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The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 6 1853-1859
Copyright © 1998 by The Endocrine Society


Original Studies

Stress-Related Cortisol Secretion in Men: Relationships with Abdominal Obesity and Endocrine, Metabolic and Hemodynamic Abnormalities1

Roland Rosmond, Mary F. Dallman and Per Björntorp

Department of Heart and Lung Diseases, Sahlgrenska University Hospital (R.R., P.B.), S-413 45 Göteborg, Sweden; and the Department of Physiology, University of California (M.F.D.), San Francisco, California 94143

Address all correspondence and requests for reprints to: Roland Rosmond, M.D., Department of Heart and Lung Diseases, Sahlgrenska University Hospital, S-413 45 Goteborg, Sweden.

Abdominal obesity has been suggested to be associated with perturbations of the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. In a population of 51-yr-old men (n = 284) salivary cortisol concentrations were determined on repeated (n = 7) occasions over a random working day, and perceived stress was reported in parallel. Cortisol values were then related to reported stress (stress-related cortisol). A standardized lunch was used as a physiological challenge. A low dose (0.5 mg) dexamethasone suppression test was also performed as well as determinations of testosterone and insulin-like growth factor I (IGF-I). Body mass index [weight (kilograms)/height (meters)2]; waist/hip circumference ratio (WHR); sagittal trunk recumbent diameter (D); fasting insulin; blood glucose; triglycerides; and total, low density (LDL), and high density (HDL) lipoprotein cholesterol were also determined.

Cortisol concentrations were highest in the morning, and lunch was followed by a peak (P = 0.044). Two types of diurnal cortisol curves were identified, one characterized by a high variability with high morning values, and another with low variability and low morning values. Both correlated strongly with suppression of salivary cortisol by dexamethasone (P < 0.001).

Stress-related cortisol secretion was associated with D (P = 0.051), low IGF-I (P = 0.006), and diastolic blood pressure (P = 0.078). When the type of diurnal cortisol curve was taken into consideration by statistical weighting, stress-related cortisol secretion in subjects with high variability showed associations with testosterone (P < 0.001), D, total and LDL cholesterol, diastolic blood pressure (P < 0.001), fasting insulin (P = 0.039), and glucose (P = 0.030) as well as, negatively, triglycerides (P < 0.001).

When weighted for a low variability of diurnal cortisol secretion, stress-related cortisol secretion showed strong negative relationships with IGF-I, testosterone, and HDL. Furthermore, strong, consistent relationships (all P < 0.001) were found with obesity factors (body mass index, WHR, and D), and with metabolic (insulin, glucose, triglycerides, and total and LDL cholesterol) as well as hemodynamic variables (systolic and diastolic blood pressure and heart rate).

These results clearly show interactions between diurnal cortisol secretion related to perceived stress and anthropometric, endocrine, metabolic, and hemodynamic variables. This seems to occur with apparently normal regulation of the HPA axis (high morning peaks and variability as well as dexamethasone suppression of cortisol), where other endocrine variables are not affected. With a low diurnal cortisol variation and blunted dexamethasone suppression, indicating abnormal regulation of the HPA axis, perceived stress-dependent cortisol values were strongly related to perturbations of other endocrine axes as well as abdominal obesity with metabolic and hemodynamic abnormalities. Perturbations of the regulation of the HPA axis such as those described in combination with low dexamethasone suppressibility are known to follow long term overactivation of the axis by factors such as environmental stress.




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Leptin Activation of Corticosterone Production in Hepatocytes May Contribute to the Reversal of Obesity and Hyperglycemia in Leptin-Deficient ob/ob Mice
Diabetes, June 1, 2003; 52(6): 1409 - 1416.
[Abstract] [Full Text] [PDF]


