RAPID REGRESSION OF UTERINE LEIOMYOMAS IN RESPONSE TO DAILY ADMINISTRATION OF GONADOTROPIN-RELEASING-HORMONE ANTAGONIST

Objective: The efficacy of acute and sustained pituitary gonadotropin down-regulation by the Nal-Glu GnRH antagonist (Nal-Glu) was evaluated in the treatment of uterine leiomyomas. Design: Prospective, open cli nical trial. Patients: Seven normally cycling women with symptomatic l eiomyomas. Interventions: Nal-Glu (50 mug/kg per day) was administered subcutaneously for 3 months. Main Outcome Measures: Baseline ultrasou nd examinations were obtained and repeated monthly throughout treatmen t. Each leiomyoma was mapped and measured in three dimensions. Blood s amples were drawn daily for 7 days, weekly for 4 weeks, and monthly fo r the remaining 2 months. Results: Mean leiomyoma size decreased 52.8 +/- 7.3% (means +/- SD) after 1 month of therapy and remained unchange d for the remainder of the study. Serum levels of E2 (35.9 +/- 11.8 to 9.3 +/- 0.8 pg/mL, 131.7 +/- 43.3 to 34.0 +/- 1.4 pmol/L), estrone (3 7.3 +/- 7.5 to 13.0 +/- 2.5 pg/mL, 138.1 +/- 27.7 to 48.1 +/- 9.1 pmol /L), and P (1.6 +/- 1.1 to 0.3 +/- 0.01 ng/mL, 5.0 +/- 3.6 to 0.9 +/- 0.04 nmol/L) declined rapidly (within 48 hours) and remained suppresse d throughout treatment. Serum LH, FSH, androstenedione, T, and DHEA le vels did not change significantly. In two subjects who did not have su rgical removal, leiomyomas grew to original size within the lst month off drug. Six patients remained amenorrheic and the other subject spot ted during the last 2 months of therapy. Conclusions: Continuous treat ment with Nal-Glu induces immediate and sustained pituitary-gonadal do wn-regulation that results in regression in leiomyoma size. By circumv enting GnRH agonist-induced pituitary-ovarian up-regulation, GnRH anta gonists may prove to be superior tools in the medical management of le iomyomas.