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Published in: Sports Medicine - Open 1/2017

Open Access 01-12-2017 | Original Research Article

Hypothalamic-Pituitary-Adrenal (HPA) Axis Functioning in Overtraining Syndrome: Findings from Endocrine and Metabolic Responses on Overtraining Syndrome (EROS)—EROS-HPA Axis

Authors: Flavio A. Cadegiani, Claudio E. Kater

Published in: Sports Medicine - Open | Issue 1/2017

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Abstract

Background

Overtraining syndrome (OTS) results from excessive training load without adequate recovery and leads to decreased performance and fatigue. The pathophysiology of OTS in athletes is not fully understood, which makes accurate diagnosis difficult. Previous studies indicate that alterations in the hypothalamus-pituitary-adrenal (HPA) axis may be responsible for OTS; however, the data is not conclusive. This study aimed to compare, through gold standard and exercise-independent tests, the response of the HPA axis in OTS-affected athletes (OTS group) to healthy physically active subjects (ATL group) and healthy non-active subjects (NCS group).

Methods

Selected subjects were evaluated for cortisol response to a 250-μg cosyntropin stimulation test (CST), cortisol and adrenocorticotropic hormone (ACTH) responses during an insulin tolerance test (ITT), and salivary cortisol rhythm (SCR).

Results

A total of 51 subjects were included (OTS, n = 14; ATL, n = 25; and NCS, n = 12). Cortisol response in the CST was similar among the three groups. Conversely, mean cortisol response during an ITT was significantly higher in ATL (21.7 μg/dL; increase = 9.2 μg/dL) compared to OTS (17.9 μg/dL; 6.3 μg/dL) and NCS (16.9 μg/dL; 6.0 μg/dL) (p ≤ 0.001; p = 0.01). Likewise, median ACTH response during an ITT was significantly higher in ATL (91.4 pg/mL; increase = 45.1 pg/mL) compared to OTS (30.3 pg/mL; 9.7 pg/mL) and NCS (51.4 pg/mL; 38.0 pg/mL) (p = 0.006; p = 0.004). For SCR, mean cortisol 30 min after awakening was significantly higher in ATL (500 ng/dL) compared to OTS (323 ng/dL) and NCS (393 ng/dL) (p = 0.004). We identified the following cutoffs that could help exclude or confirm OTS: cortisol level at 30 min after awakening (exclusion = > 530 ng/dL); cortisol response to ITT (exclusion = > 20.5 μg/dL; confirmation = < 17 μg/dL or increase < 9.5 μg/dL); and ACTH response (exclusion = > 106 pg/mL or increase > 70 pg/mL; confirmation = < 35 pg/mL and increase < 14.5 pg/mL).

