The effect of resistance and aerobic exercises on the hormones of the HPA axis in patients with multiple sclerosis

Document Type : Research Paper I Open Access I Released under (CC BY-NC 4.0) license

Authors

1 Exercise Physiology Department, University of Guilan, Rasht, Iran

2 Department of exercise physiology, University of Guilan, Rasht, IRAN

3 Professor, Department of Neurology, Poursina Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran

Abstract

Aim:      Multiple sclerosis is an autoimmune disease in which the immune system attacks itself and causes damage and inflammation. Cortisol, which is one of the most important hormones of the HPA axis, is directly related to the level of inflammation in the body of MS patients, and research has shown that disruption of this axis may cause changes in the symptoms of MS, so the purpose of this study is to investigate the effect of two aerobic and resistance training programs on hormones. HPA axis in women with MS. Methods: This semi-experimental research was conducted with the participation of 30 women diagnosed with relapsing-remitting MS (with a disability scale ranging from 0 to 5.5) within the age range of 25 to 50. The participants were randomly divided into three groups: aerobic exercise (10 participants), resistance exercise (10 participants), and control group (10 participants). The patients engaged in exercise sessions three times a week for 8 weeks, including warm-up, resistance training, aerobic exercises, and cooldown. All movements were designed to be performed in a home environment. Trainers ensured exercise quality through video calls. Blood samples were collected from the participants' brachial before and after the protocol. Data analysis employed tow-way ANOVA with repeated measures and Bonferroni’s post hoc test. Statistical analysis was conducted using SPSS version 26 software, with a significance level of 0/05. Results:  The studied exercise protocol did not show the ability to make significant changes in the hormones of the hypothalamus-pituitary-adrenal axis in women with MS. In fact the level of cortisol (P=0.946) has been increased but likewise the other hormones such as dopamine (P=0.561), testosterone (P=0.714) and adrenocorticotropin (P=0.933) there were no significant change as a response to training interference. Conclusion:  Based on the results of the current study, 8 weeks of aerobic and resistance exercises (home-based training) did not show the ability to significantly alter the hormonal levels of the HPA axis in patients with depression and relatively limited mobility.
 

Keywords

Main Subjects


  1. McGinley MP, Goldschmidt CH, Rae-Grant AD. Diagnosis and treatment of multiple sclerosis: a review. Jama. 2021;325(8):765-79.
  2. Ghasemi N, Razavi S, Nikzad E. Multiple sclerosis: pathogenesis, symptoms, diagnoses and cell-based therapy. Cell Journal (Yakhteh). 2017;19(1):1.
  3. Tramonti C, Di Martino S, Foglia A, Chisari C. Perceived fatigue, lower limb muscle force and performance fatigability after a rehabilitation program in Multiple Sclerosis. European Journal of Translational Myology. 2020;30(4).
  4. Dalgas U, Ingemann-Hansen T, Stenager E. Physical exercise and MS recommendations. Int Ms J. 2009;16(1):5-11.
  5. Pilutti L, Dlugonski D, Sandroff B, Klaren R, Motl R. Randomized controlled trial of a behavioral intervention targeting symptoms and physical activity in multiple sclerosis. Multiple Sclerosis Journal. 2014;20(5):594-601.
  6. Barry A, Cronin O, Ryan AM, Sweeney B, Yap SM, O'Toole O, et al. Impact of exercise on innate immunity in multiple sclerosis progression and symptomatology. Frontiers in physiology. 2016;7:194.
  7. Smith SM, Vale WW. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues in clinical neuroscience. 2022.
  8. Deckx N, Lee W-P, Berneman ZN, Cools N. Neuroendocrine immunoregulation in multiple sclerosis. Journal of Immunology Research. 2013;2013.
  9. Ghasemi Kahrizsangi G, Salehi H, Heydari L. The effect of a rhythmic motor program on perceptual–motor abilities of educable mentally retarded children. JSMDL. 2012;4(1):75-92. [In Persian]
  10. Hassanpour-Dehkordi A, Jivad N. Comparison of regular aerobic and yoga on the quality of life in patients with multiple sclerosis. Medical Journal of the Islamic Republic of Iran. 2014;28:141. [In Persian]

