Beneficial effects of aromatase inhibitors on endometriotic lesions in an animal model.

BILOTAS M.; MERESMAN G.; STELLA I.; SUELDO C.E.; BARAÑAO R.I.

Woods Hole, Massachusetts, USA

Simposio; Frontiers in Reproduction 11th Annual Symposium; 2008

Marine Biological Laboratories. Woods Hole, Massachusetts, USA

OBJECTIVE: To evaluate the effect of aromatase inhibitors, letrozole and anastrozole, on the implantation, cell proliferation and apoptosis of ectopic endometrium, and on the release of pro-angiogenic and pro-inflammatory factors in peritoneal fluid. Methods: Balb/c mice had surgery performed to induce endometriotic-like lesions. Treatment with anastrozole, letrozole or saline (control) was started on either postoperative day 1 or 28.  After four weeks, animals were sacrificed, peritoneal fluid was collected and endometriotic lesions were counted and measured. Cell proliferation was assessed by PCNA immunohistochemistry and apoptosis was evaluated by TUNEL. VEGF and PGE levels were assayed by ELISA and RIA respectively. Results: Treatment with anastrozole and letrozole did not prevent lesion establishment, however it significantly decreased endometriotic lesions size (p<0.05). Also, letrozole and anastrozole decreased cell proliferation (p<0.01) and anastrozole increased apoptosis in both treatment designs (p<0.05). Letrozole augmented apoptosis only when treatment was initiated on postoperative day 1 (p<0.01). In addition, letrozole reduced VEGF and PGE levels in peritoneal fluid (p<0.05 and p<0.001). However anastrozole diminished VEGF levels (p<0.05) and did not change PGE content. Conclusions: aromatase inhibitors diminish endometriotic lesion size by decreasing cell proliferation and increasing apoptosis. Furthermore, they decrease pro-angiogenic and pro-inflammatory factors in peritoneal fluid.