Age at onset of puberty following high-dose central nervous system radiation therapy

Objective: To determine if a relationship exists between age at irradiation, sex of the patient, and age at onset of puberty and pubarche in children treated with high-dose radiation to the central nervous system. Design: Case series. Setting: Tertiary care institutional practices and clinics. Patients: Thirty-six children treated with high-dose irradiation (hypothalamic pituitary dose, 30-72 Gy) by conventional (n=29) or hyperfractionated (n=7) schedules. Girls were treated before age 8 years and boys before age 9 years. Twenty-six of the 36 children also received chemotherapy. All tumors were distant from the hypothalamic-pituitary region. Main Outcome Measure: Age at onset of puberty and pubarche. Results: In girls, the median age at onset of puberty was 9.3 years vs 10.9 years for controls (P<.01); pubarche occurred at 9.4 years vs 11.2 years for controls (P<.01). In boys, the median age at onset of puberty-genital II-was 11.0 years vs 11.5 years for controls (P=.30); pubarche occurred at a median age of 10.5 years vs 12 years for controls (P=.25). A censored-data normal linear regression model was used to account for children (n=6) who had not reached puberty. Age at diagnosis (P<.01) and sex (P=.01) were significant predictors of age at onset of puberty. Body mass index SD score (z score) was inversely related to age at onset of puberty (r=-0.77) and was greater at onset of puberty in girls than in boys. Conclusion: In children who have received high-dose cranial radiation therapy, a significant positive correlation exists between age at diagnosis and age at onset of puberty in boys and girls.