Sleep, testosterone and cortisol balance, and ageing men

Rev Endocr Metab Disord. 2022 Dec;23(6):1323-1339. doi: 10.1007/s11154-022-09755-4. Epub 2022 Sep 24.


Sleep serves important biological functions, and influences health and longevity through endocrine and metabolic related systems. Sleep debt, circadian misalignment and sleep disruption from obstructive sleep apnea is widespread in modern society and accumulates with life because recovery sleep is not completely restorative. Accumulated disordered sleep throughout life impacts the ageing process and the development of age-related diseases. When epidemiological and interventional studies are considered collectively, sleep loss and lower sleep duration are associated with lower morning, afternoon and 24-h testosterone; as well as higher afternoon, but not morning or 24-h cortisol. These reciprocal changes imbalances anabolic-catabolic signaling because testosterone and cortisol are respectively the main anabolic and catabolic signals in man. Fixing testosterone-cortisol balance by means of a novel dual-hormone clamp mitigates the induction of insulin resistance by sleep restriction and provided the first proof-of-concept that the metabolic harm from sleep loss can be ameliorated by approaches that do not require sleeping more. Obstructive sleep apnea is associated with lower testosterone, even after controlling for age and obesity whereas the conclusion that continuous positive airway pressure therapy has no effect on testosterone is premature because available studies are underpowered and better-quality studies suggest otherwise. High dose testosterone therapy induces OSA, but more physiological dosing may not; and this effect may be transient or may dissipate with longer term therapy. Studies investigating the origin of the diurnal testosterone rhythm, the effect of circadian misalignment on testosterone-cortisol balance, and methods to mitigate metabolic harm, are required.

Keywords: Androgen; Cardiometabolic health; Circadian; Glucocorticoid; Sleep disordered breathing.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging
  • Humans
  • Hydrocortisone / metabolism
  • Male
  • Sleep / physiology
  • Sleep Apnea, Obstructive* / etiology
  • Sleep Apnea, Obstructive* / therapy
  • Testosterone* / metabolism


  • Testosterone
  • Hydrocortisone