The aim of this study was to evaluate the effect of long-term use of progesterone treatment on proliferation and apoptosis in simple endometrial hyperplasia without atypia. In this prospective control study, endometrial tissue samples of 19 patients with simple endometrial hyperplasia without atypia (group 1), posttreatment biopsy materials of the patients after 3 months of cyclic progesterone treatment with noretisterone for 10 days (group 2), and 18 endometrial biopsy materials of the control group (group 3) were examined for proliferative and apoptotic activities. There was a statistically significant difference between the median values of the proliferative index of the three groups (P = 0.000). The proliferative index was significantly higher in the endometrial hyperplasia group than in posttreatment group (P = 0.000). But there was no significant difference between posttreatment group and control group. The median value of apoptotic activity was significantly different between three groups (P = 0.000). Apoptotic index was highest in hyperplasia group. A significant decrease in apoptosis was observed after the progesterone treatment (P = 0.002). The lowest apoptotic activity was detected in the control group. In conclusion, 3 months of cyclic progesterone treatment reduces both proliferative and apoptotic activities in endometrial tissue with simple hyperplasia.