Genistein aglycone: a new therapeutic approach to reduce endometrial hyperplasia

Phytomedicine. 2010 Sep;17(11):844-50. doi: 10.1016/j.phymed.2010.03.024. Epub 2010 May 31.


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-alpha and PR and enhanced ER-beta1 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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Contraceptives, Oral, Synthetic / pharmacology
  • Contraceptives, Oral, Synthetic / therapeutic use*
  • Double-Blind Method
  • Endometrial Hyperplasia / drug therapy*
  • Endometrial Hyperplasia / pathology
  • Endometrium / drug effects
  • Endometrium / pathology
  • Female
  • Genistein / analogs & derivatives
  • Genistein / pharmacology
  • Genistein / therapeutic use*
  • Humans
  • Middle Aged
  • Norethindrone / analogs & derivatives*
  • Norethindrone / pharmacology
  • Norethindrone / therapeutic use
  • Norethindrone Acetate
  • Phytoestrogens / pharmacology
  • Phytoestrogens / therapeutic use*
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Premenopause
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Uterine Hemorrhage / drug therapy


  • Contraceptives, Oral, Synthetic
  • Phytoestrogens
  • Plant Extracts
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Norethindrone Acetate
  • Genistein
  • Norethindrone