Side effects of phytoestrogens: a meta-analysis of randomized trials.
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.
Department of Obstetrics and Gynecology, Medical University Vienna, Vienna, Austria. clemens.tempfer@meduniwien.ac.at
Clemens B
CB
Tempfer
Georg
G
Froese
Georg
G
Heinze
Eva-Katrin
EK
Bentz
Lukas A
LA
Hefler
Johannes C
JC
Huber
D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D004714:Endometrial Hyperplasia / Q000453:epidemiology / Q000209:etiology; D016889:Endometrial Neoplasms / Q000453:epidemiology / Q000209:etiology; D015914:Estrogen Replacement Therapy / Q000009:adverse effects* / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D015994:Incidence; D048789:Phytoestrogens / Q000627:therapeutic use*; D010936:Plant Extracts; D017698:Postmenopause / Q000187:drug effects*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D014592:Uterine Hemorrhage / Q000453:epidemiology / Q000209:etiology
D048789:Phytoestrogens; D010936:Plant Extracts