menopausal symptoms such as hot flushes and vaginal dryness [ 8 , 9 ]. There are also studies evaluated the effect of oral isoflavone supplementation on endometrial thickness, a risk factor of endometrial cancer [ 10 - 32 ]. However, the results were not consistent, and the sample sizes were relatively small (vary from 15 to 401).…”

Soy and Health Update: Evaluation of the Clinical and Epidemiologic Literature

“…A comprehensive review published in 2006 that included 14 clinical trials found that the totality of the evidence showed that neither soyfoods nor isoflavones adversely affect thyroid function in euthyroid men or women [402]. Studies published since this review [403,404,405,406,407], which include two that were three years in duration [408,409], are supportive of this conclusion as is the conclusion of the EFSA that isoflavone supplements do not affect thyroid function in postmenopausal women [108]. …”