 

  1. Stojanovich L. Stress and autoimmunity. Autoimmunity reviews. 2010;9(5):A271-A6.
  2. Kemeny ME, Schedlowski M. Understanding the interaction between psychosocial stress and immune-related diseases: a stepwise progression. Brain, behavior, and immunity. 2007;21(8):1009-18.
  3. Chrousos GP. Stressors, stress, and neuroendocrine integration of the adaptive response: The 1997 Hans Selye Memorial Lecture. Annals of the New York Academy of Sciences. 1998;851(1):311-35.
  4. Huitinga I, Erkut ZA, van Beurden D, Swaab DF. The hypothalamo‐pituitary‐adrenal axis in multiple sclerosis. Annals of the New York Academy of Sciences. 2003;992(1):118-28.
  5. Brown RE. An introduction to neuroendocrinology: Cambridge University Press; 1994.
  6. Chrousos GP. Stress and disorders of the stress system. Nat Rev Endocrinol. 2009;5(7):374-81.
  7. Ludwig B, Roy B, Dwivedi Y. Role of HPA and the HPG axis interaction in testosterone-mediated learned helpless behavior. Mol Neurobiol. 2019;56(1):394-405.
  8. Prasad BM, Sorg BA, Ulibarri C, Kalivas PW. Sensitization to Stress and Psychostimulants: Involvement of Dopamine Transmission versus the HPA Axis a. Ann N Y Acad Sci. 1995;771(1):617-25.
  9. Silverman MN, Sternberg EM. Glucocorticoid regulation of inflammation and its functional correlates: from HPA axis to glucocorticoid receptor dysfunction. Annals of the new York Academy of Sciences. 2012;1261(1):55-63.
  10. Kanwar JR. Anti-inflammatory immunotherapy for multiple sclerosis/experimental autoimmune encephalomyelitis (EAE) disease. Current medicinal chemistry. 2005;12(25):2947-62.
  11. Tait AS, Butts CL, Sternberg EM. The role of glucocorticoids and progestins in inflammatory, autoimmune, and infectious disease. Journal of Leucocyte Biology. 2008;84(4):924-31.
  12. Lee DY, Kim E, Choi MH. Technical and clinical aspects of cortisol as a biochemical marker of chronic stress. BMB reports. 2015;48(4):209.
  13. Chaudhuri A, Behan PO. Fatigue in neurological disorders. The lancet. 2004;363(9413):978-88.
  14. Braley TJ, Chervin RD. Fatigue in multiple sclerosis: mechanisms, evaluation, and treatment. Sleep. 2010;33(8):1061-7.
  15. Sangelaji B, Nabavi SM, Estebsari F, Banshi MR, Rashidian H, Jamshidi E, Dastoorpour M. Effect of combination exercise therapy on walking distance, postural balance, fatigue and quality of life in multiple sclerosis patients: a clinical trial study. Iranian Red Crescent Medical Journal. 2014;16(6). [In Persian]

 

