PRELIMINARY RESULTS OF A MULTICENTER TRIAL OF DEPOT LEUPROLIDE ACETATE FOR CENTRAL PRECOCIOUS PUBERTY

Abstract

GnRH analogs are now preferred therapy for central precocious puberty (CPP). Although short term trials of the depot preparation of leuprolide acetate (TAP Pharmaceuticals, Inc.) have been reported, results from large series of patients are unavailable. We report the results of GnRH stimulation tests in 127 patients in screening for CPP at 9 centers over a 20 month period. Fifty-three patients (49 F, mean age 7.0 yr) with peak stimulated LH >10 IU/L (DELFIA) and bone age (BA) advancement >1 yr were enrolled in a protocol initiating 300 ug/kg IM q4wk (7.5-15 mg) before age 9 yr in females and 10 yr in males. Follow-up GnRH stimulation tests were performed at 4, 12, 24, 36, 48, and every 24 weeks thereafter; BA was evaluated q24wk. Comparing baseline and 24wk serum levels (mean±SE), estradiol fell from 19.5±4.9 to <5 pg/ml, peak FSH from 13.3±1.1 to 1.1±0.1 IU/L, and peak LH from 33.1±4.4 to 0.8±0.2 IU/L. Peak LH did not suppress (<1.75 IU/L) in one 13 mo' old female until 36 weeks of therapy. No females had detectable estradiol (>5 pg/ml) during therapy, but 3/4 males had transient delectable testosterone (>10 ng/dl). 86% of subjects showed regression or no change in Tanner breast (or genital) stage. Height velocity diminished from 11.5±0.8 to 6.5±0.7 cm/yr, but BA/CA was unchanged in the first 6 mo. There were no local injection reactions. We conclude that depot leuprolide is immediately effective in suppression of pubertal progression and gonadotropin and sex steroid production, but bone age advancement continues in the initial treatment period. Further data will assess the effect of long term therapy upon predicted and final heights.