Valproic Acid Metabolism and its Consequences on Sexual Functions

Curr Drug Metab. 2016;17(6):573-81. doi: 10.2174/1389200217666160322143504.


Background: Valproic acid (VPA) is a broad spectrum antiepileptic drug (AED) that is generally regarded as a first-choice agent for most forms of idiopathic and symptomatic generalised epilepsies. Available data suggest that menstrual disorders and certain endocrine manifestations of reproductive system disorders may be more common in women treated with VPA than in those treated with other AEDs.

Methods: A PubMed search for MEDLINE was undertaken to look for studies using the terms "VPA metabolism", "VPA and sexual functions in men", "VPA and sexual functions in women" and "VPA metabolism and endocrine disorders" as key words. The period covered was approximately 20 years.

Results: In women, VPA medication is associated with hyperandrogenism, polycystic ovary/polycystic ovarian syndrome, menstrual disorders and ovulatory failure. Men on VPA therapy show abnormalities in androgens blood levels, sperm motility and erectile dysfunctions. VPA negatively affects the release of luteinizing hormone, follicle stimulating hormone and prolactin but also the drug interferes in peripheral endocrine hormones. Its broad inhibitory action on cytochrome and glucuronidation systems can lead to high serum concentration of testosterone, androstenedione and dehydroepiandrosterone sulfate. VPA-dependent obesity and hyperinsulinemia can further contribute to an increase in sexual dysfunctions.

Conclusions: VPA interferes with the endocrine system at multiples levels causing several reproductive and sexual dysfunctions in women and men with epilepsy, especially when administered in pubertal age. Since VPA is a first line AED both in children and adult with epilepsy and long-term medication with this drug is sometimes necessary, it is very important for physicians to implement strict monitoring of patients taking VPA in order to identify these kinds of side effects at an early stage.

Publication types

  • Review

MeSH terms

  • Animals
  • Anticonvulsants / adverse effects*
  • Anticonvulsants / pharmacokinetics
  • Biotransformation
  • Endocrine System / drug effects*
  • Endocrine System / metabolism
  • Endocrine System / physiopathology
  • Endocrine System Diseases / chemically induced*
  • Endocrine System Diseases / metabolism
  • Endocrine System Diseases / physiopathology
  • Female
  • Humans
  • Male
  • Reproduction / drug effects*
  • Risk Factors
  • Sexual Behavior / drug effects*
  • Sexual Dysfunction, Physiological / chemically induced*
  • Sexual Dysfunction, Physiological / metabolism
  • Sexual Dysfunction, Physiological / physiopathology
  • Valproic Acid / adverse effects*
  • Valproic Acid / pharmacokinetics


  • Anticonvulsants
  • Valproic Acid