  1. Huang X, Zhao X, Li B, Cai Y, Zhang S, Yu F, Wan Q. Biomarkers for evaluating the effects of exercise interventions in patients with MCI or dementia: A systematic review and meta-analysis. Exp Gerontol. 2021;151:111424.
  2. Allen RE, Merkel RA, Young RB. Cellular aspect of muscle growth: myogenic cell proliferation. J Anim Sci. 1979;49(1):115-27.
  3. Hussain R, Ghoumari AM, Bielecki B, Steibel J, Boehm N, Liere P, et al. The neural androgen receptor: a therapeutic target for myelin repair in chronic demyelination. Brain. 2013;136(1):132-46.
  4. Ysrraelit MC, Correale J. Impact of sex hormones on immune function and multiple sclerosis development. Immunology. 2019;156(1):9-22.
  5. Powell DJ, Moss-Morris R, Liossi C, Schlotz W. Circadian cortisol and fatigue severity in relapsing-remitting multiple sclerosis. Psychoneuroendocrinology. 2015;56:120-31.
  6. Talbott SM. The cortisol connection: Why stress makes you fat and ruins your health--and what you can do about it: Hunter House; 2007.
  7. Papenfuss TL, Rogers CJ, Gienapp I, Yurrita M, McClain M, Damico N, et al. Sex differences in experimental autoimmune encephalomyelitis in multiple murine strains. J Neuroimmunol. 2004;150(1-2):59-69.
  8. Constantinescu CS, Farooqi N, O'Brien K, Gran B. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br J Pharmacol. 2011;164(4):1079-106.
  9. Craig B, Brown R, Everhart J. Effects of progressive resistance training on growth hormone and testosterone levels in young and elderly subjects. Mech Ageing Dev. 1989;49(2):159-69.
  10. Pivonello R, Ferone D, Lombardi G, Colao A, Lamberts SW, Hofland LJ. Novel insights in dopamine receptor physiology. European journal of endocrinology. 2007;156(Supplement_1):S13-S21.
  11. پورامیری, عظیمیان, اکبرفهیمی, نازیلا, پیشیاره, ابراهیم, زاده ح. بررسی رابطه ویژگی‌های فردی و بالینی با اختلالات عملکرد اجرایی افراد مالتیپل اسکلروزیس. فصلنامه آرشیو توانبخشی. 2019;20(2):114-23. [In Persian]

 

