Treatment of central precocious puberty, comparison between the leuprorelin 1-month (3.75 mg) and 3-month depot (11.25 mg) formulations

Objective: A new 3-month depot formulation of 11.25 mg leuprorelin, has
been developed recently. The aim of this study was to evaluate the therapeutic
bioequivalence of this new formulation compared with that currently used of
3.75 mg leuprorelin 1-month depot for the treatment of central precocious
puberty (CPP).
Patients and methods: 18 children (17F, 1M) affected by CPP, with onset
of pubertal development before the age of 8 yrs in girls and 9 in boys, were
included in the trial. At the time of the inclusion the patients were under treatment
with montly depot 3.75 mg leuprorelin for 3- 12 months and showed
an adequate gonadotropin suppression (peak LH <3IU/L after GnRH test).
Seven patients were randomly selected for continuing the therapy with 3.75
mg every 4 weeks and 11 children for therapy with 11.25 mg every 12 weeks,
for 1 year period.
Results: In patients treated with the 3-month depot formulation the mean
peak LH and FSH levels after GnRH test tended to be higher, but not significantly,
at 3 months as compared with those obtained with the previous
montly formulation in the same patients (LH: 1.69±0.95 IU/L vs 1.29±0.72
IU/L; FSH: 3.30± 1.88 vs 1.73±0.88 IU/L) and in those children continuing
the montly formulation (LH 1.06±0.85IU/L; FSH 1.77±0.76 IU/L). The peak
FSH and LH decreased thereafter at 6 and 12 months of therapy. Breast stage
was unchanged in 7/11 girls treated with the 3-month depot formulation and
progressed from the stage B2 to B3 in the remaining 4 cases. No modifications
in uterine and ovarian volumes were observed during the study in all patients.
Predicted adult height, CA/BA and HA/BA ratios remained unchanged
respect to those observed during the previous montly injection treatment in both groups of patients.
Conclusion: The 3-month depot formulation of 11.25 mg leuprorelin, efficiently
maintains the gonadal suppression induced by 1-month depot formulation.
The FSH and LH levels tended to be higher in the first months of therapy
compared with those observed during the montly injection regimen but they
do not seem influence negatively the patients bone age and predicted adult
height in the first year of therapy.