ESPE Abstracts

Background: There is evidence that unstimulated LH concentrations may be appropriate to monitor hormone suppression in children with central precocious puberty (CPP) during treatment with gonadotropin-releasing hormone agonists (GnRHa). Literature suggests that unstimulated LH concentrations <0.3 and >0.8 IU/L are prepubertal and clearly pubertal, respectively. We present secondary analyses of unstimulated LH suppression data from the pivotal trial of the first small-volume, long-acting, subcutaneously administered GnRHa for CPP (FENSOLVI®), with the goal of assessing whether the study drug effectively suppressed unstimulated LH to prepubertal concentrations.

Methods: Sixty-two children (60 girls, 2 boys) with treatment-naïve CPP received 2 doses of 45mg subcutaneous leuprolide acetate at 24-week intervals. Blood samples used to assess unstimulated LH concentrations were taken at screening, baseline, and weeks 4, 12, 20, 24, 36, 44, and 48. LH concentrations were assessed using a validated central Cobas ECLIA assay with a lower limit of detection of 0.1 IU/L.

Results: Proportions of children who achieved unstimulated LH <0.3 and <0.8 IU/L and their mean estradiol (E2) concentrations are summarized in Table 1. Proportions of children with various target unstimulated LH at week 24 are summarized in Table 2.

Conclusions: Across 48 weeks, 77 to 81% of children maintained prepubertal unstimulated LH concentrations throughout treatment. These data indicate that 45mg subcutaneous leuprolide acetate effectively suppressed unstimulated LH to prepubertal concentrations. Additionally, 81% of children with pubertal suppression (stimulated LH <4 IU/L) had unstimulated LH <0.8 IU/L, suggesting that this cutoff may be suitable for monitoring treatment efficacy, especially if considered along with sex hormone levels.