The objective of this study was to compare the efficacy of nafarelin 200 micrograms (Group A), nafarelin 400 micrograms (Group B) and the combination of nafarelin 200 micrograms and norethisterone 1.2 mg (Group C) daily, in treating symptoms of endometriosis, American Fertility Society score and adverse events during 6 months of treatment. A prospective, randomized, double-blind parallel group study was performed in two centers and 49 women with endometriosis diagnosed laparoscopically were included. The patients were seen monthly for physical examination and records were taken for bleeding pattern, symptom score and adverse events. A control laparoscopy was performed at the end of 6 months of treatment. All patients were followed 6 months after treatment. At 3 and 6 months the pelvic examination total score had decreased significantly in all three groups. The total endometriosis score was significantly reduced in Groups B and C. After 2 months the total symptom score showed a significant decrease in Groups B and C. The frequency of hot flushes during the first month of treatment was lowest in Group C, but during the rest of treatment there were no differences between the groups. Best bleeding control was obtained in Group C. We conclude that nafarelin 200 micrograms daily has as good an effect on endometriosis symptoms as nafarelin 400 micrograms daily, and the addition of norethisterone 1.2 mg results in fewer hot flushes and better bleeding control.

Twenty-five women with regular menstruation and laparoscopically confirmed endometriosis received 100 mcg nafarelin intranasally twice daily for six months in an open study. American Fertility Society (AFS) laparoscopic scores pre- and post-treatment, symptom severity, hormonal status, bone density and biochemical indices of bone turnover were studied. Five patients were still menstruating at three months and nafarelin was increased to 400 mcg daily. At the end of treatment, the median serum estradiol was 57 pmol/l and all patients were amenorrhoeic. AFS scores for endometriosis improved significantly in 19/23 (82.6%) patients (p = 0.001). Adhesions were not affected. Symptom severity scores were markedly decreased (p < 0.0001) and remained so six months after the end of treatment. Biochemical indices of bone activation were increased but bone loss was insignificant. During treatment, 23/25 patients reported hot flushes. Nafarelin 200 mcg daily significantly reduced signs and symptoms of endometriosis, although five patients needed a dosage increase before menses stopped. The study suggests that lower doses of nafarelin may be efficacious, although symptomatic changes should be treated with caution due to the open and non-comparative nature of the study.