We evaluated the effects of carbamazepine (CBZ) on serum androgen levels and sexual function prospectively for 5 years in 11 men with epilepsy and in 25 patients receiving either CBZ (14 patients) or phenytoin (PHT) (11) monotherapy for > 5 years. Serum sex hormone binding globulin (SHBG) levels increased and free androgen index (FAI) decreased during CBZ treatment, and these changes correlated with duration of CBZ therapy. Similarly, serum SHBG levels increased and FAI values decreased in patients receiving PHT for > 5 years. CBZ and PHT increase serum SHBG levels, leading to decreased FAI. These drug-related hormonal changes may be the primary cause of hyposexuality common in men with epilepsy.