Long-term endometrial and breast safety of a specific, standardized soy extract

Abstract

Objective To assess the effects of an oral soy isoflavone extract (Phytosoya®) on endometrium and breast in postmenopausal women treated for 3 years.

Methods A total of 395 postmenopausal women were included in this international prospective, open-label study. The number of patients who completed the 3-year study was 197. The women were treated for 3 years with a specific, standardized soy isoflavone extract (total 70 mg/day). Endometrial biopsy, transvaginal ultrasonography and mammography were performed before and after 3 years of treatment.

Results No case of hyperplasia/cancer was diagnosed among the 192 interpretable biopsies at 3 years. Only one case of simple hyperplasia was diagnosed among 197 post-baseline interpretable biopsies. The endometrial safety of this extract has been demonstrated (point estimate 0.5%). There was no statistically significant change in endometrial thickness after 3 years (98.4% inactive or atrophic and 0.3% proliferative endometrium at 1 year). Mammography results showed no notable change from baseline. No patient in any set developed an ACR classification of 4 or 5 after 3 years of treatment. The global safety was rated as either ‘excellent’ or ‘good’ by 99.1% of investigators and 99.0% of patients after 3 years of treatment. The adverse events were as follows: eight patients had metrorrhagia and seven patients had at least one breast adverse event: three patients had ‘breast pain’, two patients reported ‘breast tenderness’ and two patients had ‘hypertrophic breast’ (most of them were possibly treatment-related).

Conclusions As no case of hyperplasia was diagnosed among the 301 interpretable biopsies at 1 year and there was only one case of simple hyperplasia in the 197 post-baseline biopsies at 3 years, the endometrial safety of this extract has been demonstrated. Furthermore, as demonstrated by the lack of change in endometrial thickness associated with the histologic results, we suggest that this extract does not exert a mitogenic effect on the endometrium. These results suggest that daily administration of 70 mg of a specific, standardized isoflavone extract for 3 years could be a safe treatment for both endometrium and breast.

Key words:

• MENOPAUSE
• ENDOMETRIUM
• ENDOMETRIAL HYPERPLASIA
• BREAST
• MAMMOGRAPHIC BREAST DENSITY
• SOY ISOFLAVONE EXTRACT

Conflict of interest  S. Palacios has been a symposium speaker or advisory board member for several companies, including Bayer-Schering, Novo Nordisk, Servier, Lilly, Daiichi-Sankyo, Sanofi-Aventis, MSD and Procter and Gamble. He also receives research grants and/or consulting fees from the following companies: Wyeth, Servier, Lilly, Daiichi-Sankyo, Amgen, Arkochim and Bayer-Schering. L. Aubert, at the time of the clinical trial, was Clinical Project Manager at Arkopharma Laboratories; P. Chantre, at the time of the clinical trial, was Head of Clinical Development at Arkopharma Laboratories; B. Pornel, F. Vázquez and P. Marès declare no conflict of interest.

Source of funding  This work was supported by Arkopharma Pharmaceutical Laboratories.