Hormonal treatment in endometriosis fails to prevent IL-6 increase and endometrium fibrosis but regulates levels of CYP17A, VEGF, and NFkB.

Endometriosis is a gynecological inflammatory disease characterized by the presence of ectopic endometrial-like tissue. This study aims to elucidate the effect of hormonal treatment in human endometriosis inflammation, angiogenesis and fibrosis. Eutopic and ectopic endometrium and blood were harvested from women with hormone-treated endometriosis (n = 24) and from controls (n = 15). Inflammation was assessed by quantification of EGF-like module containing mucin-like hormone receptor (EMR1), galectin-3 and nuclear factor kappa B in tissues, and interleukin-6 and transforming growth factor-beta (TGF-β) in blood. Fibrosis was evaluated in Picrosirius Red-stained sections by computer-assisted analysis and by quantification of metalloproteinase-3 in tissues. Levels of metalloproteinase-3 together with vascular endothelial growth factor (VEGF) elucidated endometriosis-associated angiogenesis and CYP17A and proliferating cell nuclear antigen (PCNA) estrogen synthesis and cell proliferation, respectively. Endometriosis patients exhibited increased fibrosis in ectopic lesions and elevated blood interleukin-6 levels. On the other hand, no differences were found in CYP17A, metalloproteinase-3, VEGF and NFkB between patients with hormone-treated endometriosis and controls. Also, TGF-β in blood presented equivalent levels between patients and controls. PCNA and galectin-3 decreased, while EMR1 increased, in the tissues from patients comparatively with controls. Hormonal treatment restores levels of CYP17A, VEGF and NFkB in endometrium to levels found in healthy women, which demonstrates an amelioration in estrogen secretion, angiogenic pathways and inflammation, dysregulated in endometriosis, though the increase in fibrosis found in the ectopic endometrium, which is a manifestation of the chronic inflammatory demand, is not circumvented by the hormonal therapy.