Genistein aglycone: A new therapeutic approach to reduce endometrial hyperplasia

Abstract Objective Endometrial hyperplasia without cytological atypia is commonly treated with progestins, but other treatment regimes may be available with equivalent efficacy and low side effects. Design A randomized double-blind, placebo and progesterone-controlled clinical trial to evaluate the effects of genistein aglycone in reducing endometrial hyperplasia. Patients A group of 56 premenopausal women with non-atypical endometrial hyperplasia were enrolled and received: genistein aglycone ( n  = 19; 54 mg/day); norethisterone acetate ( n  = 19; 10 mg/day on days 16–25 of the menstrual cycle) or placebo ( n  = 18) for 6 months. Measurements Hysteroscopy was performed with biopsies and symptomology assessed at baseline, 3 and 6 months of administration. The effect on estrogen (ER) and progesterone receptors (PR) expression in uterine biopsies were assessed after 3 and 6 months. For each treatment follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), sex hormone-binding globulin (SHBG) and progesterone (PG) levels were also evaluated. Results After 6 months, 42% of genistein aglycone-administered subjects had a significant improvement of symptoms (histologically confirmed in the 29%) compared to 47% of norethisterone acetate subjects (histologically confirmed in the 31%), but only 12% in the placebo group with 19% exhibiting worsening symptoms and increased endometrial thickness. No significant differences were noted for hormone levels for any treatment, but immunohistochemical analysis revealed significantly reduced staining for ER-α and PR and enhanced ER-β1 staining in genistein-administered subjects associated with a complete regression of bleeding. Conclusions These results suggest that genistein aglycone might be useful for the management of endometrial hyperplasia without atypia in women that cannot be treated with progestin.