The effects of epilepsy and/or valproate (VPA) monotherapy on physical growth, weight gain, pubertal development, and hormonal status of 68 consecutive female patients aged 6-20 years (20 premenarche, 60 postmenarche) were studied at the Institute for Endocrinology and Diabetes, Schneider Children's Medical Center, and Tel Aviv University, Israel. Two groups of patients, 45 during long-term treatment with VPA and 43 before treatment was initiated, were compared. Treated postmenarcheal patients had a higher mean testosterone level than untreated controls (p=0.006). Body mass index-standard deviation scores were not increased. Rates of obesity were not significantly different in treated and untreated groups, 16.3% and 15.5%, respectively. Menses irregularities, hirsutism, and acne occurred with equal frequency in the 2 groups. The treated group had higher levels of thyroid-stimulating hormone and lower levels of free thyroxine than the untreated group, but both were within the normal range. [1]

COMMENT. Long-term treatment with valproate in girls with epilepsy results in increased testosterone levels after menarche, without signs of hyperandrogenism, polycystic ovary syndrome, or increase in body mass index. Endocrine function should still be monitored if valproate is prescribed for epilepsy in adolescent girls. Other studies have linked obesity, hyperinsulinemia, hyperandrogenism, and polycystic ovaries with long-term valproate therapy for epilepsy in women [2]. Epileptic and neurologic factors, and not valproate, have been cited as the primary cause of polycystic ovary syndrome [3]. Valproate should be avoided if possible in women of childbearing age and during pregnancy, given the high rate of associated fetal malformations, neonatal neurobehavioral and late neurological side effects [4].