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

Hum Reprod. 2010 Mar;25(3):642-53. doi: 10.1093/humrep/dep437. Epub 2009 Dec 15.

Abstract

Background: Information is limited regarding the multifunctional role of GnRH agonist (GnRHa) therapy in reproductive diseases. We investigated the 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 (Mvarphi) marker and von Willebrand factor (VWF), a vessel marker, using respective antibodies. Changes in apoptosis were examined using TdT-mediated dUTP-biotin nick end-labeling assay and by the immunoexpression of activated caspase-3 in tissues after GnRHa therapy.

Results: The infiltration of CD68-positive Mvarphi 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. Marked decreases in inflammatory and angiogenic responses were observed in lesions and myometria of these diseases. When compared with the non-treated group, a significant increase in apoptotic index (apoptotic cells per 10 mm(2) area) and quantitative-histogram scores of activated caspase-3 after GnRHa therapy were observed in the eutopic endometria, lesions and myometria of these diseases.

Conclusions: GnRHa was able to markedly reduce the inflammatory reaction and angiogenesis and to 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Chemokine CCL2 / metabolism
  • Endometriosis / drug therapy*
  • Endometriosis / pathology
  • Enzyme Activation
  • Female
  • Gonadotropin-Releasing Hormone / agonists*
  • Humans
  • Inflammation / drug therapy*
  • Leiomyoma / drug therapy*
  • Leiomyoma / pathology
  • Leuprolide / therapeutic use*
  • Macrophages / drug effects
  • Macrophages / pathology
  • Uterine Neoplasms / drug therapy*
  • Uterine Neoplasms / pathology
  • von Willebrand Factor / metabolism

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CCL2 protein, human
  • CD68 antigen, human
  • Chemokine CCL2
  • von Willebrand Factor
  • Gonadotropin-Releasing Hormone
  • Caspase 3
  • Leuprolide