Gonadotropin-releasing hormone agonist induces apoptosis and reduces cell proliferation in eutopic endometrial cultures from women with endometriosis

Objective: There is growing evidence that suggests a direct action of gonadotropin-releasing hormone agonist (GnRH-a) on endometrial growth. Consequently, our purpose was to evaluate the effect of GnRH-a on in vitro eutopic endometrial cell growth and apoptosis. Design: Prospective study. Setting: Research institute and clinical fertility center. Patient(s): Sixteen women with untreated endometriosis and 14 controls. Intervention(s): Biopsy specimens of eutopic endometrium were obtained from all subjects. Apoptosis and cell proliferation were examined in epithelial endometrial cell cultures after incubation with leuprolide acetate (LA), antide, and a combination of both. Main Outcome Measure(s): The percentage of apoptotic cells was evaluated by the acridine orange-ethidium bromide technique; cell proliferation was assessed In by H-3-thymidine incorporation. Result(s): Leuprolide acetate (LA) (100 ng/mL) enhanced apoptosis in endometrial cultures from patients with endometriosis and controls, and this effect was reversed by antide 10(-7)M. Cell proliferation was down-regulated by LA at 1, 10, and 100 ng/mL in cultures from women without and with endometriosis. The addition of antide 10(-7) M reversed this inhibition. Conclusion(s): GnRH-a appears to have a direct effect by enhancing the apoptotic index and decreasing the cell proliferation in endometrial cells. (C) 2003 by American Society for Reproductive Medicine.