Alterations in semen parameters in men wıth epilepsy treated with valproate

  • Hatice Kose-Ozlece Mail Department of Neurology, School of Medicine, Kafkas University Medical Faculty, Kars, Turkey
  • Faik Ilık Department of Neurology, School of Medicine, Mevlana University, Konya, Turkey
  • Kursat Cecen Department of Urology, School of Medicine, Kafkas University Medical Faculty, Kars, Turkey
  • Nergiz Huseyınoglu Department of Neurology, School of Medicine, Kafkas University Medical Faculty, Kars, Turkey
  • Ataman Serım Department of Neurology, School of Medicine, Kafkas University Medical Faculty, Kars, Turkey
Valproate, Male Infertility, Epilepsy, Antiepileptic Drugs, Reproductive Dysfunction


Background: Besides the well-known adverse effects of valproate (VPA), disorders related to male reproductive functions have been reported. Furthermore, only a limited number of previous studies have reported the relationship between VPA dose and impairment of the hormonal axis and semen quality. A patient with reversible changes that occurred in the sperm parameters after a dose increment of VPA.
Methods: A 34-year-old male patient who was diagnosed with juvenile myoclonic epilepsy almost 15 years ago was admitted to our clinic. His seizures responded well to high doses of VPA treatment.
Results: As the VPA dose was increased, consecutive semen analyses were performed and averaged for each dose; the results showed a remarkable decline in the sperm count and a manifest loss of sperm motility. VPA treatment was gradually diminished and stopped; meanwhile, treatment with another antiepileptic (lamotrigin) was initiated to control the patient’s seizures. Nine months later, the patient’s semen analysis was within normal ranges. After modification of the patient’s treatment regimen, he and his wife had a healthy baby.
Conclusion: We suggest that VPA-dependent impairments in the hormone and semen analysis parameters were reversible after the termination of medical treatment, and that the VPA treatment did not cause permanent hormonal deregulation and, these side effects are dose dependent.


1. Roste LS, Tauboll E, Haugen TB, Bjornenak T, Saetre ER, Gjerstad L. Alterations in semen parameters in men with epilepsy treated with valproate or carbamazepine monotherapy. Eur J Neurol 2003; 10(5): 501-6.
2. Loscher W. Basic pharmacology of valproate: a review after 35 years of clinical use for the treatment of epilepsy. CNS Drugs 2002; 16(10): 669-94.
3. Chen SS, Shen MR, Chen TJ, Lai SL. Effects of antiepileptic drugs on sperm motility of normal controls and epileptic patients with long-term therapy. Epilepsia 1992; 33(1): 149-53.
4. Isojarvi JI, Lofgren E, Juntunen KS, Pakarinen AJ, Paivansalo M, Rautakorpi I, et al. Effect of epilepsy and antiepileptic drugs on male reproductive health. Neurology 2004; 62(2): 247-53.
5. Xiaotian X, Hengzhong Z, Yao X, Zhipan Z, Daoliang X, Yumei W. Effects of antiepileptic drugs on reproductive endocrine function, sexual function and sperm parameters in Chinese Han men with epilepsy. J Clin Neurosci 2013; 20(11): 1492-7.
6. Sveberg RL, Tauboll E, Berner A, Berg KA, Aleksandersen M, Gjerstad L. Morphological changes in the testis after long-term valproate treatment in male Wistar rats. Seizure 2001; 10(8): 559-65.
7. World Health Organization. WHO Laboratory Manual for the Examination and Processing of Human Semen. Geneva, witzerland: World Health Organization, 2010.
8. Kruger TF, Menkveld R, Stander FS, Lombard CJ, Van der Merwe JP, van Zyl JA, et al. Sperm morphologic features as a prognostic factor in in vitro fertilization. Fertil Steril 1986; 46(6): 1118-23.
9. Menkveld R, Lacquet FA, Kruger TF, Lombard CJ, Sanchez Sarmiento CA, de VA. Effects of different staining and washing procedures on the results of human sperm morphology evaluation by manual and computerised methods. Andrologia 1997; 29(1): 1-7.
10. Phiel CJ, Zhang F, Huang EY, Guenther MG, Lazar MA, Klein PS. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem 2001; 276(39): 36734-41.
11. Dada R, Kumar M, Jesudasan R, Fernandez JL, Gosalvez J, Agarwal A. Epigenetics and its role in male infertility. J Assist Reprod Genet 2012; 29(3): 213-23.
12. Tung EW, Winn LM. Valproic acid increases formation of reactive oxygen species and induces apoptosis in postimplantation embryos: a role for oxidative stress in valproic acid-induced neural tube defects. Mol Pharmacol 2011; 80(6): 979-87.
13. Jodar M, Oliva R. Protamine alterations in human spermatozoa. Adv Exp Med Biol 2014; 791: 83-102.
14. Isojarvi JI, Tauboll E, Herzog AG. Effect of antiepileptic drugs on reproductive endocrine function in individuals with epilepsy. CNS Drugs 2005; 19(3): 207-23.
15. Roste LS, Tauboll E, Morkrid L, Bjornenak T, Saetre ER, Morland T, et al. Antiepileptic drugs alter reproductive endocrine hormones in men with epilepsy. Eur J Neurol 2005; 12(2): 118-24.
16. Rattya J, Turkka J, Pakarinen AJ, Knip M, Kotila MA, Lukkarinen O, et al. Reproductive effects of valproate, carbamazepine, and oxcarbazepine in menith epilepsy. Neurology 2001; 56(1): 31-6.
17. Yerby MS, McCoy GB. Male infertility: possible association with valproate exposure. Epilepsia 1999; 40(4): 520-1.
18. Hayashi T, Yoshida S, Yoshinaga A, Ohno R, Ishii N, Yamada T. Improvement of oligoasthenozoospermia in epileptic patients on switching anti-epilepsy medication from sodium valproate to phenytoin. Scand J Urol Nephrol 2005; 39(5): 431-2.
How to Cite
Kose-Ozlece H, Ilık F, Cecen K, Huseyınoglu N, Serım A. Alterations in semen parameters in men wıth epilepsy treated with valproate. Curr J Neurol. 14(3):164-167.
Special Articles