The association between the cortisol and cortisone awakening responses

Psychoneuroendocrinology. 2023 Jun:152:106075. doi: 10.1016/j.psyneuen.2023.106075. Epub 2023 Mar 6.

Abstract

The cortisol awakening response (CAR) is often assessed in the saliva and considered to be representative of serum cortisol. However, free cortisol is rapidly converted into cortisone as it passes from the serum into the saliva. Because of this enzymatic conversion, the salivary cortisone awakening response (EAR) may be more closely related to serum cortisol dynamics than the salivary CAR. Therefore, the purpose of this study was to measure the EAR and CAR in saliva and compare it to the serum CAR.

Methods: Male participants (n = 12) had an intravenous catheter placed for serial serum sampling and completed two overnight laboratory sessions, wherein participants slept in the laboratory and saliva and serum samples were collected every 15 min after volitional awakening the following morning. Serum was assayed for total cortisol and saliva for cortisol and cortisone. The CAR and EAR was assessed in saliva and the CAR in serum via mixed-effects growth models and common awakening response indices (area under the curve [AUC] relative to the ground [AUCG] and relative to the increase [AUCI], and change scores [Δ]).

Results: There was a distinct rise in salivary cortisone following awakening demonstrating the presence of a discernable EAR (βQuadratic = -41.18, [95%CI = -68.90 to -13.46], p < 0.004, Conditional R2 = 0.641). Two EAR indices (AUCG: p < 0.001 and AUCI: p = 0.030) were associated with the corresponding serum CAR indices.

Conclusion: We demonstrate for the first time a distinct cortisone awakening response. The results suggest the EAR may be more closely related to serum cortisol dynamics during the post-awakening period, and thus, may be a biomarker of interest in addition to the CAR for assessing hypothalamic-pituitary-adrenal axis functioning.

Keywords: Biomarker; Salivary.

MeSH terms

  • Circadian Rhythm / physiology
  • Cortisone*
  • Humans
  • Hydrocortisone*
  • Hypothalamo-Hypophyseal System
  • Male
  • Pituitary-Adrenal System
  • Saliva
  • Wakefulness / physiology

Substances

  • Hydrocortisone
  • Cortisone