Skip to main content
Intended for healthcare professionals
Restricted access
Research article
First published October 2002

Stress Hormones: How Do They Measure Up?

Abstract

Stress as a stimulus is integral to dynamic homeostatic functioning. However, evidence of its potentially deleterious effects on health is mounting. The impetus to understand the mechanisms that underlie stress-related negative health outcomes and prevent the development of stress-related disorders has never been greater. Symptom severity and subjective levels of stress, although frequently assessed in studies of stress in nursing research, may not provide adequate data to fully understand the pervasive effects of chronic or overwhelming stress associated with stress disorders. The measurement of stress hormones such as cortisol can help identify bodily changes that are stressor specific, people at risk for development of stress-related disorders, and the efficacy of interventions aimed at stress reduction. Cortisol, as the peripheral output of one of the major stress response systems, possesses several properties that make its measurement highly useful for investigations of stress. This article discusses some of the biological mechanisms involved in the stress response, why cortisol is commonly measured, and issues and approaches in cortisol measurement.

Get full access to this article

View all access and purchase options for this article.

References

Altemus M, Redwine L, Leong YM, Yoshikawa T, Yehuda R, Detera-Wadleigh S, Murphy DL. 1997. Reduced sensitivity to glucocorticoid feedback and reduced glucocorticoid receptor m RNA expression in the luteal phase of the menstrual cycle. Neuropsychopharmacology 17(2):100-109.
Bandelow B, Wedekind D, Pauls J, Broocks A, Hajak G, Rüther E. 2000. Salivary cortisol in panic attacks. Am J Psychiatry 157(3):454-456.
Baum A, Grunberg N. 1997. Measurement of stress hormones. In: Cohen S, Kessler RC, Gordon LU, editors. Measuring stress: A guide for health and social scientists. New York: Oxford University Press. p 175-192.
Berk RA . 2000. Does humor in course tests reduce anxiety and improve performance? Coll Teaching 48(4):151-164.
Biondi M, Picardi A. 1999. Psychological stress and neuroendocrine function in humans: The last two decades of research. Psychother Psychosom 68(3):114-151.
Bjorntrop P, Rosmond R. 2000. Obesity and cortisol. Nutrition 16(10):924-936.
Blood GW, Blood IM, Bennett S, Simpson KC, Susman EJ. 1994. Subjective anxiety measurements and cortisol responses in adults who stutter. J Speech Hearing Res 37(4):760-768.
Boyer P . 2000. Do anxiety and depression have a common pathophysiological mechanism? Acta Psychiatr Scand 102(S406):24-29.
Breier A . 1989. Experimental approaches to human stress research: assessment of neurobiological mechanisms of stress in volunteers and psychiatric patients. Biol Psychiatry 26:438-462.
Castro M, Elias PCL, Quidute ARP, Halah FPB, Moreira AC. 1999. Out-patient screening for Cushing’s syndrome: the sensitivity of the combination of circadian rhythm and overnight dexamethasone suppression salivary cortisol tests. J Clin Endocrinol Metab 84(3):878-882.
Caufriez A, Moreno-Reyes R, Leproult R, Vertongen F, Van Cauter E, Copinschi G. 2002. Immediate effects of an 8-h advance shift of the rest-activity cycle on 24-h profiles of cortisol. Am J Physiol Endocrinol Metab 282(5):E1147-E1153.
Cleare AJ, Heap E, Malhi GS, Wessely S. 1999. Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial. Lancet 353(9151):455-458.
Cleare AJ, Miell J, Heap E, Sookdeo S, Young L, Malhi GS, O’Keane V. 2001. Hypothalamo-pituitary-adrenal axis dysfunction in chronic fatigue syndrome, and the effects of lowdose hydrocortisone therapy. J Clin Endocrinol Metab 86(8):3545-3554.
