Why do we respond so differently? Reviewing determinants of human salivary cortisol responses to challenge

Kudielka, Brigitte M.; Hellhammer, D.H.; Wüst, Stefan

doi:10.1016/j.psyneuen.2008.10.004

Cited by 963Stress Responses and CortisolAdrenal Hormones and DisordersHeart Rate Variability and Autonomic Control

Why do we respond so differently? Reviewing determinants of human salivary cortisol responses to challenge

Kudielka, Brigitte M., Hellhammer, D.H., Wüst, Stefan·2009·Psychoneuroendocrinology

DOI 10.1016/j.psyneuen.2008.10.004

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Abstract

Stress and stress-related health impairments are major problems in human life and elucidating the biological pathways linking stress and disease is of substantial importance. However, the identification of mechanisms underlying a dysregulation of major components of the stress response system is, particularly in humans, a very challenging task. Salivary cortisol responses to diverse acute challenge paradigms show large intra- and interindividual variability. In order to uncover mechanisms mediating stress-related disorders and to potentially develop new therapeutic strategies, an extensive phenotyping of HPA axis stress responses is essential. Such a research agenda depends on substantial knowledge of moderating and intervening variables that affect cortisol responses to different stressors and stimuli. The aim of this report is, therefore, to provide a comprehensive summary of important determinants of, in particular, human salivary cortisol responses to different kinds of laboratory stimuli including acute psychosocial stress as well as pharmacological provocation procedures. This overview demonstrates the role of age and gender, endogenous and exogenous sex steroid levels, pregnancy, lactation and breast-feeding, smoking, coffee and alcohol consumption as well as dietary energy supply in salivary cortisol responses to acute stress. Furthermore, it briefly summarizes current knowledge of the role of genetic factors and methodological issues in terms of habituation to repeated psychosocial stress exposures and time of testing as well as psychological factors, that have been shown to be associated with salivary cortisol responses like early life experiences, social factors, psychological interventions, personality as well as acute subjective-psychological stress responses and finally states of chronic stress and psychopathology.

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Among studies using the TSST, there is some agreement that under stress, cortisol increases are greater in the luteal phase relative to other phases in women not taking oral contraceptives.
“In general, among the studies that used the TSST as a form of mental stress to activate the HPA axis, there seems to be some agreement that when under stress, cortisol increases are greater in the luteal phase relative to the other phases in women who are not taking OC (e.g., Kudielka et al., 2009; Rohleder et al., 2001; Rohleder et al., 2003; Schoof and Wolf, 2009).”
From The relationship between the menstrual cycle and cortisol secretion: Daily and stress-invoked cortisol patterns (2018) · cites this paper as Kudielka et al., 2009
In public speaking tasks, sex differences in HPA responsivity are inconsistent; when found, they indicate stronger responses in men, though women show increased cortisol response in the luteal phase.
“In public speaking tasks, sex differences in HPA responsivity show an inconsistent pattern; when effects are found, they indicate stronger responses in men, although women show increased cortisol response in the luteal phase of the menstrual cycle (Kajantie and Phillips, 2006; Kudielka and Kirshbaum, 2005; Kudielka et al., 2009)”
From The Adaptive Calibration Model of stress responsivity (2011) · cites this paper as Kudielka et al., 2009

