Effects of Ethinyl Estradiol in Combined Oral Contraceptives on Cell Proliferation and Apoptosis in Ectopic Endometrial Tissue: A Randomized Controlled Study

Abstract

Objective: Since endometriosis is an estrogen-dependent disease; therefore, combined oral contraceptives (COCs) may not be the best choice for the treatment of endometriosis. The objective of the present study was to investigate the effects of ethinyl estradiol (EE) and desogestrel (DSG) in COCs on cell proliferation and apoptosis in ectopic endometrial tissue as compared to DSG alone.
 Materials and methods: Forty-five women of reproductive age with at least one endometriotic cyst were recruited into this single-blind randomized controlled trial study and randomly divided equally into three groups. EE-DSG and DSG groups received EE (0.03 mg) and DSG (0.15 mg) or DSG alone daily for 28-35 days before surgery. The control group was prescribed nothing. Endometriotic cyst tissues were collected during ovarian cystectomy for immunohistochemistry.
 Results: Levels of Ki-67 positive cells in the ectopic endometrial tissue of the EE-DSG group were significantly higher than the DSG group (median [IQR]; 1.4[1.2] vs 0.6 [0.7], P <0.016). There were significantly more TUNEL-positive cells in the EE-DSG group compared to the DSG group (median [IQR]; 2.8[0.7] vs 1.8[1.4], P < 0.016, respectively). Moreover, the number of TUNEL-positive cells in the EE-DSG and DSG groups were significantly higher than the control (median [IQR]; 2.8[0.7] vs 0.2[0.2] and 1.8[1.4] vs 0.2[0.2], P <0.016). The levels of cells that positively stained for Bcl2 were not different among all groups.
 Conclusion: Progestin alone increased cell apoptosis in ectopic endometria. However, concurrent EE in COCs enhanced proliferation and promoted a greater apoptotic effect in ectopic endometria compared to progestin alone.

Review of the Potential Therapeutic Effects and Molecular Mechanisms of Resveratrol on Endometriosis

“… 42 Previous studies have shown an incremental cell proliferation rate of ectopic endometrium in endometriotic patients, which is conductive to survival and implantation into the ectopic site. 50 Proliferating cell nuclear antigen (PCNA), a sensitive indicator of proliferation and DNA restoration, exists in the G1, S and G2 phases of the cell cycle, while Ki-67 exists in all active phases and is a more specific proliferative marker than PCNA. 51 The proliferative ability of cells is usually be assessed by detecting the expression of proliferative markers.…”