Clearlock DM, Nuzzo NA. 2001. Effects of sustained moderate exercise on cholesterol, growth hormone and cortisol blood levels in three age groupswomen. Clin Lab Sci 14(2):108-114.
Cohen S, Kessler RC, Gordon LU. 1997. Strategies for measuring stress in studies of psychiatric and physical disorders. In: Cohen S, Kessler RC, Gordon LU, editors. Measuring stress: a guide for health and social scientists. New York: Oxford University Press. p 3-26.
DeBattista C, Posener JA, Kalehzan BM, Schatzberg AF. 2000. Acute antidepressant effects of intravenous hydrocortisone and CRH in depressed patients: Adouble-blind, placebo-controlled study. Am J Psychiatry 157(8):1334-1337.
Demitrack M, Dale J, Straus S, Laue L, Listwak S, Kruesi M, Chrousos G, Gold P. 1991. Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. J Clin Endocrinol Metab 73(6):1224-1234.
Epel ES, McEwen B, Seeman T, Matthews K, Castellazzo G, Brownell KD, Bell J, Ickovics JR. 2000. Stress and body shape: Stress-induced cortisol secretion is consistently greater among women with central fat. Psychosom Med 62(5):623-632.
Evans DL, Leserman J, Perkins DO, Stern RA, Murphy C. 1997. Severe life stress as a predictor of early disease progression in HIV infection. Am J Psychiatry 154(5):630-634.
Gibson EL, Checkley S, Papadopoulos A, Poon L, Daley S, Wardle J. 1999. Increased salivary cortisol reliably induced by a protein-rich midday meal. Psychosom Med 61(5):214-224.
Goh VH-H, Tong TY-Y, Lim C-L, Low EC-T, Lee LK-H. 2001. Effects of one night of sleep deprivation on hormone profiles and performance efficiency. Military Medicine 166(5):427-436.
Gregory T . 1999. Understanding depression in women. Patient Care 33(19):19-34.
Goenjian AK, Yehuda R, Pynoos RS, Steinberg AM, Tashjian M, Yang RK, Najarian LM, Fairbanks LA. 1996. Basal cortisol, dexamethasone suppression of cortisol, and MHPG in adolescents after the 1988 earthquake in Armenia. Am J Psychiatry 153:929-934.
Heckmann M, Wudy SA, Haack D, Pohlandt F. 1999. Reference range for serum cortisol in well preterm infants. Arch Dis Child Fetal Neonatal Ed 81(17):171-174.
Heim C, Ehlert U, Hellhammer DH. 2000. The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology 25:1-35.
Heim C, Newport DJ, Bonsall R, Miller AH, Nemeroff CB. 2001. Altered pituitary-adrenal axis responses to provocative challenge tests in adult survivors of childhood abuse. Am J Psychiatry 158(4):575-581.
Hennig J, Friebe J, Ryl I, Krämer B, Böttcher J, Netter P. 2000. Upright posture influences salivary cortisol. Psychoneuroendocrinology 25:69-83.
Hofman LF . 2001. Human saliva as a diagnostic specimen. J Nutrition 131(5):S1621-S1625.
Holsboer F, Barden N. 1996. Antidepressants and hypothalamicpituitaryadrenocortical regulation. Endocr Rev 17(20):187-205.
Hucklebridge F, Clow A, Rahman H, Evans P. 2000. The cortisol response to normal and nocturnal awakening. J Psychophysiol 14:24-28.
Huizenga NATM, Koper JW, de Lange P, Pols HAP, Stolk RP, Grobbee DE, de Jong FH, Lamberts SWJ. 1998. Interperson variability but intraperson stability of baseline plasma cortisol concentrations, and its relation to feedback sensitivity of the hypothalamo-pituitary-adrenal axis to a low dose of dexamethasone in elderly individuals. J Clin Endocrinol Metab 83(1):47-54.
Jett PL, Samuels MH, McDaniel PA, Benda GI, LaFranchi SH, Reynolds JW, Hanna CE. 1997. Variability of plasma cortisol levels in extremely low birth weight infants. J Clin Endocrinol Metab 82(9):2921-2925.
Keenan PA, Jacobson MW, Soleymani RM, Mayes MD, Stress ME, Yaldoo DT. 1996. The effect on memory of chronic prednisone treatment in patients with systemic disease. Neurology 47(6):1396-1402.
King JA, Rosal MC, Ma Y, Reed G, Kelly T-A, Stanek EJI, Ockene IS. 2000. Sequence and seasonal effects of salivary cortisol. Behav Med 26(2):67-74.
Kirschbaum C, Hellhammer DH. 2000. Salivary cortisol. Encyc Stress 3:379-383.
