The effects of valproate, carbamazepine, and oxcarbazepine on growth and sexual maturation in girls with epilepsy

Objective. Antiepileptic drugs (AEDs) have endocrine effects that may inter fere with growth and sexual maturation in children. The aim of this study w as to evaluate the effects of AEDs on growth and pubertal development in gi rls with epilepsy. Study Design. Forty girls taking valproate (VPA), 19 girls taking carbamaze pine (CBZ), and 18 girls taking oxcarbazepine (OXC) for epilepsy and 49 hea lthy control girls participated in the study, which included a cross-sectio nal clinical examination when the girls were 8 to 18 years old and a longit udinal growth analysis from the age of 1 year. Results. VPA, CBZ, or OXC did not affect linear growth or pubertal developm ent in girls with epilepsy. However, the patients taking VPA gained weight, and an increase in relative weight was seen in girls who started their med ication before as well as during puberty. The body mass index of the VPA-tr eated girls (19.8 +/- 4.8 kg/m(2)) was higher than that of the control girl s (18.0 +/- 2.5 kg/m2) at clinical examination. The weight of the girls tak ing CBZ or OXC for epilepsy was similar to that of the control girls. Plasm a insulin-like growth factor-I (IGF-I) levels were higher in girls treated with CBZ and OXC than in the control girls, but AEDs did not affect fasting serum insulin, IGF-binding protein-1, or IGF-binding protein-3 concentrati ons in girls on VPA, CBZ, or OXC medication during the period of exposure ( average 2.8, 4.1, and 1.9 years, respectively) in this study. Conclusions. AEDs do not seem to have any adverse effects on linear growth or sexual maturation in girls with epilepsy. VPA-related weight gain can be seen already in prepuberty and it is not associated with hyperinsulinemia in these young patients. The clinical significance of high circulating conc entrations of IGF-I in patients taking CBZ or OXC remains to be defined.