Valproate-associated reproductive hormone abnormalities: do bipolar men have the same risk as epileptic men?

The effects of valproate on male reproductive hormones have been studied in epileptic patients and animals, but the results are inconsistent because reproductive hormone abnormalities may be independent of the use of valproate and may be due to epilepsy itself. The aim of this study was to determine if there is an association between valproate and reproductive abnormalities in men with bipolar disorder or if the association is unique to men with epilepsy.

The study included 39 male patients aged 18-50 years with a DSM-IV diagnosis of bipolar disorder (21 on lithium monotherapy and 18 on valproate monotherapy or valproate in combination with lithium therapy) and 15 male epilepsy patients on valproate monotherapy that were evaluated in terms of reproductive hormones.

Duration of illness, duration of lithium and valproate therapy, daily dose and serum concentrations of lithium and valproate, duration of marriage, spouse's gravidity, the serum estradiol, luteinizing hormone, sex hormone-binding globulin, and free testosterone levels, and the free testosterone:luteinizing hormone ratio were not significantly different between the groups. Serum prolactin and follicle-stimulating hormone levels were significantly higher in the epilepsy patients than in the bipolar disorder patients on lithium monotherapy.

The findings show that valproate did not have a negative effect on male reproductive hormones in the bipolar patients. The elevated prolactin and follicle-stimulating hormone levels observed in the epilepsy group should be attributed to epilepsy. To the best of our knowledge this is the first study to compare reproductive hormones in bipolar disorder and epilepsy patients on valproate therapy.