Kirschbaum C, Kudielka BM, Gaab J, Schommer NC, Hellhammer DH. 1999. Impact of gender, menstrual cycles, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis. Psychosomatic Med 61:154-162.
Kirschbaum C, Platte P, Pirke K, Hellhammer DH. 1996. Adrenocortical activation falling stressful exercise: further evidence for attenuated free cortisol responses in women using oral contraceptives. Stress Med 12:137-143.
Knutsson U, Dahlgren J, Marcus C, Rosberg S, Bronnegard M, Stierna P, Albertsson-Wikland K. 1997. Circadian cortisol rhythms in healthy boys and girls: relationship with age, growth, body composition, and pubertal development. J Clin Endocrinol Metab 82(2):536-540.
Kudielka BM, Schmidt-Reinwald AK, Hellhammer DH, Kirschbaum C. 1999. Psychological and endocrine responses to psychosocial stress and dexamethasone/ corticotropinreleasing hormone in healthy postmenopausal women and young controls: the impact of age and a two-week estradiol treatment. Neuroendocrinology 70(6):422-430.
Leproult R, Colecchia EF, L’Hermite-Baleriaux M, Van Cauter E. 2001. Transition from dim to bright light in the morning induces an immediate elevation of cortisol levels. J Clin Endocrinol Metab 86(1):151-157.
Leserman J, Petitto JM, Golden RN, Gaynes BN, Gu H, Perkins DO, Silva SG, Folds JD, Evans DL. 2000. Impact of stressful life events, depression, social support, coping, and cortisol on progression to AIDS. Am J Psychiatry 157(8):1221-1228.
Lupien SJ, deLeon M, De Santi S, Convit A, Tarshish C, Nair N, Thakur M, McEwen B, Hauger R, Meaney MJ. 1998. Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nat Neurosci 1:69-73.
Maniga JN, Golinsky S. 2001. Remarkable insights into health and disease are offered through analysis of saliva. Total Health 23(2):24-25.
Marti O, Garcia A, Velles A, Harbuz MS, Amario A. 2001. Evidence that a single exposure to adverse stimuli triggers longlasting effects in the hypothalamus-pituitary-adrenal access that consolidate with time. Eur J Neurosci 13:129-136.
McEwen BS . 1999. Stress and hippocampal plasticity. Ann Rev Neurosci 22(1):105-122.
Meaney MJ, Aitken DH, van Berkel C, Bhatnagar S, Sapolsky RM. 1988. Effect of neonatal handling of age-related impairments associated with the hippocampus. Science 239:766-768.
Mokrani MC, Duval F, Crocq MA, Bailey P, Macher JP. 1997. HPA axis dysfunction in depression: correlation with monoamine system abnormalities. Psychoneuroendocrinology 22:S63-S68.
Neeck G, Federlin K, Graef V, Rusch D, Schmidt KL. 1992. Adrenal secretion of cortisol in patients with rheumatoid arthritis. J Rheumatol 17:24-29.
Nelson JC, Davis JM. 1997. DST studies in psychotic depression: a meta-analysis. Am J Psychiatry 154(11):1497-1503.
Nicolson N, Storms C, Ponds R, Sulon J. 1997. Salivary cortisol levels and stress reactivity in human aging. J Gerontol 52A(2):M68-M75.
Oshima A, Yamashita S, Owashi T, Murata T, Tadokoro C, Miyaoka H, Kamijima K, Higuchi T. 2000. The differential ACTH responses to combined dexamethasone/CRH administrationin major depressive and dysthymic disorders. J Psychiatric-Res 34:325-328.
Osran H, Reist C, Chen C, Lifrak E, Chicz-DeMet A, Parker L. 1993. Adrenal androgens and cortisol in major depression. Am J Psychiatry 150(5):806-951.
Pacak K . 2000. Stressor-specific activation of the hypothalamicpituitaryadrenocortical axis. Physiol Res 49(Suppl 1):S11-S17.
Painter PC, Cope JY, Smith JL. 2001. Reference information for the clinical laboratory. In: Burtis CA, Ashwood ER, editors. Tietz fundamentals of clinical chemistry. 5th ed. Philadelphia: Saunders. p 955-1028.
Pajer K, Gardner W, Rubin RT, Perel J, Neal S. 2001. Decreased cortisol levels in adolescent girls with conduct disorder. Arch Gen Psychiatry 58(3):297-302.
