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Effect of epilepsy and antiepileptic drugs on male reproductive health

From the Departments of Neurology (Drs. Isojärvi and Löfgren), Clinical Chemistry (Dr. Pakarinen), and Radiology (Dr. Päivänsalo), University of Oulu, and Infertility Clinic of the Family Federation of Finland (Drs. Tuomivaara and Juntunen), Oulu, and Department of Neurology (Dr. Rautakorpi), Lapland Central Hospital, Rovaniemi, Finland.

Address correspondence and reprint requests to Dr. J.I.T. Isojärvi, Department of Neurology, P.O. Box 5000, FIN-90014 University of Oulu, Oulu, Finland; e-mail: jouko.isojarvi{at}oulu.fi

Background: Men with epilepsy have reduced fertility, and antiepileptic drugs may affect semen quality. Moreover, animal studies suggest that valproate (VPA) may be associated with testicular atrophy.

Objective: To evaluate reproductive function in men with epilepsy.

Methods: Sixty men with epilepsy and 41 control men were evaluated for their reproductive health. Fifteen men were taking carbamazepine (CBZ) and 18 men oxcarbazepine (OXC) for partial epilepsy, and 27 men were taking VPA for generalized epilepsy. Reproductive hormones were assayed from serum samples, semen analysis and ultrasonography of the testicles were performed, and testicular volume was calculated.

Results: Men on CBZ had low serum dehydroepiandrosterone sulfate concentrations (p < 0.001), and men on VPA had high concentrations of serum androstenedione (p < 0.001). The frequency of morphologically abnormal sperm was higher among CBZ-treated (p < 0.01), OXC-treated (p < 0.05), and VPA-treated men (p < 0.01) than among the control men. Moreover, both CBZ and VPA were associated with poor motility of sperm (p < 0.05). In addition, the frequency of abnormally low sperm concentration was high in men on CBZ (p < 0.001), and the frequency of any sperm abnormality was high in men on VPA (p < 0.01). The VPA-treated men with abnormal sperm had smaller testicular volumes than the control men (p = 0.003).

Conclusions: CBZ, OXC, and VPA are associated with sperm abnormalities in men with epilepsy. In addition, VPA-treated men with generalized epilepsy who have abnormal sperm may have reduced testicular volume.

Received December 18, 2001. Accepted in final form September 5, 2003.

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