A Possible Association of Sex Hormone-Binding Globulin with Weight Gain in the Valproic Acid-Treated Female Patients with Epilepsy

Weight gain is a common adverse consequence of treatment with valproic acid. Although a low sex hormone-binding globulin (SHBG) level was shown to be an independent risk factor for the development of metabolic syndrome and type 2 diabetes in the general population, there is presently no data available regarding the association between the SHBG level and valproic acid-induced weight gain. The association between the plasma SHBG level and being overweight was retrospectively investigated in 46 valproic acid-treated and 59 carbamazepine-treated patients with epilepsy. Among the female patients treated with valproic acid, the plasma SHBG levels tended to be negatively correlated with the gap between the body mass index value for each patient and the upper limit of the normal range (adjusted partial regression coefficient = -6.86, P = 0.041), and the SHBG levels were significantly lower in the overweight subjects than in the normal weight subjects (P = 0.001). These associations were not observed among the valproic acid-treated male patients or the carbamazepine-treated male and female patients. The plasma SHBG levels may be therefore associated with being overweight in the valproic acid-treated female patients.