Conclusion

The findings of the present study showed that healthy athletes disclose adaptions to exercises that helped improve sport-specific performance, whereas this sort of hormonal conditioning was at least partially lost in OTS, which may explain the decrease in performance in OTS.
Literature
1.
go back to reference Meeusen R, Duclos M, Foster C, Fry A, Gleeson M, Nieman D, Raglin J, Rietjens G, Steinacker J, Urhausen A, European College of Sport Science; American College of Sports Medicine. Prevention, diagnosis, and treatment of the overtraining syndrome: joint consensus statement of the European College of Sport Science and the American College of Sports Medicine. Med Sci Sports Exerc. 2013 Jan;45(1):186–205.CrossRefPubMed Meeusen R, Duclos M, Foster C, Fry A, Gleeson M, Nieman D, Raglin J, Rietjens G, Steinacker J, Urhausen A, European College of Sport Science; American College of Sports Medicine. Prevention, diagnosis, and treatment of the overtraining syndrome: joint consensus statement of the European College of Sport Science and the American College of Sports Medicine. Med Sci Sports Exerc. 2013 Jan;45(1):186–205.CrossRefPubMed
2.
go back to reference Le Meur Y, Hausswirth C, Natta F, et al. A multidisciplinary approach to overreaching detection in endurance trained athletes. J Appl Physiol. 1 February 2013;114(3):411–20.CrossRefPubMed Le Meur Y, Hausswirth C, Natta F, et al. A multidisciplinary approach to overreaching detection in endurance trained athletes. J Appl Physiol. 1 February 2013;114(3):411–20.CrossRefPubMed
3.
go back to reference Nederhof E, Zwerver J, Brink M, Meeusen R, Lemmink K. Different diagnostic tools in nonfunctional overreaching. Int J Sports Med. 2008 Jul;29(7):590–7.CrossRefPubMed Nederhof E, Zwerver J, Brink M, Meeusen R, Lemmink K. Different diagnostic tools in nonfunctional overreaching. Int J Sports Med. 2008 Jul;29(7):590–7.CrossRefPubMed
4.
go back to reference Lehmann M, Foster C, Keul J. Overtraining in endurance athletes: a brief review. Med Sci Sports Exerc. 1993;25(7):854–62.CrossRefPubMed Lehmann M, Foster C, Keul J. Overtraining in endurance athletes: a brief review. Med Sci Sports Exerc. 1993;25(7):854–62.CrossRefPubMed
6.
go back to reference Thiel C, Vogt L, Bürklein M, Rosenhagen A, Hübscher M, Banzer W. Functional overreaching during preparation training of elite tennis professionals. J Hum Kinet. 2011 Jun;28:79–89.CrossRefPubMedPubMedCentral Thiel C, Vogt L, Bürklein M, Rosenhagen A, Hübscher M, Banzer W. Functional overreaching during preparation training of elite tennis professionals. J Hum Kinet. 2011 Jun;28:79–89.CrossRefPubMedPubMedCentral
7.
go back to reference Meeusen R, Nederhof E, Buyse L, Roelands B, De Schutter G, Piacentini MF. Diagnosing overtraining in athletes using the two-bout exercise protocol. Br J Sports Med. 2010;44(9):642–8.CrossRefPubMed Meeusen R, Nederhof E, Buyse L, Roelands B, De Schutter G, Piacentini MF. Diagnosing overtraining in athletes using the two-bout exercise protocol. Br J Sports Med. 2010;44(9):642–8.CrossRefPubMed
8.
go back to reference Meeusen R, Piacentini MF, Busschaert B, Buyse L, De Schutter G, Stray-Gundersen J. Hormonal responses in athletes: the use of a two bout exercise protocol to detect subtle differences in (over)training status. Eur J Appl Physiol. 2004 Mar;91(2–3):140–6.CrossRefPubMed Meeusen R, Piacentini MF, Busschaert B, Buyse L, De Schutter G, Stray-Gundersen J. Hormonal responses in athletes: the use of a two bout exercise protocol to detect subtle differences in (over)training status. Eur J Appl Physiol. 2004 Mar;91(2–3):140–6.CrossRefPubMed
9.
go back to reference Urhausen A, Gabriel HH, Kindermann W. Impaired pituitary hormonal response to exhaustive exercise in overtrained endurance athletes. Med Sci Sports Exerc. 1998 Mar;30(3):407–14.CrossRefPubMed Urhausen A, Gabriel HH, Kindermann W. Impaired pituitary hormonal response to exhaustive exercise in overtrained endurance athletes. Med Sci Sports Exerc. 1998 Mar;30(3):407–14.CrossRefPubMed
10.
go back to reference Barron G, Noakes T, Levy W, Smidt C, Millar R. Hypothalamic dysfunction in overtrained athletes. J Clin Endocrinol Metab. 1985;60:803–6. Cizza G, Kvetnansky R, Tartaglia M, Blackman M, Chrousos G,CrossRefPubMed Barron G, Noakes T, Levy W, Smidt C, Millar R. Hypothalamic dysfunction in overtrained athletes. J Clin Endocrinol Metab. 1985;60:803–6. Cizza G, Kvetnansky R, Tartaglia M, Blackman M, Chrousos G,CrossRefPubMed