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Acute Hormonal Responses to Heavy Resistance Exercise in Men and Women at Different Ages
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Untitled work
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“, free speech,mental arithmetic, experimental harassment) is the significantly larger salivary cortisol response in healthy adult men compared to women following short-term laboratory stress (Steptoe et al., 1996; Nicolson et al., 1997; Earle et al., 1999; Seeman et al., 2001; Lovallo et al., 2006).”
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The corticotrophin releasing hormone test in late pregnancy: lack of adrenocorticotrophin and cortisol response
SCHULTE, H. M., WEISNER, D., & ALLOLIO, B. (1990) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1990.tb00470.x · Cited by 199 · see citing works
Suppression of the HPA Axis Stress‐Response: Implications for Relapse
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Sex Differences in Endocrine and Psychological Responses to Psychosocial Stress in Healthy Elderly Subjects and the Impact of a 2-Week Dehydroepiandrosterone Treatment1
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Heritability of cortisol responses to human corticotropin-releasing hormone, ergometry, and psychological stress in humans.
Kirschbaum, C., Wüst, S., Faig, H. G., & Hellhammer, D. H. (1992) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.75.6.1464659 · Cited by 195 · see citing works
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Implications of estrogen‐dependent brain organization for gender differences in hypothalamo‐pituitary‐adrenal regulation
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The Heritability of Hypothalamus Pituitary Adrenal Axis Responses to Psychosocial Stress Is Context Dependent
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Childhood Attachment and Loss Experiences Affect Adult Cardiovascular and Cortisol Function
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Decreased Hypothalamic-Pituitary Adrenal Axis Sensitivity to Cortisol Feedback Inhibition in Human Aging
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‘Normal’ cigarette smoking increases free cortisol in habitual smokers
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Abnormal Cortisol Secretion and Responses to Corticotropin-Releasing Hormone in Women with Hypothalamic Amenorrhea*
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Diet-hormone interactions: Protein/carbohydrate ratio alters reciprocally the plasma levels of testosterone and cortisol and their respective binding globulins in man
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Short-term estradiol treatment enhances pituitary-adrenal axis and sympathetic responses to psychosocial stress in healthy young men
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Habituation of cortisol responses to repeated psychosocial stress—further characterization and impact of genetic factors
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Acute hormonal responses to heavy resistance exercise in younger and older men
Kraemer, W. J., H�kkinen, K., Newton, R. U., McCormick, M., Nindl, B. C., Volek, J. S., Gotshalk, L. A., Fleck, S. J., Campbell, W. W., Gordon, S. E., et al. (1998) · European Journal of Applied Physiology · doi:10.1007/s004210050323 · Cited by 167 · see citing works
HPA system regulation and adult attachment anxiety: individual differences in reactive and awakening cortisol
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Persistent effects of cognitive-behavioral stress management on cortisol responses to acute stress in healthy subjects—A randomized controlled trial
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Delayed response and lack of habituation in plasma interleukin-6 to acute mental stress in men
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Attenuated cortisol response to psychological stress but not to CRH or ergometry in young habitual smokers
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Lactation and Stress: Protective Effects of Breast-feeding in Humans
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Relationship between Plasma Profiles of Oxytocin and Adrenocorticotropic Hormone during Suckling or Breast Stimulation in Women
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Caffeine Stimulation of Cortisol Secretion Across the Waking Hours in Relation to Caffeine Intake Levels
Lovallo, W. R., Whitsett, T. L., al’Absi, M., Sung, B. H., Vincent, A. S., & Wilson, M. F. (2005) · Psychosomatic Medicine · doi:10.1097/01.psy.0000181270.20036.06 · Cited by 153 · cited 2× · see citing works
“Beside nicotine, it has been shown that caffeine intake can potentially activate important components of the pituitaryadrenocortical response in humans during resting states leading to increased plasma as well as salivary cortisol levels (Lovallo et al., 1996, 2005).”
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Cardiovascular responses to psychological and physiological stressors during the menstrual cycle.
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Effects of hot tea, coffee and water ingestion on physiological responses and mood: the role of caffeine, water and beverage type
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Localization of 11 beta-hydroxysteroid dehydrogenase type II in human epithelial tissues.
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Caffeine Effects on Cardiovascular and Neuroendocrine Responses to Acute Psychosocial Stress and Their Relationship to Level of Habitual Caffeine Consumption
