Treatment of endometriosis with a potent agonist of gonadotropin-releasing hormone (nafarelin)

Abstract

Administration of superactive agonistic analogs of gonadotropin-releasing hormone (GnRH) has been shown to induce a paradoxic and reversible suppression of gonadotropins, resulting in suppressed gonadal steroid concentrations. Because there currently is no uniformly successful and acceptable medical therapy for endometriosis, we examined the effects of 6 months of nasal administration (500 micrograms every 12 hours) of the agonistic analog of GnRH, nafarelin, on clinical signs and symptoms and hormonal profiles in eight women with endometriosis. All patients had prompt and near-complete relief from their painful symptoms of endometriosis. Laparoscopy or laparotomy, performed both before and after treatment in seven of the women, revealed complete resolution of active endometriotic lesions in five patients and only a single, small cul-de-sac implant in a sixth woman. A large ovarian endometrioma decreased slightly in response to treatment in the seventh woman. Serum luteinizing hormone and follicle-stimulating hormone concentrations, after a transitory stimulation at the onset of treatment, declined and were suppressed (P less than 0.001) during the remainder of treatment. Serum estradiol concentrations fell to approximately menopausal levels (less than 30 pg/ml) after 1 to 4 weeks. Reversibility of drug effect was prompt, with ovulatory menses returning 47 +/- 8 days (+/- standard deviation) after treatment. Thus, nasal administration of agonistic analogs of GnRH may represent a new treatment modality for endometriosis.