The efficacy and safety of the gonadotropin-releasing hormone agonist nafarelin for treatment of endometriosis were compared with those of danazol in two large-scale, double-blind trials. Assessments of severity of symptoms, laparoscopic scores before and after therapy, and pregnancy rates showed that nafarelin, 400 and 800 micrograms administered intranasally, was as efficacious as oral danazol, 600 and 800 mg. The adverse effects seen with nafarelin, mainly hot flashes, were related to its mode of action, namely hypoestrogenemia induced by reversible inhibition of ovarian hormone production. Hypoestrogenemia was associated with a decrease of bone density in the lumbar vertebrae, but these changes were partially or completely reversible after treatment was discontinued. No significant changes in bone mass occurred in the distal radius. Danazol was associated with androgenic and metabolic adverse effects, including weight gain, negative effects on the lipid profile, and elevated liver enzyme levels. Nafarelin was found to be as effective as danazol for the management of endometriosis, with a different and more favorable safety profile.