Changes in tissue inflammation, angiogenesis and apoptosis in endometriosis, adenomyosis and uterine myoma after GnRH agonist therapy

Background: Information is limited regarding multifunctional role of GnRH agonist (GnRHa) therapy in reproductive diseases. We investigated pattern of changes in inflammatory reaction, micro-vessel density and apoptosis in the tissues collected from women with endometriosis, adenomyosis and uterine myoma who were treated with or without GnRHa therapy. Methods: Biopsy specimens were collected from lesions, myometria and corresponding endometria of 45 women with ovarian endometrioma, 35 women with adenomyosis, and 56 women with uterine myoma. A fraction of these women were treated with GnRHa therapy for a variable period of 3-6 months before surgery. We performed immunohistochemical analysis of CD68, a macrophage (Mφ) marker, and von Willebrand factor (VWF), a vessel marker, using respective antibodies. The changes in apoptosis were examined using TdT-mediated dUTP-biotin nick end-labeling (TUNEL) assay and by the immunoexpression of activated caspase-3 in tissues after GnRHa therapy. Results: The infiltration of CD68-positive M φ and VWF-positive micro-vessel density were significantly decreased in the endometria of women with endometriosis, adenomyosis and uterine myoma in the GnRHa-treated group when compared with that in the non-treated group. A marked decrease in inflammatory and angiogenic responses were observed in lesions and myometria of these diseases. When compared with non-treated group, a significantly increase in apoptotic index (apoptotic cells per 10 mm2 area) and quantitative-histogram (Q-H) scores of activated caspase-3 after GnRHa therapy were observed in the eutopic endometria, lesions and myometria of these diseases. Conclusion: GnRH agonist was able to markedly reduce the inflammatory reaction and angiogenesis and significantly induce apoptosis in tissues derived from women with endometriosis, adenomyosis and uterine myoma. These multiple biological effects at the tissue level may be involved in the regression of these reproductive diseases