Side Effects of Phytoestrogens: A Meta-analysis of Randomized Trials
Abstract
Background
Phytoestrogens are widely used by postmenopausal women for the treatment of the climacteric syndrome. The risk of adverse effects of this treatment, however, is unknown.
Methods
Using a fixed-effects model, we performed a meta-analysis of side effects comparing phytoestrogen treatment with placebo or no treatment in randomized controlled trials.
Results
We identified 174 randomized controlled trials. Side effects were reported in 92/174 randomized controlled trials with 9629 participants. The overall incidence of side effects in the phytoestrogen and control groups was 2019/5502 (36.7%) and 1824/4806 (38.0%), respectively (P=.2; incidence rate ratio [IRR] 1.01; 95% confidence interval [CI], 0.95-1.08). Comparing various side effect categories, we found significantly higher rates of gastrointestinal side effects among phytoestrogen users (P=.003; IRR 1.28; 95% CI, 1.08-1.50). Gynecological (IRR 0.94; 95% CI, 0.74-1.20), musculoskeletal (IRR 1.20; 95% CI, 0.94-1.53), neurological (IRR 0.91; 95% CI, 0.70-1.19), and unspecific side effects (IRR 0.95; 95% CI, 0.88-1.03) were not significantly different between groups. Within side effect categories, we found no significantly higher rates of side effects in women using phytoestrogens. Specifically, the rates of hormone-related side effects such as endometrial hyperplasia, endometrial cancer, and breast cancer were not significantly different between groups.
Conclusions
Based on the available evidence, phytoestrogen supplements have a safe side-effect profile with moderately elevated rates of gastrointestinal side effects. Rates of vaginal bleeding, endometrial hyperplasia, endometrial cancer, and breast cancer were not significantly increased among phytoestrogen users in the investigated studies.
aDepartment of Obstetrics and Gynecology, Medical University Vienna, Austria
bDepartment of Medical Statistics, Medical University Vienna, Austria
Requests for reprints should be addressed to Clemens Tempfer, MD, Department of Obstetrics & Gynecology; Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna/Austria
Funding: None.
Conflict of Interest: Authors CBT and JCH received lecture fees by Apomedica Inc. All other authors report no conflict of interest.
Authorship: All authors had access to the data and a role in writing the manuscript.
ABSTRACT
