Effects of hormonal treatment on the expression of collagen type I, matrix metalloproteinase-1, and tissue inhibitor of metalloproteinases-1 in endometriosis

OBJECTIVES: Endometriosis is an estrogen-dependent disease, and hormonal treatment is the most common treatment. Both deep infiltrating endometriosis (DIE) and ovarian endometrioma (OV) are characterized by dense surrounding fibrotic tissue. However, no studies have examined the effect of hormonal treatment on fibrosis in endometriotic lesions. In the present study, we evaluated the effects of hormonal treatment on collagen type I, matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinases 1 (TIMP-1) protein expression in DIE and OV lesions. STUDY DESIGN: Immunohistochemical analyses in a total of 228 patients were performed on paraffin-embedded endometriosis tissue samples collected prospectively. Among them, a total of 164 patients who underwent laparoscopic surgery for DIE and/or OV received preoperative hormone treatment (continuous combined oral contraceptive [CO], progestin, or gonadotropin-releasing hormone agonist [GnRHa]) for at least three months prior to surgery. For comparison, paired endometrial and endometriotic samples were used from 40 age-matched patients with DIE and/or OV, as well as endometrial samples from a total of 24 women undergoing tubal ligation or reversal. RESULTS: Continuous CO, progestins, and GnRHa decreased collagen type I protein expression in DIE but had no significant effect on OV. Furthermore, TIMP-1 protein expression in DIE was significantly lower than in OV, and hormonal treatment further decreased TIMP-1 expression in DIE but not in OV. The decreased fibrosis observed in DIE may be due, in part, to decreased levels of TIMP-1 resulting from hormonal treatment. CONCLUSIONS: Hormonal treatment reduces fibrosis in DIE. However, it has no significant effect on OV.