Prospective randomized study comparing the GnRH-agonist leuprorelin acetate and the gestagen lynestrenol in the treatment of severe endometriosis

Abstract

Endometriosis is thought to be an ovarian-dependent benign disease that affects up to 12% of women during their reproductive life. For the past ten years the gonadotropin-releasing hormone (GnRH)-agonistshave been proved effective and safe drugs in the treatment of endometriosis.Nevertheless ,gestagens such as lynestrenol still remain the most often used hormonal drugs for the treatment of this disease.The primary objective of this study was to compare the efficacy of the GnRH-agonist leuprorelin acetate depot (LAD) (Enantone®-Gyn) 3.75 mg subcutaneously per month with that of the gestagenlynestrenol (LYN) (Orgametril®) 5 mg orally twice per day in women with severe endometriosis ,in terms of postoperative revised American Fertility Society (r-AFS) scores I-IV at first-looklaparoscopy (score after removal of endometriotic lesions or adhesions) to the r-AFS score after six months' treatment. Secondary objectives were the improvement of clinical symptoms and the side-effectprofile.Forty-eight women with postoperative r-AFS scores I-IV were evaluated in an open prospective randomized study between 1996 and 1998. All the participants underwent a first-look laparoscopywith resection of endometriotic lesions and six months' therapy with one of the above mentioned drugs ,and a further second-look laparoscopy.The six months' treatment with LAD or LYN led to a significantreduction of the r-AFS score points in both groups. The mean r-AFS score in points for the LAD group after the first-look laparoscopy was 21.8 and was 27.2 for the LYN group. After the medical treatmenta mean value of 11.5 points was observed in the LAD group compared with a mean value of 25.5 in the LYN group. This difference was statistically significant (p = 0.000014 ,Wilcoxon test). The improvementin the symptoms of dysmenorrhea ,chronic pelvic pain and dyspareunia was also more pronounced in the LAD-treated group. LAD was more effective than LYN in the suppression of circulating serum 17β-estradiollevels after 6 months of treatment (mean 27.7 ± 9.3 pg/ml versus 42.6 ± 59.3 pg/ml). All the observed side-effects were deemed tolerable by the women who participated in this study. As thereduction of the r-AFS score in points was much more pronounced in the LAD group than in the LYN group ,GnRH-agonists should therefore be used as first-choice drugs in the treatment of endometriosis. Dueto the limited treatment of 6 months' duration of GnRHagonists ,gestagens might be used as second-line drugs for long-term and continuous treatment in the management of endometriosis to maintain the primarybeneficial effect of GnRH-agonist treatment in patients who have completed their families.