Unstimulated Luteinizing Hormone for Assessment of Suppression during Treatment of Central Precocious Puberty with 6-Month Subcutaneous Leuprolide Acetate: Correlations with Clinical Response

Abstract

Introduction: Phase 3 trial of 6-month subcutaneous leuprolide acetate (SC-LA) in children with central precocious puberty (CPP) demonstrated efficacy and safety. Aims of this secondary analysis: evaluate unstimulated luteinizing hormone (LH) as efficacy measure; assess clinical suppression metrics; and present biochemical and clinical data for subgroups not achieving hormone suppression. Methods: 62 children with treatment-naïve CPP received 2 doses of 45 mg SC-LA at 24-week intervals. Unstimulated and GnRH-stimulated LH, E2, and T concentrations were measured. Clinical measures included bone age (BA) and predicted adult height (PAH). Results: 84% and 86% of children achieved unstimulated LH<1IU/L at weeks 24 and 48, respectively. Of 8 children not achieving unstimulated LH<1IU/L at week 24 that completed the study, all showed lack of pubertal stage progression and stable/decreased BA to chronological age ratio (BA/CA). Received operating characteristic (ROC) analyses suggested unstimulated LH is a good diagnostic predictor of GnRH-stimulated LH<4IU/L at week 24 and 48 (AUC=0.88). Across all children, mean BA/CA improved from 1.4 (screening) to 1.3 (week 48) and mean PAH increased by 3cm. Of 7 girls not achieving stimulated LH<4IU/L at week 24, all achieved E2<10pg/mL, showed lack of pubertal stage progression, and had stable or decreased BA/CA by week 48. Additionally, 6/7 had increased PAH by week 48 and 4 had unstimulated LH<1IU/L. Conclusion: Unstimulated LH has value as an efficacy measure and concentrations <1IU/L may be an adequate surrogate of treatment response in children with CPP. All children who completed the study had evidence of pubertal suppression.