Desogestrel suppresses cell proliferaton and enhances apoptosis of eutopic endometrial issue from patients with endometriosis.

MERESMAN G; ABELLLO V; BARAÑAO RI; AUGÉ L; TESONE M; SUELDO C

Montreal, Canada

Congreso; Conjoint Annual Meeting of the ASRM & CFAS; 2005

American Society of Reproductive Medicine

Desogestrel suppresses cell proliferation and enhances apoptosis of eutopic endometrial tissue from patients with endometriosis. Gabriela F. Meresman, Verónica Abello, Rosa I. Barañao, Luis Augé, Marta Tesone, Carlos Sueldo .   Objective: We demonstrated recently that combination oral contraceptives significantly diminished cell proliferation and induced apoptosis in eutopic endometrial tissue from endometriosis patients (Meresman et al. Fert Steril 77:1141-7, 2002). The use of progestin-only compounds is an effective therapy in the treatment of painful symptoms associated with endometriosis, and showed a good cost-effectiveness balance. Also, Amezcua et al recently demonstrated that apoptosis is an early event in progestin therapy for endometrial hyperplasia (Gynecol Oncol 2000; 79:169-76). However there is limited data evaluating the effect of desogestrel treatment on endometrial growth in endometriosis. Therefore, the purpose of this study was to assess the effect of desogestrel (Cerazette, Organon, Argentina) on cell proliferation and apoptosis in eutopic endometrial tissue from patients with endometriosis. Design: Apoptosis and cell proliferation were evaluated in vitro in eutopic endometrial tissue from endometriosis patients Materials and Methods: 12 endometriosis patients had an endometrial biopsy before and after 30 days of oral desogestrel treatment at 75 mg/day (Cerazette).The assessment of cell proliferation was done by studying the nuclear protein Ki-67 by using immunohistochemical techniques before and after desogestrel treatment. Tissue sections were incubated with anti-human Ki-67 rabbit monoclonal antibody (Dako, USA) following incubation with anti-rabbit-peroxidase conjugate (Dako,USA). Binding was visualized by incubating sections with DAB, and lightly counterstaining with hematoxylin. Immunoreactivity for Ki-67 is only expressed in dividing cells. For apoptosis quantification, the same tissue sections were processed for in situ immunocytochemical localization of nuclei exhibiting DNA fragmentation, by the technique of terminal deoxynucleotidyl transferase-mediated dUTP digoxygenin nick-end labeling (TUNEL), using an apoptosis detection kit (Chemicon, USA). Proliferation and apoptosis were measured as the number of positive cells/field at 1000x magnification. Comparisons among groups were performed by Kruskal-Wallis nonparametric ANOVA test, and Dunn´s multiple comparison test. Results: Before desogestrel, endometriosis patients showed a significant increase in cell proliferation at the epithelial fraction in comparison to after treatment: 2.66 (before desogestrel) vs. 0.73 (after desogestrel) expressed as positive cells/field (p=0.03). There was also a significant decrease observed in apoptosis of epithelial endometrial cells, 0.37 (before desogestrel) and 1.16 (after desogestrel) (p=0.01) expressed as apoptotic cells/field.  Conclusions: Our results showed that a progestin-only treatment with desogestrel significantly diminished cell proliferation and induced apoptosis in eutopic endometrium from endometriosis patients. This data may have clinical relevance in the prevention and recurrence of endometriosis.