Genistein reduces angiogenesis and apoptosis in women with endometrial hyperplasia

Abstract

Endometrial hyperplasia without cytological atypia is commonly treated with progestins, 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 , 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.

Natural Kinase Inhibitors for the Treatment and Management of Endometrial/Uterine Cancer: Preclinical to Clinical Studies

“…Genistein ( Figure 3 ) is a naturally occurring isoflavone derivative that binds to the endoplasmic reticulum (ER) as an agonist or antagonist, acting as a selective ER modulator having full agonistic activity on the α-receptor and partial agonistic activity on the β-receptor, demonstrating a modulatory action of genistein on cell apoptosis and growth-related pathways in the hyperplastic endometrium. In the presence of a hyperestrogenic environment in premenopausal women with endometrial hyperplasia, genistein exhibited a substantial reduction in the endometrial hyperplasia and associated symptoms ( Bitto et al, 2015 ).…”

Genistein: Dual Role in Women’s Health

“…Given genistein’s ability to mimic estrogen and endometriosis’ hormone-responsiveness [ 160 ], a reasonable hypothesis might assert that genistein could affect the incidence, severity, or timing of endometriosis that affects thousands of premenopausal women in the United States. Though 54 mg of oral genistein consumed daily has been shown to be an effective alternative treatment for managing endometrial hyperplasia in premenopausal women [ 161 ], much of the literature regarding its effects on endometriosis in women is conflicting. A large majority of it appears to be focused on in vivo rodent studies.…”