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Hum ReprodHome page
J.G. Dolfing, K.E. Tucker, C.M. Lem, J. Uittenbogaart, J.C. Verzijl, and D.H. Schweitzer
Low 11-deoxycortisol to cortisol conversion reflects extra-adrenal factors in the majority of women with normo-gonadotrophic normo-estrogenic infertility
Hum. Reprod., February 1, 2003; 18(2): 333 - 337.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
R. C. Andrews, O. Herlihy, D. E. W. Livingstone, R. Andrew, and B. R. Walker
Abnormal Cortisol Metabolism and Tissue Sensitivity to Cortisol in Patients with Glucose Intolerance
J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5587 - 5593.
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J. Clin. Endocrinol. Metab.Home page
J.-M. Fernandez-Real, M. Pugeat, M. Grasa, M. Broch, J. Vendrell, J. Brun, and W. Ricart
Serum Corticosteroid-Binding Globulin Concentration and Insulin Resistance Syndrome: A Population Study
J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4686 - 4690.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
V. Vicennati, L. Ceroni, L. Gagliardi, A. Gambineri, and R. Pasquali
Response of the Hypothalamic-Pituitary-Adrenocortical Axis to High-Protein/Fat and High-Carbohydrate Meals in Women with Different Obesity Phenotypes
J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3984 - 3988.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
E. Rask, B. R. Walker, S. Soderberg, D. E. W. Livingstone, M. Eliasson, O. Johnson, R. Andrew, and T. Olsson
Tissue-Specific Changes in Peripheral Cortisol Metabolism in Obese Women: Increased Adipose 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Activity
J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3330 - 3336.
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Am. J. Respir. Crit. Care Med.Home page
M. S. M. IP, B. LAM, M. M. T. NG, W. K. LAM, K. W. T. TSANG, and K. S. L. LAM
Obstructive Sleep Apnea Is Independently Associated with Insulin Resistance
Am. J. Respir. Crit. Care Med., March 1, 2002; 165(5): 670 - 676.
[Abstract] [Full Text] [PDF]


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Eur Heart JHome page
A. Steptoe and M. Marmot
The role of psychobiological pathways in socio-economic inequalities in cardiovascular disease risk
Eur. Heart J., January 1, 2002; 23(1): 13 - 25.
[Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
R. Pasquali, B. Ambrosi, D. Armanini, F. Cavagnini, E. D. Uberti, G. Del Rio, G. de Pergola, M. Maccario, F. Mantero, M. Marugo, et al.
Cortisol and ACTH Response to Oral Dexamethasone in Obesity and Effects of Sex, Body Fat Distribution, and Dexamethasone Concentrations: A Dose-Response Study
J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 166 - 175.
[Abstract] [Full Text] [PDF]


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Br Med BullHome page
C. D Byrne
Programming other hormones that affect insulin: Type 2 diabetes
Br. Med. Bull., November 1, 2001; 60(1): 153 - 171.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
K. M. Oltmanns, B. Fruehwald-Schultes, W. Kern, J. Born, H. L. Fehm, and A. Peters
Hypoglycemia, But Not Insulin, Acutely Decreases LH and T Secretion in Men
J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4913 - 4919.
[Abstract] [Full Text] [PDF]


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Am. J. Clin. Nutr.Home page
J. C Seidell, L. Perusse, J.-P. Despres, and C. Bouchard
Waist and hip circumferences have independent and opposite effects on cardiovascular disease risk factors: the Quebec Family Study
Am. J. Clinical Nutrition, September 1, 2001; 74(3): 315 - 321.
[Abstract] [Full Text]


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J. Clin. Endocrinol. Metab.Home page
D. S. Jessop, M. F. Dallman, D. Fleming, and S. L. Lightman
Resistance to Glucocorticoid Feedback in Obesity
J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4109 - 4114.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
A. N. Vgontzas, E. O. Bixler, H.-M. Lin, P. Prolo, G. Mastorakos, A. Vela-Bueno, A. Kales, and G. P. Chrousos
Chronic Insomnia Is Associated with Nyctohemeral Activation of the Hypothalamic-Pituitary-Adrenal Axis: Clinical Implications
J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3787 - 3794.
[Abstract] [Full Text] [PDF]


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EndocrinologyHome page
C. Nilsson, B.-M. Larsson, E. Jennische, E. Eriksson, P. Bjorntorp, D. A. York, and A. Holmang
Maternal Endotoxemia Results in Obesity and Insulin Resistance in Adult Male Offspring
Endocrinology, June 1, 2001; 142(6): 2622 - 2630.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
R. Rosmond, M. Chagnon, C. Bouchard, and P. Björntorp
G-308A Polymorphism of the Tumor Necrosis Factor {{alpha}} Gene Promoter and Salivary Cortisol Secretion
J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2178 - 2180.
[Abstract] [Full Text]


