Gonadotropin-releasing hormone agonist therapy reduces postoperative adhesion formation and reformation after adhesiolysis in rat models for adhesion formation and endometriosis

OBJECTIVES: To evaluate the effectiveness of GnRH agonist (GnRH-a) therapy on adhesion formation and reformation in established rat models for surgically induced adhesion formation and endometriosis. DESIGN: Before surgery, female Sprague-Dawley rats were injected with GnRH-a or control diluent. Six days later, rats were assigned to one of four surgical groups: [1] endometriosis, [2] endometriosis sham, [3] adhesion model, or [4] adhesion sham. Three weeks after surgery, a second-look laparotomy was performed, adhesions were scored (0 = no adhesions to 3 = severe adhesions) and mechanically disrupted, and rats received a second GnRH-a or diluent injection either analogous to their initial injection or in a crossover design. Three weeks after the second injection, rats were killed and adhesion reformation was scored. Data were evaluated using nonparameteric tests including Mann-Whitney, Kruskal-Wallis, and Friedman's tests comparing GnRH-a treatments with diluent controls. RESULTS: Preoperative GnRH-a therapy reduced adhesion scores in rats with surgically induced endometriosis (mean +/- SEM; GnRH-a 1.1 +/- 0.2 versus diluent 2.2 +/- 0.2) and adhesions (GnRH-a 0.3 +/- 0.1 versus diluent 0.6 +/- 0.1). Pretreatment GnRH-a therapy did not affect adhesion scores in the endometriosis sham procedure. Combined preoperative and postoperative GnRHa therapy (GnRH-a-GnRH-a) but not postoperative GnRH-a therapy alone (diluent-GnRH-a) reduced adhesion reformation after adhesiolysis in the endometriosis model (GnRH-a-GnRH-a 1.1 +/- 0.3, diluent-GnRH-a 1.6 +/- 0.7), the endometriosis sham (GnRH-a-GnRH-a 0.7 +/- 0.2, diluent-GnRHa 1.8 +/- 0.1), and the adhesion model (GnRH-a-GnRH-a 0.3 +/- 0.2, diluent-GnRHa 1.0 +/- 0.5). No adhesions were observed in the adhesion sham group. CONCLUSIONS: Gonadotropin-releasing hormone agonist therapy was successful in reducing adhesion formation and reformation. These studies suggest that GnRH-a therapy for adhesion prevention in women should be explored.