Sequential comparisons of one-month and three-month depot leuprolide regimens in central precocious puberty.
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.


OBJECTIVE
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-wk 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 wk) for a minimum of 24 wk. In subjects with DL-stimulated LH 2 IU/liter or less, the dose was changed to 3.75 mg every 4 wk and evaluated 12 wk later. Subjects who met LH criteria (<4.5 IU/liter) on 3.75 mg then received a single dose of 11.25 mg-3 month and were reevaluated 12 wk later. Serum LH/FSH and sex steroids were obtained 40 min after DL injection.


RESULTS
Thirty subjects were enrolled (20 naive; 24 girls, 6 boys), 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 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 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- 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.
Badaru
Angela
A
Division of Pediatric Endocrinology and Diabetes, Stanford University, Stanford, California 94305, USA.
Wilson
Darrell M
DM
Bachrach
Laura K
LK
Fechner
Patricia
P
Gandrud
Laura M
LM
Durham
Eileen
E
Wintergerst
Kupper
K
Chi
Carolyn
C
Klein
Karen O
KO
Neely
E Kirk
EK
D002648:Child; D003692:Delayed-Action Preparations; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D012739:Gonadal Steroid Hormones / Q000037:antagonists & inhibitors; D006062:Gonadotropins / Q000037:antagonists & inhibitors; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage* / Q000627:therapeutic use*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011629:Puberty, Precocious / Q000188:drug therapy*; D015203:Reproducibility of Results
D003692:Delayed-Action Preparations; D012739:Gonadal Steroid Hormones; D006062:Gonadotropins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D016729:Leuprolide