11.
go back to reference Gold P. Immobolisation stress rapidly decreases hypothalamic corticotropin-releasing hormone secretion in vitro in the male 344/N Fischer rat. Life Sci. 1993;53:233–40.CrossRefPubMed Gold P. Immobolisation stress rapidly decreases hypothalamic corticotropin-releasing hormone secretion in vitro in the male 344/N Fischer rat. Life Sci. 1993;53:233–40.CrossRefPubMed
12.
go back to reference Duclos M, Corcuff J-B, Arsac L, et al. Corticotroph axis sensitivity after exercise in endurance-trained athletes. Clin Endocrinol. 1998;8:493–501.CrossRef Duclos M, Corcuff J-B, Arsac L, et al. Corticotroph axis sensitivity after exercise in endurance-trained athletes. Clin Endocrinol. 1998;8:493–501.CrossRef
14.
go back to reference Ryan R, Booth S, Spathis A, Mollart S, Clow A. Use of salivary diurnal cortisol as an outcome measure in randomised controlled trials: a systematic review. Ann Behav Med. 2016 Apr;50(2):210–36.CrossRefPubMedPubMedCentral Ryan R, Booth S, Spathis A, Mollart S, Clow A. Use of salivary diurnal cortisol as an outcome measure in randomised controlled trials: a systematic review. Ann Behav Med. 2016 Apr;50(2):210–36.CrossRefPubMedPubMedCentral
15.
go back to reference Stalder T, Kirschbaum C, Kudielka BM. Assessment of the cortisol awakening response: expert consensus guidelines. Psychoneuroendocrinology. 2016 Jan;63:414–32.CrossRefPubMed Stalder T, Kirschbaum C, Kudielka BM. Assessment of the cortisol awakening response: expert consensus guidelines. Psychoneuroendocrinology. 2016 Jan;63:414–32.CrossRefPubMed
16.
go back to reference Oosterholt BG, Maes JH, Van der Linden D, Verbraak MJ, Kompier MA. Burnout and cortisol: evidence for a lower cortisol awakening response in both clinical and non-clinical burnout. J Psychosom Res. 2015 May;78(5):445–51.CrossRefPubMed Oosterholt BG, Maes JH, Van der Linden D, Verbraak MJ, Kompier MA. Burnout and cortisol: evidence for a lower cortisol awakening response in both clinical and non-clinical burnout. J Psychosom Res. 2015 May;78(5):445–51.CrossRefPubMed
17.
go back to reference Powell DJ, Liossi C, Moss-Morris R, Schlotz W. Unstimulated cortisol secretory activity in everyday life and its relationship with fatigue and chronic fatigue syndrome: a systematic review and subset meta-analysis. Psychoneuroendocrinology. 2013 Nov;38(11):2405–22.CrossRefPubMed Powell DJ, Liossi C, Moss-Morris R, Schlotz W. Unstimulated cortisol secretory activity in everyday life and its relationship with fatigue and chronic fatigue syndrome: a systematic review and subset meta-analysis. Psychoneuroendocrinology. 2013 Nov;38(11):2405–22.CrossRefPubMed
18.
go back to reference Slivka DR, Hailes WS, Cuddy JS, Ruby BC. Effects of 21 days of intensified training on markers of overtraining. J Strength Cond Res. 2010 Oct;24(10):2604–12.CrossRefPubMed Slivka DR, Hailes WS, Cuddy JS, Ruby BC. Effects of 21 days of intensified training on markers of overtraining. J Strength Cond Res. 2010 Oct;24(10):2604–12.CrossRefPubMed
19.
go back to reference Rietjens GJ, Kuipers H, Adam JJ, et al. Physiological, biochemical and psychological markers of strenuous training-induced fatigue. Int J Sports Med. 2005 Jan-Feb;26(1):16–26.CrossRefPubMed Rietjens GJ, Kuipers H, Adam JJ, et al. Physiological, biochemical and psychological markers of strenuous training-induced fatigue. Int J Sports Med. 2005 Jan-Feb;26(1):16–26.CrossRefPubMed
20.
go back to reference Coutts AJ, Reaburn P, Piva TJ, Rowsell GJ. Monitoring for overreaching in rugby league players. Eur J Appl Physiol. 2007 Feb;99(3):313–24.CrossRefPubMed Coutts AJ, Reaburn P, Piva TJ, Rowsell GJ. Monitoring for overreaching in rugby league players. Eur J Appl Physiol. 2007 Feb;99(3):313–24.CrossRefPubMed
21.
go back to reference Schmikli SL, de Vries WR, Brink MS, Backx FJ. Monitoring performance, pituitary-adrenal hormones and mood profiles: how to diagnose non-functional over-reaching in male elite junior soccer players. Br J Sports Med. 2012 Nov;46(14):1019–23.CrossRefPubMed Schmikli SL, de Vries WR, Brink MS, Backx FJ. Monitoring performance, pituitary-adrenal hormones and mood profiles: how to diagnose non-functional over-reaching in male elite junior soccer players. Br J Sports Med. 2012 Nov;46(14):1019–23.CrossRefPubMed
