Assessing Stress

// Corey Schuler, MS, DC, LN, CNS


The hypothalamic-pituitary-adrenal (HPA) axis is a highly adaptive system and measuring it can be difficult. A biochemical and a clinical tool combined may be more useful than just one or the other. The cortisol-awakening response (CAR) is a marker of circadian rhythm as well as HPA axis function. It is suspected that a sudden rise in cortisol helps to mobilize energy in the transition from sleep to wakefulness.1 Upon wakening, cortisol production and measurement in saliva peaks within the first 30-45 minutes.2 In 15-25% of individuals, a rise in cortisol is not observed.3 However, it should be noted that one study suggested that absence of CAR may be due to sampling error as instructions are prone to non-compliance for collection of saliva in the early morning.4 However, that is not a complete explanation for the lack of morning cortisol peaks.5 6 7Being a “morning person” rather than a “night owl” may contribute to variances in CAR.8 9 So too can situational factors add variance and serial values may be helpful in ruling out these variables.10 11 One may conceive that smoking, drinking coffee, menstrual cycle phase, oral contraceptive use, and sleep length may be major contributing factors to CAR, but they are of minor relative consequence.12 13 14 15 Yet, sudden changes in sleep-wake schedules do influence the timing of the cortisol rise.16 Sleep restriction as seen by the use of alarms can reduce cortisol secretion at awakening. CAR occurs in dark or light and whether the patient awakes and remains lying down or immediately rises. However, CAR is larger if patients are exposed to bright light. Exposure of 800 Lux is sufficient, which is approximately the same exposure as a partly cloudy day or a bright kitchen. An overly robust cortisol-awakening response may be indicative of a condition that requires further evaluation.17 18 19 20 21 22

The cortisol-awakening response (CAR) is a marker of circadian rhythm as well as HPA axis function.

Limiting the assessment of stress to cortisol may only weakly guide interventions. Understanding other lifestyle factors further contributes to understanding patients’ responses. While not suitable for most clinical environments, a validated testing procedure provides helpful information about what does and does not activate the HPA and to what magnitude. This procedure is the Trier Social Stress Test (TSST).23 TSST includes a mock job interview and performing mental arithmetic in front of an audience who has been trained to not provide positive nor negative feedback. This provocative test is not a test of maximal stress response, but rather of sub-maximal novel stressors. While not predictive of any particular condition, TSST provides valuable information about determinants of HPA activity and reactivity.

Despite being incomplete of the representative literature on the subject, the following factors affect the HPA according to TSST research.

  • Smoking 24
  • Caffeine 25
  • Alcohol 26
  • Excess Food 27 28
  • High glucose load 29
  • Socially dominant men are affected more so than subordinate men 30

Factors that attenuate the HPA response include

  • Social support with the greatest effect in men via oxytocin31
  • Caffeine 25
  • Brief group-based cognitive-behavioral management 32 33
  • Relaxing music34
  • Progressive muscle relaxation35

Of significant interest is that larger HPA responses have been reported in men independent of age differences. The hypothesis stands that female sex hormones may attenuate the HPA axis response and some hormone-related changes in women may be due to varying HPA axis responses. Women in the luteal phase of their menstrual cycle reported similar responses to men while those using oral contraceptives or in the follicular phase did not.

The complexity of the hypothalamic-pituitary-adrenal axis with considerable environmental, behavioral, physiological, and psychological is an important system for the integrative practitioner to master clinically. It is however, an art, with no overly simple assessments providing complete answers. Assessment and support of the HPA axis requires recognition of each of these important factors.

