Effects of the levonorgestrel-releasing intrauterine system on cell proliferation, Fas expression and steroid receptors in endometriosis lesions and normal endometrium.
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 alpha (ER-alpha) 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-alpha 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-alpha and increased Fas expression in the eutopic and ectopic endometrium of patients with endometriosis. Some of these actions were not observed with GnRHa.
Gomes
M K O
MK
Department of Obstetrics and Gynecology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.
Rosa-e-Silva
J C
JC
Garcia
S B
SB
de Sá Rosa-e-Silva
A C Japur
AC
Turatti
A
A
Vieira
C S
CS
Ferriani
R A
RA
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004715:Endometriosis / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000209:etiology; D011980:Receptors, Progesterone / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
D047628:Estrogen Receptor alpha; C491901:FAS protein, human; D011980:Receptors, Progesterone; D019014:fas Receptor; D007987:Gonadotropin-Releasing Hormone; D016912:Levonorgestrel