Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study

Received 14 July 2003; received in revised form 12 November 2003; accepted 12 November 2003.

Abstract

Objective

To determine the effects of 5 years of treatment with soy phytoestrogens on histological characteristics of endometrium in postmenopausal women.

Design

Randomized, double-blind, placebo-controlled study.

Setting

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

Patient(s)

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

Intervention(s)

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.

Main outcome measure(s)

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

Result(s)

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%).

Conclusion(s)

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.

Keywords: Phytoestrogens, endometrial effects, postmenopausal therapy

a A.G.UN.CO., Obstetrics and Gynecology Centre, Rome, Italy

b Department of Human Physiology and Pharmacology “Vittorio Erspamer,” University “La Sapienza,” Rome, Italy

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

Reprint requests: Prof. Vittorio Unfer, A.G.UN.CO. Obstetrics and Gynecology Centre, Via G. Cassiani, 15-00155 Rome, Italy (FAX: 39-06-3241284).

PII: S0015-0282(04)00530-8

doi:10.1016/j.fertnstert.2003.11.041

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