Hum. Reprod. Advance Access originally published online on August 6, 2009
Human Reproduction 2009 24(11):2736-2745; doi:10.1093/humrep/dep288
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Effects of the levonorgestrel-releasing intrauterine system on cell proliferation, Fas expression and steroid receptors in endometriosis lesions and normal endometrium
1 Department of Obstetrics and Gynecology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil 2 Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo 14049-900, Ribeirão Preto, SP, Brazil
3 Correspondence address. Departamento de Ginecologia e Obstetrícia, Faculdade de Medicina de Ribeirão Preto, USP, Av. Bandeirantes, n°3900-8° andar, 14049-900 Ribeirão Preto, SP, Brazil. Tel: +55 1636022231; Fax: +55 1636339633; E-mail: raferria{at}fmrp.usp.br
BACKGROUND: The objectives of this study were: (i) to evaluate the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) on both proliferation and apoptosis markers and hormone receptors of the eutopic and ectopic endometrium of women experiencing pain related to endometriosis and (ii) to compare the results with those obtained with GnRH agonist (GnRHa) injections.
METHODS: Pre- and post-treatment endometrium and endometriosis specimens were obtained from 22 women experiencing pain related to endometriosis who were treated with LNG-IUS (n = 11) or GnRHa (n = 11) for 6 months. Changes in the expression of proliferating cell nuclear antigen, Fas, progesterone receptor (PRA) and estrogen receptor 
(ER-) were analyzed by immunohistochemistry.
RESULTS: The cell proliferation index was significantly reduced in the epithelium and stroma of both the eutopic and the ectopic endometrium after treatment with the LNG-IUS and GnRHa. Only LNG-IUS users showed an increased H-score for Fas in the epithelium of the eutopic and ectopic endometrium (P < 0.05). Expression of ER- and PRA by the glandular epithelium was lower in the eutopic endometrium after both treatments, but this reduction was noted in the ectopic endometrium only after LNG-IUS treatments (P < 0.05). No difference was detected between groups for any of the markers.
CONCLUSIONS: LNG-IUS reduced both cell proliferation and the expression of PRA and ER- and increased Fas expression in the eutopic and ectopic endometrium of patients with endometriosis. Some of these actions were not observed with GnRHa.
Key words: endometriosis/levonorgestrel-releasing intrauterine system/GnRH agonist/apoptosis/steroid receptor
Submitted on March 28, 2009; resubmitted on July 2, 2009; accepted on July 10, 2009.