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Psychiatric implications of altered limbic-hypothalamic-pituitary-adrenocortical activity
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Pharmacological and Nonpharmacological Factors Influencing Hypothalamic–Pituitary–Adrenocortical Axis Reactivity in Acutely Depressed Psychiatric In-patients, Measured by the Dex-CRH Test
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Suckling-Induced Attenuation of Plasma Cortisol Concentrations in Postpartum Lactating Women
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Birth weight is associated with salivary cortisol responses to psychosocial stress in adult life
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Effects of Fasting and Glucose Load on Free Cortisol Responses to Stress and Nicotine1
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Meal stimulation of cortisol secretion: A protein induced effect
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Effects of age and gender on pituitary-adrenocortical responsiveness in humans
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A MID-DAY SURGE IN CORTISOL LEVELS
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Psychological and Endocrine Responses to Psychosocial Stress and Dexamethasone/ Corticotropin-Releasing Hormone in Healthy Postmenopausal Women and Young Controls: The Impact of Age and a Two-Week Estradiol Treatment
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“, 2001), including salivary cortisol responses (Kudielka et al., 1999).”
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Adrenocortical function in old age: response to acute adrenocorticotropin stimulation.
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Spontaneous and Glucocorticoid-Inhibited Adrenocorticotropic Hormone and Cortisol Secretion are Similar in Healthy Young and Old Men*
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Middle-aged men show higher sensitivity of sleep to the arousing effects of corticotropin-releasing hormone than young men: clinical implications
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Ligand requirements of the human corticotropin-releasing factor-binding protein
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Circadian effects on the acute responses of salivary cortisol and IgA in well trained swimmers
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Simultaneous Measurement of Cortisol in Serum and Saliva After Different Forms of Cortisol Administration
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Effects of Aging on Adrenal Function in the Human: Responsiveness and Sensitivity of Adrenal Androgens and Cortisol to Adrenocorticotropin in Premenopausal and Postmenopausal Women
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Differential effects of harassment on cardiovascular and salivary cortisol stress reactivity and recovery in women and men
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A randomized controlled trial of high dose ascorbic acid for reduction of blood pressure, cortisol, and subjective responses to psychological stress
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Glucose but Not Protein or Fat Load Amplifies the Cortisol Response to Psychosocial Stress
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Variations in heritability of cortisol reactivity to stress as a function of early familial adversity among 19-month-old twins
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Effect of Ethanol on Hypothalamic–Pituitary–Adrenal System Response to Psychosocial Stress in Sons of Alcohol-Dependent Fathers
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Fetal Programming of the Hypothalamic-Pituitary-Adrenal (HPA) Axis: Low Birth Weight and Central HPA Regulation
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Responses of plasma adrenocortical steroids to low dose ACTH in normal subjects
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Effects of Fasting and Glucose Load on Free Cortisol Responses to Stress and Nicotine
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Cardiovascular Risk and Responsivity to Mental Stress: The Influence of Age, Gender and Risk Factors
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Acute hormone responses to heavy resistance lower and upper extremity exercise in young versus old men
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Caffeine Affects Cardiovascular and Neuroendocrine Activation at Work and Home
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Estrogen Supplementation Attenuates Glucocorticoid and Catecholamine Responses to Mental Stress in Perimenopausal Women
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Influence of short-term cycling on salivary cortisol levels
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Cortisol responses to psychological stress and correlations with personality traits
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Effect of chronic alcohol consumption on the activity of the hypothalamic-pituitary-adrenal axis and pituitary beta-endorphin as a function of alcohol intake, age, and gender.
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An assessment of hypothalamo-pituitary-adrenal axis functioning in non-depressed, early abstinent alcoholics
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Cortisol in burnout and vital exhaustion: an overview.
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Impact of oral contraceptive use on glucocorticoid sensitivity of pro-inflammatory cytokine production after psychosocial stress