HPA Axis Optimization Program

1.Pruessner JC, Wolf OT, Hellhammer DH, et al. Free cortisol levels after awakening: A reliable biological marker for the assessment of adrenocortical activity. Life Sci 1997;61:2539–2549
2.Wust S, Wolf J, Hellhammer DH, Federenko I, Schommer N, Kirschbaum C. The cortisol awakening response— normal values and confounds. Noise Health 2000; 2:79–88
3.. Dockray S, Bhattacharyya MR, Molloy GJ, Steptoe A. The cortisol awakening response in relation to objective and subjective measures of waking in the morning. Psychoneuroendocrinology 2008; 33:77–82.
4. Kudielka BM, Broderick JE, Kirschbaum C. Compliance with saliva sampling protocols: Electronic monitoring reveals invalid cortisol daytime profiles in noncompliant subjects. Psychosom Med 2003; 65:313–319.
5.Buchanan TW, Kern S, Allen JS, Tranel D, Kirschbaum C. Circadian regulation of cortisol after hippocampal damage in humans. Biol Psychiatry 2004; 56:651–656.
6.Bruehl H, Wolf OT, Convit A. A blunted cortisol awakening response and hippocampal atrophy in type 2 diabetes mellitus. Psychoneuroendocrinology 2009;34: 815–821.
7.Wolf OT, Fujiwara E, Luwinski G, Kirschbaum C, Markowitsch HJ. No morning cortisol response in patients with severe global amnesia. Psychoneuroendocrinology 2005; 30:101–105.
8.Kudielka BM, Federenko IS, Hellhammer DH, Wust S. Morningness and eveningness: The free cortisol rise after awakening in ‘early birds’ and ‘night owls’. Biol Psychol 2006; 72:141–146.
9.Kudielka BM, Bellingrath S, Hellhammer DH. Further support for higher salivary cortisol levels in ‘morning’ compared to ‘evening’ persons. J Psychosom Res 2007; 62:595–596.
10.Hellhammer J, Fries E, Schweisthal OW, et al. Several daily measurements are necessary to reliably assess the cortisol rise after awakening: State- and trait components. Psychoneuroendocrinology 2007;32:80–86.
11.Stalder T, Hucklebridge F, Evans P, Clow A. Use of a single case study design to examine state variation in the cortisol awakening response: Relationship with time of awakening. Psychoneuroendocrinology 2008; 34:607–614.
12.Clow A, Thorn L, Evans P, Hucklebridge F. The awakening cortisol response: Methodological issues and significance. Stress 2004; 7:29–37.
13.Steptoe A, Ussher M. Smoking, cortisol and nicotine. Int J Psychophysiol 2006; 59:228–235.
14.Badrick E, Kirschbaum C, Kumari M. The relationship between smoking status and cortisol secretion. J Clin Endocrinol Metab 2007; 92:819–824
15.Harris A, Ursin H, Murison R, Eriksen HR. Coffee, stress and cortisol in nursing staff. Psychoneuroendocrinology 2007; 32: 322–330.
16.Davidson JR, Moldofsky H, Lue FA. Growth hormone and cortisol secretion in relation to sleep and wakefulness. J Psychiatry Neurosci 1991; 16:96–102.
17. Bhattacharyya MR, Molloy GJ, Steptoe A. Depression is associated with flatter cortisol rhythms in patients with coronary artery disease. J Psychosom Res 2008; 65:107–113.
18. Edwards S, Hucklebridge F, Clow A, Evans P. Components of the diurnal cortisol cycle in relation to upper respiratory symptoms and perceived stress. Psychosom Med 2003; 65:320–327
19. Wallerius S, Rosmond R, Ljung T, Holm G, Bjorntorp P. Rise in morning saliva cortisol is associated with abdominal obesity in men: A preliminary report. J Endocrinol Invest 2003; 26:616–619.
20. Steptoe A, Kunz-Ebrecht SR, Brydon L, Wardle J. Central adiposity and cortisol responses to waking in middle-aged men and women. Int J Obes Relat Metab Disord 2004; 28:1168–1173.
21. Steptoe A, Wright CE, O’Donnell K, Brydon L, Wardle J. Parental adiposity and cortisol awakening responses in young men and women. Psychoneuroendocrinology 2006; 31:1117–1126.
22. Therrien F, Drapeau V, Lalonde J, et al. Awakening cortisol response in lean, obese, and reduced obese individuals: Effect of gender and fat distribution. Obesity (Silver Spring) 2007; 15:377–385.
23. Kirschbaum C, Pirke KM, Hellhammer DH. The ‘Trier social stress test’—a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 1993; 28: 76–81.
24. Kirschbaum C, Strasburger CJ, Langkrar J. Attenuated cortisol response to psychological stress but not to CRH or ergometry in young habitual smokers. Pharmacol Biochem Behav 1993;44:527–531
25.Lovallo WR, Farag NH, Vincent AS, Thomas TL, Wilson MF. Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women. Pharmacol Biochem Behav 2006; 83:441–447.
26. Lovallo WR, Dickensheets SL, Myers DA, Thomas TL, Nixon SJ. Blunted stress cortisol response in abstinent alcoholic and polysubstance-abusing men. Alcohol Clin Exp Res 2000;24:651–658.
27. Kirschbaum C, Gonzalez Bono E, Rohleder N, et al. Effects of fasting and glucose load on free cortisol responses to stress and nicotine. J Clin Endocrinol Metab 1997;82:1101–1105.
28. Rohleder N, Kirschbaum C. 2007. Effects of nutrition on neuroendocrine stress responses. Curr Opin Clin Nutr Metab Care 10:504–510.
29. Gonzalez-Bono E, Rohleder N, Hellhammer DH, Salvador A, Kirschbaum C. Glucose but not protein or fat load amplifies the cortisol response to psychosocial stress. Horm Behav 2002;41:328–333.
30. Hellhammer DH, Buchtal J, Gutberlet I, Kirschbaum C. Social hierarchy and adrenocortical stress reactivity in men. Psychoneuroendocrinology 1997; 22:643–650.
31. Kirschbaum C, Klauer T, Filipp SH, Hellhammer DH. Sex specific effects of social support on cortisol and subjective responses to acute psychological stress. Psychosom Med 1995; 57:23–31.
32. Gaab J, Blattler N, Menzi T, et al. Randomized controlled evaluation of the effects of cognitive-behavioral stress management on cortisol responses to acute stress in healthy subjects. Psychoneuroendocrinology 2003;28:767–779.
33. Hammerfald K, Eberle C, Grau M, et al. Persistent effects of cognitive-behavioral stress management on cortisol responses to acute stress in healthy subjects–a randomized controlled trial. Psychoneuroendocrinology 2006; 31:333–339
34. Khalfa S, Bella SD, Roy M, Peretz I, Lupien SJ. Effects of relaxing music on salivary cortisol level after psychological stress. Ann N Y Acad Sci 2003; 999:374–376.
35.Vocks S, Ockenfels M, Jurgensen R, Mussgay L, Ruddel H. Blood pressure reactivity can be reduced by a cognitive behavioral stress management program. Int J Behav Med 2004; 11:63–70.


Integrative Blog RSSBlog Feed



†† For homeopathic products: these indications are based solely on traditional homeopathic use. They have not been evaluated by the Food & Drug Administration.
* For dietary supplements: this statement has not been evaluated by the Food & Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

© Integrative Therapeutics, LLC.