Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study.
OBJECTIVE
To determine the effects of 5 years of treatment with soy phytoestrogens on histological characteristics of endometrium in postmenopausal women.


METHODS
Randomized, double-blind, placebo-controlled study.


METHODS
Centre of Perinatal and Reproductive Medicine, Department of Gynecological, Obstetrical, and Pediatric Sciences, University of Perugia, Italy.


METHODS
Three hundred seventy-six postmenopausal healthy women, all with intact uterus.


METHODS
Women were distributed in two different groups using randomized criteria: group A (n = 179) patients received soy tablets (150 mg of isoflavones per day) for 5 years; group B (n = 197) patients received identical appearing placebo tablets for 5 years.


METHODS
Results of endometrial histology from biopsies obtained at baseline, 30 months, and 5 years after the beginning of the treatment.


RESULTS
Two hundred ninety-eight women completed the 5-year treatment. No cases of malignancy were detected during biopsy. Seventy percent of women undergoing treatment with soy phytoestrogens had an endometrium classified as atrophic or nonassessable versus 81% receiving placebo. The occurrence of endometrial hyperplasia was significantly higher in group A (3.37% vs. 0%).


CONCLUSIONS
Long-term treatment (up to 5 years) with soy phytoestrogens was associated with an increased occurrence of endometrial hyperplasia. These findings call into question the long-term safety of phytoestrogens with regard to the endometrium.
Unfer
Vittorio
V
AGUNCO, Obstetrics and Gynecology Centre, Rome, Italy. vittorio.unfer@lycos.com
Casini
Maria Luisa
ML
Costabile
Loredana
L
Mignosa
Marcella
M
Gerli
Sandro
S
Di Renzo
Gian Carlo
GC
D001706:Biopsy; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology*; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007529:Isoflavones / Q000008:administration & dosage / Q000009:adverse effects* / Q000302:isolation & purification; D008875:Middle Aged; D048789:Phytoestrogens; D010919:Placebos; D028321:Plant Preparations / Q000008:administration & dosage / Q000009:adverse effects*; D017698:Postmenopause; D013025:Glycine max / Q000737:chemistry*
D007529:Isoflavones; D048789:Phytoestrogens; D010919:Placebos; D028321:Plant Preparations