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Pituitary and adrenal hormone responses to pharmacological, physical, and psychological stimulation in habitual smokers and nonsmokers
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Hypothalamic-Pituitary-Adrenocortical Responses to Psychological Stress and Caffeine in Men at High and Low Risk for Hypertension
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Long-term citalopram administration reduces responsiveness of HPA axis in patients with major depression: relationship with S-citalopram concentrations in plasma and cerebrospinal fluid (CSF) and clinical response
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Age and sex steroid-related changes in glucocorticoid sensitivity of pro-inflammatory cytokine production after psychosocial stress
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Sex Differences in Neonatal Stress Reactivity
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Circadian rhythm of cortisol confounds cortisol responses to exercise: implications for future research
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Postmenopausal Hormone Replacement
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Feedback from Meal-Related Peaks Determines Diurnal Changes in Cortisol Response to Exercise
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Cortisol and ACTH responses to psychosocial stress are modulated by corticosteroid binding globulin levels
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Cortisol and Growth Hormone Responses to Psychological Stress during the Menstrual Cycle
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Adrenocortical Responses to Repeated Parachute Jumping and Subsequent h-CRH Challenge in Inexperienced Healthy Subjects
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Endocrine and Immune Responses to Stress in Chronic Inflammatory Skin Disorders
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Attenuation of the hypothalamic–pituitary–adrenal axis responsivity to the Trier Social Stress Test by the benzodiazepine alprazolam
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Response of the HPA-axis to alcohol and stress as a function of alcohol dependence and family history of alcoholism
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The effect of natural habituation on coagulation responses to acute mental stress and recovery in men
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The Adaptive Calibration Model of stress responsivity
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Best practices for stress measurement: how to measure psychological stress in health research
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Trier Social Stress Test
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Cortisol and DHEA in development and psychopathology
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Trait mindfulness modulates neuroendocrine and affective responses to social evaluative threat
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Brief, daily meditation enhances attention, memory, mood, and emotional regulation in non-experienced meditators
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Effects of stress on decisions under uncertainty: A meta-analysis.
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Parent support is less effective in buffering cortisol stress reactivity for adolescents compared to children
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Cognitive Impairment in Major Depression: Association with Salivary Cortisol
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Personality and physiological reactions to acute psychological stress
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Estrogen and the prefrontal cortex: Towards a new understanding of estrogen's effects on executive functions in the menopause transition
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Oxytocin buffers cortisol responses to stress in individuals with impaired emotion regulation abilities
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Childhood Trauma Is Associated With Hypothalamic-Pituitary-Adrenal Axis Responsiveness in Irritable Bowel Syndrome
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The Presence of a Dog Attenuates Cortisol and Heart Rate in the Trier Social Stress Test Compared to Human Friends
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The Detection of Cortisol in Human Sweat
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Cortisol levels in former preterm children at school age are predicted by neonatal procedural pain-related stress
Brummelte, S., Chau, C. M. Y., Cepeda, I. L., Degenhardt, A., Weinberg, J., Synnes, A. R., & GRUNAU, R. E. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.09.018 · Cited by 187 · see citing works
Influence of Regular Physical Activity and Fitness on Stress Reactivity as Measured with the Trier Social Stress Test Protocol: A Systematic Review
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Variability in Human-Animal Interaction Research
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The cortisol awakening response – Applications and implications for sleep medicine
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Does stress alter everyday moral decision-making?
Starcke, K., Polzer, C., Wolf, O. T., & Brand, M. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2010.07.010 · Cited by 188 · see citing works
Nicotinic acetylcholine receptors and depression: a review of the preclinical and clinical literature
Philip, N. S., Carpenter, L. L., Tyrka, A. R., & Price, L. H. (2010) · Psychopharmacology · doi:10.1007/s00213-010-1932-6 · Cited by 185 · see citing works
