Effects of undernutrition and low energy availability on reproductive functions and their underlying neuroendocrine mechanisms

Endocr J. 2022 Dec 28;69(12):1363-1372. doi: 10.1507/endocrj.EJ22-0426. Epub 2022 Nov 11.


It has been well established that undernutrition and low energy availability disturb female reproductive functions in humans and many animal species. These reproductive dysfunctions are mainly caused by alterations of some hypothalamic factors, and consequent reduction of gonadotrophin-releasing hormone (GnRH) secretion. Evidence from literature suggests that increased activity of orexigenic factors and decreased activity of anorexigenic/satiety-related factors in undernourished conditions attenuate GnRH secretion in an integrated manner. Likewise, the activity of kisspeptin neurons, which is a potent stimulator of GnRH, is also reduced in undernourished conditions. In addition, it has been suggested that gonadotrophin-inhibitory hormone, which has anti-GnRH and gonadotrophic effects, may be involved in reproductive dysfunctions under several kinds of stress conditions. It should be remembered that these alterations, i.e., promotion of feeding behavior and temporary suppression of reproductive functions, are induced to prioritize the survival of individual over that of species, and that improvements in metabolic and nutritional conditions should be considered with the highest priority.

Keywords: Anorexigenic factors; Gonadotrophin-inhibitory hormone; Gonadotrophin-releasing hormone; Kisspeptin; Orexigenic factors.

Publication types

  • Review

MeSH terms

  • Animals
  • Female
  • Gonadotropin-Releasing Hormone*
  • Gonadotropins
  • Humans
  • Hypothalamus / metabolism
  • Kisspeptins / physiology
  • Malnutrition*


  • Gonadotropin-Releasing Hormone
  • Gonadotropins
  • Kisspeptins