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

Toxicology. 2022 Jan 15:465:153043. doi: 10.1016/j.tox.2021.153043. Epub 2021 Nov 17.

Abstract

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.

Keywords: Adverse reproductive effects; Antiepileptic drugs; Epilepsy; hypothalamic–pituitary–gonadal axis.

Publication types

  • Review

MeSH terms

  • Animals
  • Anticonvulsants / adverse effects*
  • Endocrine Disruptors / adverse effects*
  • Gonadal Steroid Hormones / metabolism
  • Gonadotropin-Releasing Hormone / metabolism
  • Hormones / metabolism*
  • Humans
  • Hypothalamo-Hypophyseal System / drug effects*
  • Hypothalamo-Hypophyseal System / metabolism
  • Hypothalamo-Hypophyseal System / physiopathology
  • Infertility, Male / chemically induced*
  • Infertility, Male / metabolism
  • Infertility, Male / physiopathology
  • Male
  • Reproduction / drug effects*
  • Risk Assessment
  • Risk Factors
  • Spermatogenesis / drug effects
  • Spermatozoa / drug effects
  • Spermatozoa / metabolism
  • Spermatozoa / pathology
  • Testis / drug effects*
  • Testis / metabolism
  • Testis / physiopathology

Substances

  • Anticonvulsants
  • Endocrine Disruptors
  • Gonadal Steroid Hormones
  • Hormones
  • Gonadotropin-Releasing Hormone