The interaction between stress and chronic pain through the lens of threat learning
Timmers, I., Quaedflieg, C., Hsu, C. M., Heathcote, L., Rovnaghi, C., & Simons, L. (2019) · Neuroscience and Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.10.007 · Cited by 171 · see citing works
Interindividual differences and intraindividual variability in the cortisol awakening response: An examination of age and gender.
Almeida, D. M., Piazza, J. R., & Stawski, R. S. (2009) · Psychology and Aging · doi:10.1037/a0017910 · Cited by 179 · see citing works
Worse than sticks and stones? Bullying is associated with altered HPA axis functioning and poorer health
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Cardiovascular and cortisol reactivity and habituation to a virtual reality version of the Trier Social Stress Test: A pilot study
Jönsson, P., Wallergård, M., Österberg, K., Hansen, Å. M., Johansson, G. I., & Karlson, B. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2010.04.003 · Cited by 168 · see citing works
Decision making under objective risk conditions – a review of cognitive and emotional correlates, strategies, feedback processing, and external influences
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It feels real: physiological responses to a stressful virtual reality environment and its impact on working memory
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Children's and adults' salivary cortisol responses to an identical psychosocial laboratory stressor.
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Does the level of physical exercise affect physiological and psychological responses to psychosocial stress in women?
Klaperski, S., von Dawans, B., Heinrichs, M., & Fuchs, R. (2013) · Psychology of Sport and Exercise · doi:10.1016/j.psychsport.2012.11.003 · Cited by 150 · see citing works
A systematic review of the Trier Social Stress Test methodology: Issues in promoting study comparison and replicable research
Linares, N. F. N., Charron, V., Ouimet, A., Labelle, P., & Plamondon, H. (2020) · Neurobiology of Stress · doi:10.1016/j.ynstr.2020.100235 · Cited by 129 · see citing works
Fibromyalgia syndrome is associated with hypocortisolism
Riva, R., Mork, P. J., Westgaard, R. H., Rø, M., & Lundberg, U. (2010) · International Journal of Behavioral Medicine · doi:10.1007/s12529-010-9097-6 · Cited by 143 · see citing works
Summary cortisol reactivity indicators: Interrelations and meaning
Khoury, J. E., González, A., Levitan, R. D., Pruessner, J. C., Chopra, K. K., Basile, V. S., Masellis, M., Goodwill, A. M., & Atkinson, L. R. (2015) · Neurobiology of Stress · doi:10.1016/j.ynstr.2015.04.002 · Cited by 144 · see citing works
Evolutionary functions of early social modulation of hypothalamic-pituitary-adrenal axis development in humans
Flinn, M. V., Nepomnaschy, P. A., Muehlenbein, M. P., & Ponzi, D. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.01.005 · Cited by 139 · see citing works
Can architectural design alter the physiological reaction to psychosocial stress? A virtual TSST experiment
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Psychological and physiological stress in non-competitive and competitive esports settings: A systematic review
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HPA axis responses to psychological challenge linking stress and disease: What do we know on sources of intra- and interindividual variability?
Zänkert, S., Bellingrath, S., Wüst, S., & Kudielka, B. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.10.027 · Cited by 124 · see citing works
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Early life stress modulates amygdala‐prefrontal functional connectivity: Implications for oxytocin effects
Fan, Y., Herrera-Meléndez, A. L., Pestke, K., Feeser, M., Aust, S., Otte, C., Pruessner, J. C., Böker, H., Bajbouj, M., & Grimm, S. (2014) · Human Brain Mapping · doi:10.1002/hbm.22553 · Cited by 134 · see citing works
Heritability and genetic correlation of hair cortisol in vervet monkeys in low and higher stress environments
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Authors: Kudielka, B. M., Hellhammer, D. H., & Wüst, S.
Affiliations: Constructor University (DE)
Universität Trier (DE)
Central Institute of Mental Health (DE)
Corresponding author: Kudielka, Brigitte M.
ORCID: Kudielka, Brigitte M.
Hellhammer, D.H.
Wüst, Stefan
Venue: Psychoneuroendocrinology
Publisher: Elsevier BV
Published: 2009-01
Volume: 34
Issue: 1
Pages: 2-18
ISSN: 0306-4530 (ISSN-L)
DOI: 10.1016/j.psyneuen.2008.10.004
OpenAlex: W2057119719
Cited by: 963
References: 241
Citations by year: 2026: 38 · 2025: 38 · 2024: 42 · 2023: 36 · 2022: 50 · 2021: 56 · 2020: 70 · 2019: 61 · 2018: 62 · 2017: 61 · 2016: 67 · 2015: 62 · 2014: 61 · 2013: 62 · 2012: 60
FWCI: 3.24
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Psychoneuroendocrinology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
Keywords: salivary cortisol, hypothalamic-pituitary-adrenal axis, acute psychosocial stress, sex steroids, age and gender differences, pregnancy and lactation, smoking, energy intake, genetic factors, early life experience, personality, chronic stress, psychopathology
MeSH terms: Age Factors, Animals, Breast Feeding, Nonprescription Drugs, Female, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Lactation, Life Change Events, Male, Personality, Pregnancy, Saliva, Sex Characteristics, Stress, Physiological, Stress, Psychological

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Why do we respond so differently? Reviewing determinants of human salivary cortisol responses to challenge

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