Effects of Raloxifene and GnRH-a on VEGF expression in cultured human uterine leiomyoma cells

Background: uterine leiomyoma is the most common benign pelvic tumor in women of reproductive age and is frequently associated with abnormal uterine bleeding and pelvic pressure. Combined therapy of gonadotropin-releasing hormone analogue (GnRH-a) and selective estrogen receptor inhibitors (raloxifene) reduce the  size of leiomyoma.

Methods: Twelve uterine leiomyomas were obtained from pre-menopausal women with regular menstrual cycles in the proliferative phase who underwent abdominal hysterectomy or myomectomy in Imam Reza Hospital. The patients had received no hormonal therapy for at least 6 months before surgery.The comparative effects of treatment with graded concentrations of raloxifene (in five groups with various concentrations of 1, 2, 4, 6 and 8 micrograms per milliliter, respectively) and GnRH-a (in five groups, with concentrations of 50, 100, 200, 300 and 400 micrograms per milliliter, respectively) and combination of these two on Vascular Endothelial Growth Factor (VEGF) and inhibition of leiomyoma cell proliferation were determined.

Results: in the three treatment groups with graded concentration of raloxifene and GnRH-a and combined therapy, VEGF content significantly decreased (P<0.05). The VEGF decreasing levels in the combined therapy, raloxifene and GnRH-a groups were 79.16%, 64.74% and 55.29%, respectively (p<0.05). The inhibition of cell growth was significantly different between the two treatment groups (P<0.05). The inhibition of cell growth in the combined therapy group was 70.77% followed by raloxifene (60.76%) and GnRH-a (15.83%), which indicated a significant difference (P<0.05). 

Conclusion: Treatment with graded concentrations of Raloxifene, GnRH-a and combination of both Raloxifene and GnRH-a significantly decreased the VEGF content and proliferation of leiomyoma cells.