Effect of metformi̇n and dienogest on PI3K/AKT expression in rats with endometriosis

Endometriosis is widely available, benign, and accessible, presenting with pelvic pain and infertility. The aim of our study is to explain the improvement ratio of Dienogest and Metformin treatments given to endometriosis and their coding on the PI3K/AKT signal pathway. In our study, rats were randomly divided into groups. Control: (n=8) Group to which nothing was applied; Endometriosis (n=8): Experimental endometriosis procedures group; Endometriosis+Dienogest: (n=8) Experimental endometriosis applications and the group given Dienogest 0.3 mg/kg/day orally for 28 days; Endometriosis+Metformin: (n=8) Experimental endometriosis treatment and Metformin 100 mg/kg/day orally administered group. All doses are learned orally from day 21 to day 49. On the 49th day, the endometrial lesion area was re-evaluated, the left uterine horn was removed and the animals were sacrificed. Estradiol, progesterone and VEGF analysis from blood samples were analyzed by ELISA method. After detecting formaldehyde in the tissues taken, sections were taken and stained with hematoxylin and eosin following routine tissue follow-up. PI3K, p-PI3K, AKT, p-AKT reactions in tissues were evaluated immunohistochemically. PI3K, p-PI3K, and AKT mRNA expression changes in rat endometriosis and uterine tissues were measured using reverse transcription-polymerase chain methods (RT-PCR). No significant differences were detected between the initial and final weights of the groups. Blood E2 levels were found to be significantly higher in the Endometriosis + Metformin groups compared to the other groups. Progesterone and E2 levels were higher in the Dienogest groups than in the control group. It was not statistically significant. The highest values were in the Endometriosis + Metformin group. Lesion diameter decreased in both Dienogest and Metformin groups. The decrease in Metformin groups was significant (P<0.05). PI3K, p-PI3K and AKT expression was increased in the treatment groups in the endometriosis focus. However, PI3K and p-PI3K expression was found to decrease in uterine tissue. AKT expression was statistically significantly higher in the metformin group. In conclusion, Metformin and Dienogest caused regression of endometriosis implants in the endometriosis rat model. Metformin treatment was found to be the most effective treatment at the macroscopic, biochemical, microscopic and molecular levels.