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O-8 Kisspeptina new era in sports endocrinology?
  1. Craig Wayne Grobbelaar1,
  2. Robert Peter Millar1,2,3,4
  1. 1Department of Physiology, University of Pretoria, South Africa
  2. 2Centre for Neuroendocrinology and Mammal Research Institute, University of Pretoria, Pretoria
  3. 3UCT/MRC Receptor Biology Unit, Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa
  4. 4Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK

Abstract

Athletic Amenorrhoea is a fairly common and invariably performance-limiting condition seen in female endurance athletes, dancers and gymnasts, notably those of the “low body weight” genera (up to 60% are affected). The hypothalamic amenorrhoea in athletes exists as a continuum preceded by a stressor exercise stress; reduced energy availability) followed by lowered gonadotropin releasing hormone (GnRH) stimulation, diminished gonadotropic hormone release, finally resulting in reduced steroid hormone production. The treatment of athletic amenorrhoea focuses largely on reversing the energy imbalance, reducing training and, if necessary supplementing with exogenous sex steroids. The latter proves less popular for use in younger athletes. Gonadotropin administration has thus far been the treatment of choice to restore reproductive function.

The use of androgenic anabolic steroids (AAS), synthetic derivatives of testosterone, has been the subject of concern in the sporting industry for decades. AAS’s have been shown to enhance androgen receptor expression in the hypothalamus, thus invoking a negative feedback response on GnRH and luteinizing hormone (LH) release giving rise to anabolic steroid-induced hypogonadism (ASIH). This diminution in gonadotrophic activity has been shown to have a deleterious effect on sexual behaviour and reproduction in both animal and human models. Various case studies have been presented to highlight the long term consequences of both clinical and aberrant supraphysiological doses of exogenous steroids as seen in chronic users and abusers. The treatment of ASIH entails restoration of the hypothalamic-pituitary-testicular axis (HPT) to re-establish endogenous testosterone production and action. Thus the increased use of AAS’s in adolescents and young adults have highlighted the need for control. The control hereof does not only seek to negate the in-competition advantage in athletes but to deter the sometimes irreversible behavioural and reproductive dysfunction encountered in users.

Kisspeptins are a group of peptidergic neurohormones that are able to stimulate the hypothalamic-pituitary-gonadal (HPG) axis and the secretion of GnRH, LH, follicle stimulating hormone (FSH), estradiol and testosterone in a dose-dependent manner. They act via the G-protein coupled receptor ((GPR-54); (KISS1R)) and are encoded by the KISS1 gene. Overtraining and reduced calorie intake in athletic females and anabolic steroid use has been shown to diminish LH pulse frequency and secretion via the diminution of GnRH expression. Studies done in males and females with hypothalamic hypogonadism who received intravenous and subcutaneous kisspeptin analogues showed a dose dependent increase in mean LH and LH pulse frequency. Kisspeptin administration has been shown to maintain 2-fold elevations in LH secretion despite elevated testosterone in males. Therefore, it is proposed that exogenous administration of Kisspeptin should yield an increase in LH secretion and pulsatility to a much greater extent. This has staggering implications, as kisspeptin could possibly be used in provocative testing with regards to the use of AAS in athletes. It is likely that Kisspeptin administration will restore LH pulsatility in these athletes and reverse the hypogonadism and effects thereof, thus offering a newer treatment option. This allows for a novel therapeutic mechanism by which the effects of athletic and steroid-induced hypogonadism can be corrected.

References

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  • androgenic anabolic steroids
  • athletic amenorrhea
  • hypogonadism
  • kisspeptin

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