Genistein reduces angiogenesis and apoptosis in women with endometrial hyperplasia

Endometrial hyperplasia without cytological atypia is commonly treated with pro- gestins, but other treatments may be available with equivalent efficacy and reduced side effects. Here, we evaluate the effect of genistein aglycone on angiogenesis and apoptosis-related markers women with endometrial hyperplasia. Premenopausals (n=38) with nonatypical endometrial hyperplasia were administered either genistein aglycone (54 mg/day, n=19) or norethisterone acetate (10 mg/day, n=19) on days 16-25 of the menstrual cycle and evaluated for 6 months. Biopsies were taken during hysteroscopy at baseline and 6 months, and symptoms including excessive uterine bleeding were assessed at baseline and 3 and 6 months following recruitment. The expression of angiogenesis (Vegf), epithelial (Egf and Tgfb), and apoptosis-related (Bax, Bcl-2, and Casp-9) molecules, were assessed in uterine biopsies at baseline and after 6 months of therapy. Follicle-stimulating hormone, luteinizing hormone, estradiol, SHBG, and progesterone levels were also measured. After 6 months, 42% of genistein aglycone-administered patients had a significant improvement of symptoms compared to 47% of norethisterone acetate subjects. No significant differences were noted in hormone levels for any treatment. Gene expression revealed a significant reduction in Vegf , Egf, and Tgfb (P,0.05 versus baseline), and an increase in proapoptotic molecules (Bax and Casp-9), with a concomitant decrease in Bcl-2 values (P,0.05) in both groups. These results suggest that genistein aglycone might be useful for the management of endometrial hyperplasia without atypia in women who cannot or do not wish to be treated with progestin.