Poland R, Rubin R, Lane L, Hart P, Lesser I. 1987. Serum dexamethasone concentration and hypothalamic-pituitary-adrenal cortical activity as determinants of the dexamethasone suppression test response. Arch Gen Psychiatry 44:790-795.
Reynolds RM, Bendall HE, Whorwood CB, Wood PJ, Walker BR, Phillips DIW. 1998. Reproducibility of the lowdose dexamethasone suppression test: comparison between direct plasma and salivary cortisol assays. Clin Endocrinol 49:307-310.
Roelfsema F, von der Berg G, Frolich M, Veldhuis JD, von Eijk A, Buurman MM, Etman BH. 1993. Sex-dependent alteration in cortisol response to endogenous adrenocorticotropin. J Clin Endocrinol Metab 77:234-240.
Samuels SC, Furlan PM, Boyce A, Katz IR. 1997. Salivary cortisol and daily events in nursing home residents. Am J Geriatric Psychiatry 5(2):172-176.
Sapolsky RM . 2000a. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 57(10):925-935.
Sapolsky RM . 2000b. Why zebras don’t get ulcers: an updated guided to stress, stress-related diseases, and coping. New York: W. H. Freeman.
Sapolsky RM, Armanini M, Packan D, Tombaugh G. 1987. Stress and glucocorticoids in aging. Endocrinol Metab Clin North Am 16:965-980.
Scheer FAJL, Buijs RM. 1999. Light affects morning salivary cortisol in humans. J Clin Endocrinol Metab 84(9):3395-3398.
Schimmer BP, Parker KL. 1996. Adrenocorticotropic hormone; adrenocortical steroids and their analogues; inhibitors of the synthesis and actions of adrenocortical hormones. In: Hardman JG, Limberg LE, Molinoff PB, Ruddon RW, Gilman AG, editors. Goodman & Gilman’s: the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill. p 1459-1485.
Shimada M, Takahashi K, Ohkawa, Segawa M, Higurashi M. 1995. Determination of salivary cortisol by ELISA and its application to the assessment of the circadian rhythm in children. Hormone Res 44:213-217.
Smyth JM, Ockenfels MC, Gorin AA, Catley D, Porter LS, Kirschbaum C, Hellhammer DH, Stone AA. 1997. Individual differences in the diurnal cycle of cortisol. Psychoneuroendocrinology 22(2):89-105.
Southwick SM, Yehuda R, Wang S. 1998. Neuroendocrine alterations in posttraumatic stress disorder. Psychiatric Annals 28(8):436-445.
Starkman MN, Gebarski SS, Berent S, Schteingart DE. 1992. Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing’s syndrome. Biol Psychiatry 32(9):756-765.
Vanderhaeghe L . 2001. Stress, aging and cortisol. Total Health 23(1):34-35.
Vanman EJ, Dawson ME, Brennan PA. 1998. Affective reactions in the blink of an eye: individual differences in subjective experience and physiological responses to emotional stimuli. Pers Soc Psychol Bull 24(9):994-1005.
Weinstein DD, Diforio D, Schiffman J, Walker E, Bonsall R. 1999. Minor physical anomalies, dermatoglyphic asymmetries, and cortisol levels in adolescents with schizotypal personality disorder. Am J Psychiatry 156(4):617-623.
Wilson DD . 1999. Nurse’s guide to understanding laboratory and diagnostic tests. Philadelphia: Lippincott.
Yanovski JA, Yanovski SZ, Gold PW, Chrousos GP. 1993. Differences in the hypothalamic-pituitary-adrenal axis of black and white women. J Clin Endocrinol Metab 77:536-541.
Yehuda R, Lowy M, Southwick S, Shaffer D, Giller E, Jr. 1991. Lymphocyte glucocorticoid receptor number in posttraumatic stress disorder. Am J Psychiatry 148(4):499-504.
Yehuda R, Southwick S, Krystal J, Bremner D, Charney D, Mason J. 1993. Enhanced suppression of cortisol following dexamethasone administration in posttraumatic stress disorder. Am J Psychiatry 150(1):83-86.
Young EA, Carlson NE, Brown MB. 2001. Twenty-four-hour ACTH and cortisol pulsatility in depressed women. Neuropsychopharmacology 25(2):267-276.
Zobel AW, Yassouridis A, Frieboes R-M, Holsboer F. 1999. Prediction of medium-term outcome by cortisol response to the combined dexamethasone-CRH test in patients with remitted depression. Am J Psychiatry 156(6):949-951.