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J. Clin. Endocrinol. Metab.Home page
M. G. Dobson, C. P. F. Redfern, N. Unwin, and J. U. Weaver
The N363S Polymorphism of the Glucocorticoid Receptor: Potential Contribution to Central Obesity in Men and Lack of Association with Other Risk Factors for Coronary Heart Disease and Diabetes Mellitus
J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2270 - 2274.
[Abstract] [Full Text]


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BMJHome page
R. Rosmond, C. Bouchard, and P. Björntorp
Tsp509I polymorphism in exon 2 of the glucocorticoid receptor gene in relation to obesity and cortisol secretion: cohort study
BMJ, March 17, 2001; 322(7287): 652 - 653.
[Full Text]


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J. Clin. Endocrinol. Metab.Home page
R. M. Reynolds, B. R. Walker, H. E. Syddall, C. B. Whorwood, P. J. Wood, and D. I. W. Phillips
Elevated Plasma Cortisol in Glucose-Intolerant Men: Differences in Responses to Glucose and Habituation to Venepuncture
J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1149 - 1153.
[Abstract] [Full Text]


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J. Clin. Endocrinol. Metab.Home page
R. M. Reynolds, B. R. Walker, H. E. Syddall, R. Andrew, P. J. Wood, C. B. Whorwood, and D. I. W. Phillips
Altered Control of Cortisol Secretion in Adult Men with Low Birth Weight and Cardiovascular Risk Factors
J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 245 - 250.
[Abstract] [Full Text]


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Cancer Epidemiol. Biomarkers Prev.Home page
A. W. Hsing, J. Deng, I. A. Sesterhenn, F. K. Mostofi, F. Z. Stanczyk, J. Benichou, T. Xie, and Y.-T. Gao
Body Size and Prostate Cancer: A Population-based Case-Control Study in China
Cancer Epidemiol. Biomarkers Prev., December 1, 2000; 9(12): 1335 - 1341.
[Abstract] [Full Text]


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J. Nutr.Home page
S. K. Fried, M. R. Ricci, C. D. Russell, and B. Laferrere
Regulation of Leptin Production in Humans
J. Nutr., December 1, 2000; 130 (12): 3127S - 3131S.
[Abstract] [Full Text] [PDF]


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CirculationHome page
L. Ghiadoni, A. E. Donald, M. Cropley, M. J. Mullen, G. Oakley, M. Taylor, G. O'Connor, J. Betteridge, N. Klein, A. Steptoe, et al.
Mental Stress Induces Transient Endothelial Dysfunction in Humans
Circulation, November 14, 2000; 102(20): 2473 - 2478.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
V. Vicennati and R. Pasquali
Abnormalities of the Hypothalamic-Pituitary-Adrenal Axis in Nondepressed Women with Abdominal Obesity and Relations with Insulin Resistance: Evidence for a Central and a Peripheral Alteration
J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4093 - 4098.
[Abstract] [Full Text]


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Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
B. E. Levin, D. Richard, C. Michel, and R. Servatius
Differential stress responsivity in diet-induced obese and resistant rats
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2000; 279(4): R1357 - R1364.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
A. M. Magarinos and B. S. McEwen
Experimental diabetes in rats causes hippocampal dendritic and synaptic reorganization and increased glucocorticoid reactivity to stress
PNAS, September 26, 2000; 97(20): 11056 - 11061.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
R. Rosmond, Y. C. Chagnon, G. Holm, M. Chagnon, L. Pérusse, K. Lindell, B. Carlsson, C. Bouchard, and P. Björntorp
Hypertension in Obesity and the Leptin Receptor Gene Locus
J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3126 - 3131.
[Abstract] [Full Text]


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J. Clin. Endocrinol. Metab.Home page
A. Johansson, K. Carlström, B. Ahrén, K. Cederquist, E. Krylborg, H. Forsberg, and T. Olsson
Abnormal Cytokine and Adrenocortical Hormone Regulation in Myotonic Dystrophy
J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3169 - 3176.
[Abstract] [Full Text]


