Rapid Reduction of Leiomyoma Volume During Treatment With the GnRH Antagonist Ganirelix

Abstract

Twenty premenopausal women with symptomatic fibroids, who were scheduled for surgery, participated in a prospective, open-label study evaluating the rapidity and maximum reduction of leiomyomata volume possible using daily treatments with 2 mg of the GnRH antagonist ganirelix. Before starting and after completing treatment, and at weekly intervals during treatment, the size and location of leiomyomas were evaluated using an ultrasound scan (USS), and blood samples were taken for a serum hormone analysis. In addition, magnetic resonance imaging (MRI) was performed before treatment and after maximum reduction. Maximum reduction was considered to have occurred when four consecutive USS measurements found less than a 10% decrease. Treatment consisted of daily subcutaneous injections of 2 mg ganirelix given in the upper leg by the study subjects themselves. Treatment continued until maximum reduction in leiomyomata and uterine volume was achieved, but for no more than 12 weeks. Nineteen women completed the treatment regimen. Initial USS assessment found leiomyoma volumes ranging from 2.9 to 1085.2 mL, and baseline MRI measurements ranged from 3.6 to 1015.5 mL. Corresponding uterine volume measurements were 50.3 to 1085.2 mL with USS and 64.3 to 1612.7 mL with MRI. There were 7 submucosal, 10 intramural, 1 transmural, and 9 subserosal leiomyomas identified in the 19 women. Six were located on the anterior wall, 12 on the posterior wall, and 9 in the fundus. USS assessments found a median decrease of -42.7% (range, -77.0% to 14.1%) in leiomyoma volume and a decrease of -46.6% (range, -78.6% to -6.1%) in uterine volume. Baseline and end point MRI measurements showed a median decrease in leiomyoma volume of -29.2% (range, -62.2% to 35.6%) and a median decrease in uterine volume of -25.2% (range, -63.6% to 28.9%). The median length of treatment was 19 days (range, 1-65 days) to achieve maximum leiomyoma reduction and 17 days (range, 8-52 days) for maximum reduction in uterine size. In the serum hormone analyses, serum LH and E 2 were undetectable at the first weekly assessment and remained too low to measure throughout the trial. Median FSH values dropped to below 2 IU/L by the third weekly assessment and stayed there. Progesterone concentrations were low throughout the study. Reported side effects included hot flushes, which were experienced by 75% of patients, and headaches, which occurred in 45% of study subjects. Eight women reported symptoms in the first week but most appeared in the third week. Only two of the 19 women had no adverse events.