Abstract / Summary
Abstract Purpose: Central precocious puberty (CPP) is associated with neurological disorders. Lennox–Gastaut syndrome (LGS) is a severe epileptic encephalopathy characterized by drug-resistant seizures. This study evaluated the efficacy and safety of gonadotropin-releasing hormone agonist (GnRHa) treatment in patients with LGS and coexisting CPP.
Methods: This retrospective study included 40 patients with LGS and CPP who received GnRHa treatment for at least 1 year. Clinical and auxological data, including growth parameters, bone age, hormonal profiles, and antiseizure medication use, were assessed before and during treatment.
Results: GnRHa treatment was initiated at a mean age of 7.71 ± 1.62 years, with an average treatment duration of 3.31 ± 1.50 years. The bone age to chronological age ratio significantly decreased from 1.27 ± 0.21 at baseline to 1.14 ± 0.17 after 27 months and 1.04 ± 0.11 at treatment completion. Height standard deviation score (SDS) decreased modestly during treatment, whereas body mass index (BMI) SDS remained stable. Peak luteinizing hormone (LH) was suppressed during treatment. Predicted adult height (PAH) showed a nonsignificant increase from 152.5 ± 11.5 cm at baseline to 155.1 ± 12.6 cm at the last follow-up. In an exploratory post hoc analysis, patients with hypoxic–ischemic encephalopathy had greater bone age (BA) advancement at diagnosis (BA/chronological age ratio, 1.44 ± 0.37 vs. 1.24 ± 0.16; p = 0.049) and a larger increase in PAH during treatment (14.5 ± 12.3 vs. 0.6 ± 8.2 cm; p = 0.048) than the remainder of the cohort. Menarche occurred at a mean age of 12.95 ± 1.28 years, approximately 1.80 ± 0.52 years after the end of GnRHa treatment.. Antiseizure medication use did not change significantly during the first year of treatment.
Conclusion: GnRHa treatment was associated with sustained pubertal suppression and attenuation of skeletal maturation in patients with LGS and CPP. The greater skeletal maturation observed at diagnosis in the small HIE subgroup suggests potential heterogeneity in CPP presentation according to underlying neurological etiology and warrants confirmation in larger cohorts..