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JNCI J Natl Cancer InstHome page
S. E. Sephton, R. M. Sapolsky, H. C. Kraemer, and D. Spiegel
Diurnal Cortisol Rhythm as a Predictor of Breast Cancer Survival
J Natl Cancer Inst, June 21, 2000; 92(12): 994 - 1000.
[Abstract] [Full Text] [PDF]


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Int J EpidemiolHome page
J. Sundquist and M. Winkleby
Country of birth, acculturation status and abdominal obesity in a national sample of Mexican-American women and men
Int. J. Epidemiol., June 1, 2000; 29(3): 470 - 477.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
D. I. W. Phillips, B. R. Walker, R. M. Reynolds, D. E. H. Flanagan, P. J. Wood, C. Osmond, D. J. P. Barker, and C. B. Whorwood
Low Birth Weight Predicts Elevated Plasma Cortisol Concentrations in Adults From 3 Populations
Hypertension, June 1, 2000; 35(6): 1301 - 1306.
[Abstract] [Full Text] [PDF]


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Psychosom. Med.Home page
J. M. Turner-Cobb, S. E. Sephton, C. Koopman, J. Blake-Mortimer, and D. Spiegel
Social Support and Salivary Cortisol in Women With Metastatic Breast Cancer
Psychosom Med, May 1, 2000; 62(3): 337 - 345.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
A. N. Vgontzas, D. A. Papanicolaou, E. O. Bixler, K. Hopper, A. Lotsikas, H.-M. Lin, A. Kales, and G. P. Chrousos
Sleep Apnea and Daytime Sleepiness and Fatigue: Relation to Visceral Obesity, Insulin Resistance, and Hypercytokinemia
J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1151 - 1158.
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Psychosom. Med.Home page
A. Steptoe, M. Cropley, J. Griffith, and C. Kirschbaum
Job Strain and Anger Expression Predict Early Morning Elevations in Salivary Cortisol
Psychosom Med, March 1, 2000; 62(2): 286 - 292.
[Abstract] [Full Text] [PDF]


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EndocrinologyHome page
D. E. W. Livingstone, G. C. Jones, K. Smith, P. M. Jamieson, R. Andrew, C. J. Kenyon, and B. R. Walker
Understanding the Role of Glucocorticoids in Obesity: Tissue-Specific Alterations of Corticosterone Metabolism in Obese Zucker Rats
Endocrinology, February 1, 2000; 141(2): 560 - 563.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
A. Emptoz-Bonneton, P. Cousin, K. Seguchi, G. V. Avvakumov, C. Bully, G. L. Hammond, and M. Pugeat
Novel Human Corticosteroid-Binding Globulin Variant with Low Cortisol-Binding Affinity
J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 361 - 367.
[Abstract] [Full Text]


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J. Clin. Endocrinol. Metab.Home page
G. C. Inglis, M. C. Ingram, C. D. Holloway, L. Swan, D. Birnie, W. S. Hillis, E. Davies, R. Fraser, and J. M. C. Connell
Familial Pattern of Corticosteroids and Their Metabolism in Adult Human Subjects - the Scottish Adult Twin Study
J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 4132 - 4137.
[Abstract] [Full Text]


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Am. J. Physiol. Endocrinol. Metab.Home page
J. M. Solano and L. Jacobson
Glucocorticoids reverse leptin effects on food intake and body fat in mice without increasing NPY mRNA
Am J Physiol Endocrinol Metab, October 1, 1999; 277(4): E708 - E716.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
L. Plat, R. Leproult, M. L’Hermite-Baleriaux, F. Fery, J. Mockel, K. S. Polonsky, and E. Van Cauter
Metabolic Effects of Short-Term Elevations of Plasma Cortisol Are More Pronounced in the Evening Than in the Morning
J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3082 - 3092.
[Abstract] [Full Text]


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J. Clin. Endocrinol. Metab.Home page
J. A. Yanovski, K. D. Miller, T. Kino, T. C. Friedman, G. P. Chrousos, C. Tsigos, and J. Falloon
Endocrine and Metabolic Evaluation of Human Immunodeficiency Virus-Infected Patients with Evidence of Protease Inhibitor-Associated Lipodystrophy
J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 1925 - 1931.
[Abstract] [Full Text]




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