Awakening not associated with an increased rate of cortisol secretion

Abstract

Cortisol is released upon activation of the hypothalamic-pituitary-adrenal axis, varies across the day, possesses an underlying diurnal rhythm and is responsive to stressors. The endogenous circadian peak of cortisol occurs in the morning, and increases in cortisol observed post-awakening have been named the cortisol awakening response (CAR) based on the belief that the act of waking up stimulates cortisol secretion. However, objective evidence that awakening induces cortisol secretion is limited. We used a mixed effects model with a linear spline fitted to the data to examine tissue-free cortisol measurements obtained from 201 healthy volunteers by automated ambulatory microdialysis before and after awakening in their home environments. We also examined rate of change of cortisol depending on sleep duration and relative timing. We found no evidence for a change in the rate of cortisol increase in the hour after waking when compared with the hour prior to waking. We instead observed substantial interindividual variability in the absolute concentration and rate of change of cortisol levels, and differences in dynamics that may be attributable to duration and relative timing of sleep. Based on these results, we strongly suggest caution is needed when interpreting cortisol measurements solely obtained in the hour after waking.

Keywords: circadian rhythm; cortisol; cortisol awakening response; human; microdialysis; sleep.

Figure 1.

Overnight tissue-free cortisol profiles in n = 201 healthy volunteers aligned by wake time. The rolling median (solid black) and quartile range (dashed black) lines (5th, 25th, 75th and 95th, bottom to top) are shown against the background of individual participant data (blue lines). Vertical line represents time of waking; shaded area represents 1 hr pre- and post-waking time. RW = rolling window.

Figure 2.

Cortisol values and cortisol rate of change in different sleep conditions. (A) Rolling median values for short (n = 51, solid blue) and long (n = 51, solid green) sleepers and (B) in aligned (n = 135, solid black) and misaligned (n = 64, solid red) sleepers. Rate of change of cortisol [nmol/( L. min)] in relation to wake time for short and long sleep (C) and misaligned versus aligned sleep (D) conditions. The 25th–75th centiles are shown with dotted lines and in hatched areas. RW = rolling window.