VALPROATE, LAMOTRIGINE, AND INSULIN-MEDIATED RISKS IN WOMEN WITH EPILEPSY

We recently reported the frequent occurrence of polycystic ovaries and hyperandrogenism associated with weight gain and hyperinsulinemia in women taking valproate for epilepsy. The purpose of this study was to evaluate the risks related to valproate-induced hyperinsulinemia and t heir reversibility after discontinuing the medication. Sixteen women w ith valproate-related polycystic ovaries or hyperandrogenism participa ted in the study. Vaginal ultrasonography was performed, and endocrine and lipid parameters were measured. Thereafter, lamotrigine was subst ituted for valproate and the patients were observed for 12 months. Twe nty-four healthy age-matched women sen ed as control subjects. Twelve women completed the 12-month follow-up. While still on valproate they had centripetal obesity with associated hyperinsulinemia and unfavorab le serum lipid profiles. The body-mass index and fasting serum insulin and testosterone concentrations decreased during the first year after replacing valproate with lamotrigine whereas the HDL-cholesterol/tota l cholesterol ratios increased from 0.17 +/- 0.06 to 0.26 +/- 0.05. Th e total number of polycrystic ovaries in these women decreased from 20 during valproate medication to 11 one year after replacing valproate with lamotrigine. Valproate induces a metabolic syndrome with centripe tal obesity, hyperinsulinemia, lipid abnormalities, and polycystic ova ries/hyperandrogenism in women with epilepsy. These valproate-related risks can be reduced by substituting lamotrigine for valproate.