Valproate-induced hyperandrogenism during pubertal maturation in girls with epilepsy

Valproate is effective for treatment of a variety of seizure types both in adults and in children with epilepsy, but it induces obesity and polycystic ovaries in a considerable proportion of adult women, particularly when the medication is started before the age of 20. In the present study we evalua ted reproductive endocrine function in 41 girls, 8 to 18 years old, taking valproate for epilepsy and in 54 healthy control girls. Among the girls tak ing valproate, 16 were prepubertal, 11 were pubertal, and 14 were postpuber tal, and the corresponding numbers were 20, 13, and 21 in the control group . The mean serum testosterone concentrations of prepubertal, pubertal, and postpubertal girls taking valproate were significantly higher than those of the control girls at the same pubertal stage, Hyperandrogenism, defined as serum testosterone levels higher than the mean + 2SD in the control girls at the same pubertal stage, was seen in 38% of prepubertal, 36% of pubertal , and 57% of postpubertal girls taking valproate. In addition, postpubertal girls taking valproate were more obese than the controls and the mean seru m insulin-like growth factor binding protein-1 concentration of pubertal an d postpubertal hyperandrogenic girls taking valproate was lower than in val proate-treated girls without hyperandrogenism. Valproate may induce hyperan drogenism in girls with epilepsy during the sensitive period of pubertal ma turation, and the frequency of hyperandrogenism increases with pubertal dev elopment. This emphasizes the importance of careful endocrine observation o f girls taking valproate for epilepsy.