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Free Cortisol Levels after Awakening: A Reliable Biological Marker for the Assessment of Adrenocortical Activity
Abstract
In three independent studies, free cortisol levels after morning awakening were repeatedly measured in children, adults and elderly subjects (total n=152). Cortisol was assessed by sampling saliva at 10 or 15 minute intervals for 30-60 minutes, beginning at the time of awakening for two days (Study 1 and 2) or one (Study 3) day, respectively. In all three studies, free cortisol levels increased by 50-75% within the first 30 minutes after awakening in both sexes on all days. Premenopausal women consistently showed a stronger increase with a delayed peak after awakening compared to men on all days. In Study 2, there was a tendency for lower early morning free cortisol levels for women taking oral contraceptives (p=.10). Stability of the area under the curve (AUC) of the early morning free cortisol levels over the three (Study 1 and 2) or two (Study 3) days ranged between r=.39 and r=.67 (p<.001). Neither age, weight, nor smoking showed an effect on baseline or peak cortisol levels. Sleep duration, time of awakening and alcohol consumption also appeared to be unrelated to early morning free cortisol levels. From these data we conclude that in contrast to single assessments at fixed times, early morning cortisol levels can be a reliable biological marker for the individual's adrenocortical activity when measured repeatedly with strict reference to the time of awakening.
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In the citing paper
“the cortisol awakening response (CAR) – the pronounced (on average, 50–60%) increase in cortisol level that peaks approximately 30 to 40 min after waking (Pruessner et al. 1997).”
From The cortisol awakening response predicts major depression: predictive stability over a 4-year follow-up and effect of depression history (2013) · cites this paper as Pruessner et al. 1997
In the citing paper
“First, due to concerns about feasibility with 17-year-olds and participant burden, only two samples were collected to define the CAR (0 and 40 min after waking), rather than the original approach, which relied on samples taken every 10–15 min for 1 h after waking (Pruessner et al. 1997).”
From The cortisol awakening response predicts major depression: predictive stability over a 4-year follow-up and effect of depression history (2013) · cites this paper as Pruessner et al. 1997
In the citing paper
“The cortisol awakening response is a reliable marker of HPA axis activity which has been found to be increased by work stressors (Pruessner et al. 1997; Kunz-Ebrecht et al. 2004) and in individuals at high risk of depression (Mannie et al. 2007).”
From Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers (2015) · cites this paper as Pruessner et al. 1997
In the citing paper
“The cortisol awakening response is a reliable marker of HPA axis activity which has been found to be increased by work stressors (Pruessner et al. 1997; Kunz-Ebrecht et al. 2004) and in individuals at high risk of depression (Mannie et al. 2007).”
From Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers (2015) · cites this paper as Pruessner et al. 1997
In the citing paper
“Cortisol levels rise steeply immediately after awakening in the morning and peak approximately 30-45 minutes thereafter; from there, they slowly decrease throughout the day.”
From Psychosocial functioning and the cortisol awakening response: meta-analysis, P-curve analysis, and evaluation of the evidential value in existing studies (2017) · cites this paper as Pruessner, 1997
In the citing paper
“Cortisol diurnal rhythms vary according to individual sleep-wake schedules, being high upon waking, increasing to peak levels approximately 30-40 minutes after waking, and declining to a nadir around bedtime (Kirschbaum and Helhammer, 2000; Pruessner et al., 1997; Wilhelm et al., 2007).”
From Prospective prediction of major depressive disorder from cortisol awakening responses in adolescence (2010) · cites this paper as Pruessner et al., 1997
In the citing paper
“It is important to note that this study was originally designed to examine multiple elements of the cortisol diurnal rhythm across the day, in addition to the CAR. As a result, in order to reduce participant burden, the protocol for the CAR is less intensive, and thus less precise, than the original CAR protocol, in which cortisol levels were obtained every 10 to 15 minutes after awakening (Pruess”
From Prospective prediction of major depressive disorder from cortisol awakening responses in adolescence (2010) · cites this paper as Pruessner et al., 1997
In the citing paper
“awakenings and sleep offset are accompanied by cortisol stimulation”
From Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity (2010) · cites this paper as [39]
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Metadata
- Authors
- Pruessner, J. C., Wolf, O. T., Hellhammer, D. H., Buske-Kirschbaum, A., von Auer, K., Jobst, S., Kaspers, F., & Kirschbaum, C.
- Affiliations
- Universität Trier (DE)
- Corresponding author
- Kirschbaum, C.
- Venue
- Life Sciences
- Publisher
- Elsevier BV
- Published
- 1997-11
- Volume
- 61
- Issue
- 26
- Pages
- 2539-2549
- ISSN
- 0024-3205 (ISSN-L)
- OpenAlex
- W2057881388
- Cited by
- 1,450
- References
- 22
- Citations by year
- 2026: 31 · 2025: 37 · 2024: 42 · 2023: 50 · 2022: 56 · 2021: 71 · 2020: 91 · 2019: 67 · 2018: 63 · 2017: 69 · 2016: 93 · 2015: 73 · 2014: 92 · 2013: 80 · 2012: 72
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Life Sciences (publishedVersion)
- PubMed (publishedVersion)
- KOPS (University of Konstanz) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- free cortisol, early morning awakening, adrenocortical function, salivary cortisol, biomarkers, sex differences, premenopausal women, oral contraceptives, diurnal cortisol rhythm, measurement reliability
- MeSH terms
- Adrenal Cortex, Adult, Aged, Aging, Child, Circadian Rhythm, Contraceptives, Oral, Female, Humans, Hydrocortisone, Kinetics, Male, Saliva, Sleep, Smoking, Wakefulness, Biomarkers, Premenopause
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