Adverse effects of antiepileptic drugs on hormones of the hypothalamic-pituitary-gonadal axis in males: A review


TOXICOLOGY, vol.465, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 465
  • Publication Date: 2022
  • Doi Number: 10.1016/j.tox.2021.153043
  • Journal Name: TOXICOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Aqualine, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, Communication Abstracts, EMBASE, Environment Index, Food Science & Technology Abstracts, International Pharmaceutical Abstracts, MEDLINE, Metadex, Pollution Abstracts, Veterinary Science Database, Civil Engineering Abstracts
  • Keywords: Epilepsy, Antiepileptic drugs, hypothalamic-pituitary-gonadal axis, Adverse reproductive effects, SEXUAL FUNCTION, SODIUM VALPROATE, LUTEINIZING-HORMONE, TESTICULAR FUNCTION, SPERM PARAMETERS, EPILEPSY, MEN, CARBAMAZEPINE, PROLACTIN, SECRETION
  • Anadolu University Affiliated: Yes


The HPG axis is critical in the maintenance of spermatogenesis and sexual function in males. The GnRH-releasing neurons of the hypothalamus are the axis's main hierarchical element. These neurons make connections with different areas of the brain to regulate the release of GnRH. Neurotransmitters have a critical in the connections between these neurons. So, neurotransmitters can inhibit or stimulate the release of GnRH by affecting GnRH-releasing neurons. In neurological disorders, neurotransmitter's activities inevitably change; therefore, these changes can affect the HPG axis via affecting GnRH-releasing neurons, just like in epilepsy. Many investigations have attracted attention to be decreased fertility potential in males with epilepsy. It has been stated that changes in the HPG axis hormone levels have been found in these patients. Moreover, it has also been observed that sperm quality decreased in patients. It has been emphasized that a decrease in sperm quality may be related to both epilepsy and AEDs. It has been shown that AEDs caused decreased sperm quality by impairing the HPG axis, so they act like endocrine-disrupting chemicals. AEDs can affect fertility and cause additive adverse effects in terms of sperm quality together with epilepsy. Therefore, it is crucial to investigate the adverse reproductive effects of AEDs, which are frequently used during reproductive ages, and determine the role of the HPG axis on potential reproductive pathologies.