THE EFFECT OF DANAZOL ON PULSATILE GONADOTROPIN-SECRETION IN WOMEN WITH ENDOMETRIOSIS

Objective: To determine whether the effect of danazol on gonadotropin pulsatility was due to a direct effect of the drug or the suppression in the estradiol (E2) levels. Design: Prospective analysis of serial blood samples at 10-minute intervals for 5 hours on days 3, 4, or 5 of the control cycle and 2 months after the start of danazol treatment. Setting: Tertiary institutional outpatient care. Patients, Participants: Six eugonadal women with minimal endometriosis. Interventions: Oral administration of danazol, 200 mg three times daily. Main Outcome Measures: Gonadotropin mean levels, pulse frequency, and amplitude. Results: The mean level of E2 was the same in the control cycle as that during danazol treatment (170 pmol/L). Danazol administration resulted in a 16% increase in the mean luteinizing hormone (LH) pulse amplitude (95% confidence interval [CI] 6% to 26%, P < 0.01), associated with a 20% decrease in LH pulse frequency (95% CI - 71% to + 31%, P = 0.37). There was a nonsignificant increase in follicle-stimulating hormone (FSH) pulse amplitude (2%, 95% CI -9% to + 14%, P = 0.68) and in FSH pulse frequency (27%, 95% CI -4% to + 58%, P = 0.08). The 22% decrease in the mean LH level (95% CI -85% to + 12%, P = 0.13) and the 20% decrease in the mean FSH level (95% CI -53% to +37%, P = 0.33) were also not significant. Conclusions: The increase in LH pulse amplitude represents a direct effect of danazol on the hypothalamic-pituitary axis.