Can valproic acid treatment affect male fertility?/nThe question is asked by a patient to his healt

Fråga: Can valproic acid treatment affect male fertility? The question is asked by a patient to his health-care provider. There is no obvious clinical history of infertility.

Sammanfattning: There is no solid basis for concluding that valproic acid is a general cause of decreased fertility in epileptic patients. However, there are some empirical observations and perhaps theoretical reasons to suspect that in some patients, valproic acid may negatively affect sperm count and quality. In case of established infertility in a male patient treated with valproic acid, a change of drug regime may be contemplated.

Svar: Men with epilepsia has a significantly lower fertility rate than in the general population. Hyposexuality and reduced potency is reported in 38-71% of patients. Animal studies have shown altered semen quality after use of a variety of anticonvulsants, including phenytoin, carbamazepine and valproic acid (1).

The role of antiepileptic drugs in the reduced fertility of epileptic men is at present not clear. No trials of the relative frequency of infertility in treatment with different antiepileptic agents could be identified. Two studies describe a higher frequency of altered sperm morphology in epileptic patients treated with carbamazepine, oxcarbamazepine or valproic acid, compared with healthy (non-epileptic) controls (1,2). However, carbamazepine and valproic acid are expected to have opposite effects on the exposure to endogenous sex hormones, with carbamazepine lowering androgen exposure, and valproic acid possibly elevating it (3). The strategy of elevating androgen exposure in order to achieve azospermia through decreased gonadotropin levels has been tried for male contraception (4). Evidence for altered gonadotropin levels due to valproic acid therapy, however, are not consistent (3,5,6).

There are a few case reports of oligospermia and infertility in patients treated with valproic acid, which was reversible on discontinuation of the drug (7,8). However, improvement of sperm count and motility has also been reported in switching drug therapy from phenytoin to valproic acid (9).