Genistein aglycone: A new therapeutic approach to reduce endometrial hyperplasia

Bitto, Alessandra; Granese, Roberta; Triolo, Onofrio; Villari, Daniela; Maisano, Daniele; Giordano, Domenico; Altavilla, Domenica; Marini, Herbert; Adamo, Elena Bianca; Nicotina, Piero Antonio; D’Anna, Rosario; Squadrito, Francesco

doi:10.1016/j.phymed.2010.03.024

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Volume 17, Issue 11 , Pages 844-850, September 2010

Genistein aglycone: A new therapeutic approach to reduce endometrial hyperplasia

Alessandra Bitto
- Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria, Gazzi, 98125, Messina, Italy
- AB and RG equally contributed to this paper.
Roberta Granese
- Department of Obstetrical and Gynaecological Sciences, University of Messina, Building A, c/o AOU Policlinico G. Martino, Via C. Valeria, Gazzi, 98125, Italy
- AB and RG equally contributed to this paper.
Onofrio Triolo
- Department of Obstetrical and Gynaecological Sciences, University of Messina, Building A, c/o AOU Policlinico G. Martino, Via C. Valeria, Gazzi, 98125, Italy
Daniela Villari
- Department of Human Pathology, University of Messina, Building D, c/o AOU Policlinico G. Martino, Via C. Valeria, Gazzi, 98125, Messina, Italy
Daniele Maisano
- Department of Human Pathology, University of Messina, Building D, c/o AOU Policlinico G. Martino, Via C. Valeria, Gazzi, 98125, Messina, Italy
Domenico Giordano
- Department of Obstetrical and Gynaecological Sciences, University of Messina, Building A, c/o AOU Policlinico G. Martino, Via C. Valeria, Gazzi, 98125, Italy
Domenica Altavilla
- Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria, Gazzi, 98125, Messina, Italy
Herbert Marini
- Department of Biochemical, Physiological and Nutritional Sciences, Section of Physiology and Human Nutrition, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria, Gazzi, 98125, Messina, Italy
Elena Bianca Adamo
- Department of Biochemical, Physiological and Nutritional Sciences, Section of Physiology and Human Nutrition, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria, Gazzi, 98125, Messina, Italy
Piero Antonio Nicotina
- Department of Human Pathology, University of Messina, Building D, c/o AOU Policlinico G. Martino, Via C. Valeria, Gazzi, 98125, Messina, Italy
Rosario D’Anna
- Department of Obstetrical and Gynaecological Sciences, University of Messina, Building A, c/o AOU Policlinico G. Martino, Via C. Valeria, Gazzi, 98125, Italy
Francesco Squadrito
- Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria, Gazzi, 98125, Messina, Italy
- Corresponding author. Tel.: +39 090 2213648; fax: +39 090 2213300.

published online 31 May 2010.

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; 54mg/day); norethisterone acetate (n=19; 10mg/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.

Abbreviations: ER, estrogen receptor, PR, progesterone receptor, FSH, follicle stimulating hormone, LH, luteinizing hormone, E2, estradiol, SHBG, sex hormone-binding globulin, PG, progesterone, BRCA, breast cancer associate gene, PPAR, peroxisome proliferator activated receptor