A combination therapy of danazol and GnRH agonist for endometriosis

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Autocrine growth mechanism of endometriosis and inhibitory effects of danazol and GnRH agonist on the growth of endometriosis were investigated Danazol treatment did not show suppressive effects on hypothalamic-pituitary-pvarian axis in patients whih endometriosis. Danazol also did not inhibit estrogen production by the ovary through its direct action on the ovary. It is suggested that the inhibitory effect of danazol on the growth of endometriosis is mediated through progestin and androgen receptors in the cells. In contrast, the mechanism of action of GnRH agonist-induced resorption of endometriosis is estrogen deprivation and subsequent atrophy. GnRH agonist administration resulted in a significant suppression of the serum level of bioactive LH, of the pulsatility of LH release, and of the pituitary response to GnRH (Endocrinol Japon 39 : 615, 1992, In Vivo 7 : 127, 1993, Fertil Steril, in press).Human endometrial adenocarcinoma cells produce angiogenic factors such as TGF-beta and … More FGF.Progestin MPA inhibited neovascularization induced by the angiogenic factors that were secreted by adenocarcinoma cells. It is possible that progestins suppress the angiogenesis in endometriosis and inhibit the progressive growth of the disease (Am J Obstet Gynecol 167 : 207, 1992, Int J Cancer 54 : 862, 1993).Effects of Danazol, GnRH agonist, and a combination of danazol and GnRH agonist on endometriosis were evaluated in randomly assigned 66 patients. Pretreatment and post-treatment laparoscopies were compared by means of the American Fertility Society's scoring system. The mean laparoscopic scores significantly decreased with either danazol or GnRH agonist buserelin. However, the beneficial effects of the treatments in patients with Stage III or disease were not prominent. There was no statistically significant improvement with the combination therapy because the group consisted of patients with high score. It is concluded that the potential application of a combination therapy of danazol and Gnrh agonist, which shows different modes of action, in treatment of patients with advanced endometriosis should be evaluated with large scale clinical trials (Am J Obstet Gynecol 167 : 271, 1992, Fertil, in press). Less