22.
go back to reference Tanskanen MM, Kyröläinen H, Uusitalo AL, Huovinen J, Nissilä J, Kinnunen H, Atalay M, Häkkinen K. Serum sex hormone-binding globulin and cortisol concentrations are associated with overreaching during strenuous military training. J Strength Cond Res. 2011 Mar;25(3):787–97.CrossRefPubMed Tanskanen MM, Kyröläinen H, Uusitalo AL, Huovinen J, Nissilä J, Kinnunen H, Atalay M, Häkkinen K. Serum sex hormone-binding globulin and cortisol concentrations are associated with overreaching during strenuous military training. J Strength Cond Res. 2011 Mar;25(3):787–97.CrossRefPubMed
23.
go back to reference Kraemer WJ, French DN, Paxton NJ. Changes in exercise performance and hormonal concentrations over a big ten soccer season in starters and nonstarters. J Strength Cond Res. 2004 Feb;18(1):121–8.PubMed Kraemer WJ, French DN, Paxton NJ. Changes in exercise performance and hormonal concentrations over a big ten soccer season in starters and nonstarters. J Strength Cond Res. 2004 Feb;18(1):121–8.PubMed
24.
go back to reference Hug M, Mullis PE, Vogt M, Ventura N, Hoppeler H. Training modalities: over-reaching and over-training in athletes, including a study of the role of hormones. Best Pract Res Clin Endocrinol Metab. 2003 Jun;17(2):191–209.CrossRefPubMed Hug M, Mullis PE, Vogt M, Ventura N, Hoppeler H. Training modalities: over-reaching and over-training in athletes, including a study of the role of hormones. Best Pract Res Clin Endocrinol Metab. 2003 Jun;17(2):191–209.CrossRefPubMed
25.
go back to reference Steinacker JM, Lormes W, Kellmann M, et al. Training of junior rowers before world championships. Effects on performance, mood state and selected hormonal and metabolic responses. J Sports Med Phys Fitness. 2000 Dec;40(4):327–35.PubMed Steinacker JM, Lormes W, Kellmann M, et al. Training of junior rowers before world championships. Effects on performance, mood state and selected hormonal and metabolic responses. J Sports Med Phys Fitness. 2000 Dec;40(4):327–35.PubMed
26.
go back to reference Fry AC, Kraemer WJ, Ramsey LT. Pituitary-adrenal-gonadal responses to high-intensity resistance exercise overtraining. J Appl Physiol (1985). 1998 Dec;85(6):2352–9. Fry AC, Kraemer WJ, Ramsey LT. Pituitary-adrenal-gonadal responses to high-intensity resistance exercise overtraining. J Appl Physiol (1985). 1998 Dec;85(6):2352–9.
27.
go back to reference Fry RW, Morton AR, Garcia-Webb P, Crawford GP, Keast D. Biological responses to overload training in endurance sports. Eur J Appl Physiol Occup Physiol. 1992;64(4):335–44.CrossRefPubMed Fry RW, Morton AR, Garcia-Webb P, Crawford GP, Keast D. Biological responses to overload training in endurance sports. Eur J Appl Physiol Occup Physiol. 1992;64(4):335–44.CrossRefPubMed
28.
go back to reference Lehmann M, Gastmann U, Petersen KG, Bachl SA, Khalaf AN, Fischer S, Keul J. Training-overtraining: performance, and hormone levels, after a defined increase in training volume versus intensity in experienced middle- and long-distance runners. Br J Sports Med. 1992 December;26(4):233–42.CrossRefPubMedPubMedCentral Lehmann M, Gastmann U, Petersen KG, Bachl SA, Khalaf AN, Fischer S, Keul J. Training-overtraining: performance, and hormone levels, after a defined increase in training volume versus intensity in experienced middle- and long-distance runners. Br J Sports Med. 1992 December;26(4):233–42.CrossRefPubMedPubMedCentral
29.
go back to reference O'Connor PJ, Morgan WP, Raglin JS, Barksdale CM, Kalin NH. Mood state and salivary cortisol levels following overtraining in female swimmers. Psychoneuroendocrinology. 1989;14(4):303–10.CrossRefPubMed O'Connor PJ, Morgan WP, Raglin JS, Barksdale CM, Kalin NH. Mood state and salivary cortisol levels following overtraining in female swimmers. Psychoneuroendocrinology. 1989;14(4):303–10.CrossRefPubMed
30.
go back to reference Barron LJ, Noakes TD, Levy W, Smith C, Millar RP. Hypothalamic dysfunction in overtrained athletes. J Clin Endocrinol Metab. 1985;60(4):803–6.CrossRefPubMed Barron LJ, Noakes TD, Levy W, Smith C, Millar RP. Hypothalamic dysfunction in overtrained athletes. J Clin Endocrinol Metab. 1985;60(4):803–6.CrossRefPubMed
