Evaluation of the effects of antiepileptic monotherapy on pubertal hormones in adolescent girls with epilepsy

Background Epilepsy often begins in childhood or adolescence, a period marked by significant hormonal changes. Antiepileptic drugs (AEDs) like valproic acid (VPA) and levetiracetam (LEV) are commonly used, but VPA is associated with notable endocrine side effects, particularly in adolescent girls. This raises concerns about drug choice during puberty. Objective To compare the effects of VPA and LEV monotherapy on pubertal hormone profiles, menstrual characteristics, physical development, and gynecologic ultrasound findings in adolescent girls with primary epilepsy. Methods This prospective, cross‐sectional study included 61 adolescent girls (16 on VPA, 15 on LEV, 30 controls) at a tertiary hospital from January 2018 to January 2019. Participants underwent anthropometric measurements, hormonal evaluations (FSH, LH, estradiol, testosterone, SHBG, TSH, 17‐OH progesterone, DHEASO 4 ), menstrual assessments, and pelvic ultrasound. Statistical analysis was performed with a significance level of p < 0.05. Results VPA users had significantly higher TSH levels than LEV users and controls ( p = 0.036), suggesting possible subclinical thyroid dysfunction. They also had lower 17‐OH progesterone and DHEASO 4 levels ( p = 0.008 and p = 0.022, respectively). No significant differences were observed between groups in weight, height, BMI, pubertal hormone levels, menstrual cycle characteristics, or ultrasound findings. Treatment duration did not significantly affect hormone levels. Conclusion VPA appears to negatively impact thyroid and adrenal hormones in adolescent girls, whereas LEV has a safer endocrine profile. Given the hormonal sensitivity during puberty, LEV may be a safer alternative for adolescent girls with epilepsy to reduce potential endocrine disturbances.