Background: Dosing of monthly depot leuprolide (DL) in central precocious puberty (CPP) varies considerably. U.S. practitioners use 7.5-15 mg, in contrast with the international standard of 3.75 mg. Pubertal suppression using the newer 3-month DL also has been reported from Europe. To date there have been no direct comparisons of these different DL doses.

Objectives: In an open 12 month protocol we tested the efficacy of three DL doses (7.5 mg- and 3.75 mg-1 month and 11.25 mg-3 month) given sequentially to subjects treated for CPP. Primary outcome measures were stimulated gonadotropin (Gn) levels at 12 week intervals. The null hypothesis was no difference among doses.

Methods: Both existing and new patients with CPP received our standard therapy (DL 7.5 mg every 4 weeks) for a minimum of 24 weeks. In subjects with DL-stimulated LH (LH) 2 IU/L, the dose was changed to 3.75 mg every 4 weeks and evaluated 12 weeks later. Subjects who met LH criteria (< 4.5 IU/L) on 3.75 mg then received a single dose of 11.25 mg-3 month and were reevaluated 12 weeks later. Serum LH/follicle stimulating hormone (FSH) and sex steroids were obtained 40 min after DL injection.

Results: 30 subjects were enrolled (20 naive; 24/6 female/male), and 21 were evaluated on all three DL doses. DL-stimulated LH levels (mean ± SD) were 1.30 ± 0.74, 1.73 ± 0.99 and 2.13 ± 1.41 on 7.5 mg, 3.75 mg and 11.25 mg-3 month, respectively (7.5 mg vs. 3.75 mg, P = 0.019; 7.5 mg vs. 11.25 mg-3 month, P = 0.004, Wilcoxon ranked sign test). Mean FSH levels were 2.86 ± 1.91, 3.91 ± 1.98 and 3.96 ± 1.34 respectively (7.5 mg vs. 3.75 mg, P = 0.017; 7.5 mg vs. 11.25 mg-3 month, P = 0.020). No differences were detected in mean sex steroid levels.

Conclusions: Stimulated LH and FSH levels were significantly higher during therapy with both the 3.75 mg and 11.25 mg-3 month depot leuprolide doses compared with 7.5 mg, contradicting the null hypothesis of no difference. These data suggest that low dose 1-month and 3-month DL preparations are associated with persistently greater gonadal stimulation in most CPP patients, but the LH/FSH results were not corroborated by differences in sex steroid levels. Whether various DL doses lead to long-term therapeutic differences remains to be determined.