Pubertal development and hormonal modulation in pediatric low-grade gliomas: a retrospective cohort study

Pediatric low-grade gliomas (pLGGs) are the most common brain tumors in children. While overall survival is excellent, tumor progression remains frequent, especially in surgically challenging locations. Puberty brings profound hormonal changes, and growing evidence suggests that sex hormones may influence glioma biology. The impact of pubertal development, including central precocious puberty (CPP), on tumor behavior is not well understood. We performed a retrospective study of 301 children with histologically confirmed pLGGs treated at a single tertiary center from 2015 to 2025. Data collected included clinical, radiological, endocrine, histopathological, and molecular information. Pubertal status was assessed using Tanner staging, and CPP was defined by standard clinical and hormonal criteria. Progression-free survival (PFS) was analyzed according to pubertal stage and, in patients with CPP, by treatment with gonadotropin-releasing hormone (GnRH) analogues. Kaplan–Meier curves and log-rank tests were used for survival analysis. Advanced pubertal development (Tanner stage > 3) was observed in 112 patients (37%), and 18 patients (6%) met criteria for CPP. Nearly all children with CPP had tumors involving the diencephalic or hypothalamic–optic pathway. Among patients with CPP, those treated with GnRH analogues (n = 13) had significantly longer PFS than untreated patients (n = 5) (p = 0.00038), with 60-month PFS of 78% versus 25%. Tumor progression after stopping GnRH therapy often coincided with pubertal reactivation. Compared with age-matched children without CPP, GnRH therapy showed a trend toward longer PFS, though not statistically significant (p = 0.10). Pubertal development and CPP are strongly associated with hypothalamic–optic pathway pLGGs and may influence tumor behavior in a subset of patients. In children with CPP, hormonal suppression with GnRH analogues was associated with prolonged PFS, supporting a potential modulatory role of endocrine signaling in pLGGs. These findings underscore the importance of systematic monitoring of pubertal development and warrant prospective studies to clarify the role of endocrine modulation within multimodal treatment strategies for pediatric low-grade glioma. Pubertal stage is associated with modulation of the clinical course of pediatric low-grade gliomas. In children with central precocious puberty, treatment with GnRH analogues is associated with improved progression-free survival. Hormonal status and tumor location emerge as clinically relevant determinants of prognosis and should be considered in patient assessment and treatment planning.