IS LETROZOLE AFFECTING THE BENEFICIAL CHANGES OF DESOGESTREL AT THE ENDOMETRIAL LEVEL IN PATIENTS WITH ENDOMETRIOSIS?

MERESMAN GABRIELA; OLIVARES CARLA; STELLA INES; ELENA HERNÁN; SUELDO CARLOS

San Francisco, California

Congreso; 64th Annual Meeting of the American Society of Reproductive Medicine; 2008

American Society of Reproductive Medicine

IS LETROZOLE AFFECTING THE BENEFICIAL CHANGES OF DESOGESTREL AT THE ENDOMETRIAL LEVEL IN PATIENTS WITH ENDOMETRIOSIS? Objective: Cell proliferation is increased and apoptosis is diminished in eutopic endometrium from patients with endometriosis (EDT), factors that may contribute to its etiopathogenesis. We previously described the reversal of those findings with the use of desogestrel (Meresman et al, 2005). In patients with EDT treated with aromatase inhibitors, a progestin is also administered in order to block the release of gonadotropins (Ailawadi et al, 2004). In the present study, we evaluated and compared the endometrial effects of treatment with desogestrel and a combination of letrozole and desogestrel on these parameters in patients with histologically proven EDT. Design: Apoptosis and cell proliferation were evaluated in eutopic endometrial tissue from EDT patients Material and methods: 10 EDT patients had an endometrial biopsy before treatment, after 6 weeks of desogestrel 75 µg/day (treatment D) and then, after another 6 weeks of a combination of desogestrel 75 µg + letrozole 2.5 mg/day (treatment DL). The lesions were then fixed and stained with hematoxylin-eosin for histological analysis. Cell proliferation was assessed by PCNA immunohistochemistry before and after treatments. Determination of apoptosis was done in the same tissue by the TUNEL assay. Results: PCNA index was assessed in eutopic endometrium from EDT patients before treatment and observed 36.08±4.8% positive cells. After treatment D, cell proliferation was significantly suppressed to 12.36±2.8% positive cells (p<0.01). Similarly, the treatment DL caused a significant decrease in cell proliferation to 14.71±3.9% positive cells (p<0.01). Likewise, both treatments significantly increased apoptosis in eutopic endometrium from EDT patients from 2.49±0.6% apoptotic cells (APc) before treatment to 12.98±2.1% APc after desogestrel administration (p<0.01) and to 12.2±3.7% APc after the combined treatment (p<0.01). Histologically, under treatment D the endometrial glands and the stroma showed discrepancy, with a more advanced stroma, highlighted by progestational changes and minimal proliferation,  while under treatment DL both endometrial components showed advanced progestational changes and complete absence of endometrial proliferation. Conclusion: Desogestrel and the combination of letrozole and desogestrel significantly diminished cell proliferation and induced apoptosis in eutopic endometrial tissue from EDT patients. These data may have clinical relevance in the treatment of EDT. Support: This study was supported by the National Research Council of Argentina (CONICET), Argentina.