31.
go back to reference Cadegiani FA, Kater CE. Rationale, design, material, methods, subject selection and baseline characteristics of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study. Available at: https://osf.io/bhpq9/. Cadegiani FA, Kater CE. Rationale, design, material, methods, subject selection and baseline characteristics of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study. Available at: https://​osf.​io/​bhpq9/​.
32.
go back to reference Ospina NS, Al Nofal A, Bancos I, Javed A, Benkhadra K, Kapoor E, et al. ACTH stimulation tests for the diagnosis of adrenal insufficiency: systematic review and meta-analysis. J Clin Endocrinol Metab. 2016;101(2):427–34.CrossRefPubMed Ospina NS, Al Nofal A, Bancos I, Javed A, Benkhadra K, Kapoor E, et al. ACTH stimulation tests for the diagnosis of adrenal insufficiency: systematic review and meta-analysis. J Clin Endocrinol Metab. 2016;101(2):427–34.CrossRefPubMed
33.
go back to reference Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, et al. Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(2):364–89.CrossRefPubMed Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, et al. Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(2):364–89.CrossRefPubMed
34.
go back to reference Roberts AC, McClure RD, Weiner RI, Brooks GA. Overtraining affects male reproductive status. Fertil Steril. 1993 Oct;60(4):686–92.CrossRefPubMed Roberts AC, McClure RD, Weiner RI, Brooks GA. Overtraining affects male reproductive status. Fertil Steril. 1993 Oct;60(4):686–92.CrossRefPubMed
35.
go back to reference Bae YJ, Kratzsch J. Corticosteroid-binding globulin: modulating mechanisms of bioavailability of cortisol and its clinical implications. Best Pract Res Clin Endocrinol Metab. 2015 Oct;29(5):761–72.CrossRefPubMed Bae YJ, Kratzsch J. Corticosteroid-binding globulin: modulating mechanisms of bioavailability of cortisol and its clinical implications. Best Pract Res Clin Endocrinol Metab. 2015 Oct;29(5):761–72.CrossRefPubMed
36.
go back to reference Perogamyros I, Aarons L, Miller AG, Trainer PJ, Ray DW. Corticosteroid-binding globulin regulates cortisol pharmacokinetics. Clin Endocrinol. 2011 Jan;74(1):30–6.CrossRef Perogamyros I, Aarons L, Miller AG, Trainer PJ, Ray DW. Corticosteroid-binding globulin regulates cortisol pharmacokinetics. Clin Endocrinol. 2011 Jan;74(1):30–6.CrossRef
37.
go back to reference Brooks K, Carter J. Overtraining, exercise and adrenal insufficiency. J Nov Physiother. 2013;3(125). Brooks K, Carter J. Overtraining, exercise and adrenal insufficiency. J Nov Physiother. 2013;3(125).
38.
go back to reference Angeli A, Minetto M, Dovio A, Paccotti P. The overtraining syndrome in athletes: a stress-related disorder. J Endocrinol Investig. 2004;27(6):603–12.CrossRef Angeli A, Minetto M, Dovio A, Paccotti P. The overtraining syndrome in athletes: a stress-related disorder. J Endocrinol Investig. 2004;27(6):603–12.CrossRef
39.
go back to reference Urhausen A, Gabriel H, Kindermann W. Blood hormones as markers of training stress and overtraining. Sports Med. 1995;20:251–76.CrossRefPubMed Urhausen A, Gabriel H, Kindermann W. Blood hormones as markers of training stress and overtraining. Sports Med. 1995;20:251–76.CrossRefPubMed
40.
go back to reference Budgett R, Newsholme E, Lehmann M, et al. Redefining the overtraining syndrome as the unexplained underperformance syndrome. Br J Sports Med. 2000;34:67–8.CrossRefPubMedPubMedCentral Budgett R, Newsholme E, Lehmann M, et al. Redefining the overtraining syndrome as the unexplained underperformance syndrome. Br J Sports Med. 2000;34:67–8.CrossRefPubMedPubMedCentral
Metadata
Title
Hypothalamic-Pituitary-Adrenal (HPA) Axis Functioning in Overtraining Syndrome: Findings from Endocrine and Metabolic Responses on Overtraining Syndrome (EROS)—EROS-HPA Axis
Authors
Flavio A. Cadegiani
Claudio E. Kater
Publication date
01-12-2017
Publisher
Springer International Publishing
Published in
Sports Medicine - Open / Issue 1/2017
Print ISSN: 2199-1170
Electronic ISSN: 2198-9761
DOI
https://doi.org/10.1186/s40798-017-0113-0

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