  1. Manjaly Z-M, Harrison NA, Critchley HD, Do CT, Stefanics G, Wenderoth N, et al. Pathophysiological and cognitive mechanisms of fatigue in multiple sclerosis. Journal of Neurology, Neurosurgery & Psychiatry. 2019;90(6):642-51.
  2. Berk LS, Tan SA, Fry WF, Napier BJ, Lee JW, Hubbard RW, et al. Neuroendocrine and stress hormone changes during mirthful laughter. The American journal of the medical sciences. 1989;298(6):390-6.
  3. Dobryakova E, Genova HM, DeLuca J, Wylie GR. The dopamine imbalance hypothesis of fatigue in multiple sclerosis and other neurological disorders. Frontiers in neurology. 2015;6:52.
  4. Metzger-Peter K, Kremer LD, Edan G, Loureiro De Sousa P, Lamy J, Bagnard D, et al. The TOTEM RRMS (Testosterone Treatment on neuroprotection and Myelin Repair in Relapsing Remitting Multiple Sclerosis) trial: study protocol for a randomized, double-blind, placebo-controlled trial. Trials. 2020;21:1-11.
  5. Najafi P, Moghadasi M. The effect of yoga training on enhancement of Adrenocorticotropic hormone (ACTH) and cortisol levels in female patients with multiple sclerosis. Complement Ther Clin Pract 2017;26:21-5.
  6. Nadeau SE, Lawhern RA. Management of chronic non-cancer pain: a framework. Pain Manag. 2022;12(6):751-77.
  7. Fleming KM, Coote SB, Herring MP. Home-based Pilates for symptoms of anxiety, depression and fatigue among persons with multiple sclerosis: An 8-week randomized controlled trial. Multiple Sclerosis Journal. 2021;27(14):2267-79.
  8. Nussinovitch U, Shoenfeld Y. The role of gender and organ specific autoimmunity. Autoimmunity reviews. 2012;11(6-7):A377-A85.
  9. Najafi P, Moghadasi M. The effect of yoga training on enhancement of Adrenocorticotropic hormone (ACTH) and cortisol levels in female patients with multiple sclerosis. Complementary therapies in clinical practice. 2017;26:21-5.
  10. Bahmani E, Hoseini R, Amiri E. The effect of home-based aerobic training and vitamin D supplementation on fatigue and quality of life in patients with multiple sclerosis during COVID-19 outbreak. Science & Sports. 2022;37(8):710-9.
  11. Hosswini AH, Sedaghati P. The effect of eight weeks of Pilates exercises and myofascial release on balance, trunk muscle endurance and flexibility in people with multiple sclerosis. Studies in Sport Medicine. 2022;13(30):159-84.
  12. DeBolt LS, McCubbin JA. The effects of home-based resistance exercise on balance, power, and mobility in adults with multiple sclerosis. Archives of physical medicine and rehabilitation. 2004;85(2):290-7.
  13. Kim Y, Lai B, Mehta T, Thirumalai M, Padalabalanarayanan S, Rimmer JH, Motl RW. Exercise training guidelines for multiple sclerosis, stroke, and Parkinson’s disease: Rapid review and synthesis. American journal of physical medicine & rehabilitation. 2019;98(7):613.
  14. Rietberg MB, Brooks D, Uitdehaag BM, Kwakkel G. Exercise therapy for multiple sclerosis. Cochrane database of systematic reviews. 2005(1).
  15. Morrison EH, Cooper DM, White LJ, Larson J, Leu S-Y, Zaldivar F, Ng AV. Ratings of perceived exertion during aerobic exercise in multiple sclerosis. Archives of physical medicine and rehabilitation. 2008;89(8):1570-4.
  16. Bergh FT, Kümpfel T, Trenkwalder C, Rupprecht R, Holsboer F. Dysregulation of the hypothalamo-pituitary-adrenal axis is related to the clinical course of MS. Neurology. 1999;53(4):772-.
  17. Soleimani A, Ezabadi SG, Möhn N, Esfandabadi ZM, Khosravizadeh Z, Skripuletz T, Azimzadeh M. Influence of hormones in multiple sclerosis: focus on the most important hormones. Metabolic Brain Disease. 2023;38(3):739-47.
  18. Melnikov M, Sviridova A, Rogovskii V, Kudrin V, Murugin V, Boyko A, Pashenkov M. The role of D2-like dopaminergic receptor in dopamine-mediated modulation of Th17-cells in multiple sclerosis. Current Neuropharmacology. 2022;20(8):1632-9.
  19. Osorio-Barrios F, Navarro G, Campos J, Ugalde V, Prado C, Raïch I, et al. The heteromeric complex formed by dopamine receptor D5 and CCR9 leads the gut homing of CD4+ T cells upon inflammation. Cellular and molecular gastroenterology and hepatology. 2021;12(2):489-506.
  20. Melnikov M, Pashenkov M, Boyko A. Dopaminergic receptor targeting in multiple sclerosis: is there therapeutic potential? International Journal of Molecular Sciences. 2021;22(10):5313.
  21. Sutoo De, Akiyama K. Regulation of brain function by exercise. Neurobiology of disease. 2003;13(1):1-14.
  22. Petzinger GM, Fisher BE, McEwen S, Beeler JA, Walsh JP, Jakowec MW. Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease. The Lancet Neurology. 2013;12(7):716-26.
  23. Langeskov-Christensen M, Bisson EJ, Finlayson ML, Dalgas U. Potential pathophysiological pathways that can explain the positive effects of exercise on fatigue in multiple sclerosis: a scoping review. Journal of the neurological sciences. 2017;373:307-20.
  24. Gorrell S, Shott ME, Frank GK. Associations between aerobic exercise and dopamine-related reward-processing: Informing a model of human exercise engagement. Biological Psychology. 2022;171:108350.
  25. Herman J, McKlveen J, Solomon M, Carvalho-Netto E, Myers B. Neural regulation of the stress response: glucocorticoid feedback mechanisms. Brazilian journal of medical and biological research. 2012;45:292-8.
  26. Reynolds ER, Ashbaugh AD, Hockenberry BJ, McGrew CA. Multiple sclerosis and exercise: a literature review. Current sports medicine reports. 2018;17(1):31-5.
  27. Heesen C, Gold SM, Raji A, Wiedemann K, Schulz K-H. Cognitive impairment correlates with hypothalamo–pituitary–adrenal axis dysregulation in multiple sclerosis. Psychoneuroendocrinology. 2002;27(4):505-17.
  28. Barskova T, Oesterreich R. Post-traumatic growth in people living with a serious medical condition and its relations to physical and mental health: A systematic review. Disability and rehabilitation. 2009;31(21):1709-33.
  29. Hill E, Zack E, Battaglini C, Viru M, Viru A, Hackney A. Exercise and circulating cortisol levels: the intensity threshold effect. Journal of endocrinological investigation. 2008;31:587-91.
  30. Bove R, Musallam A, Healy B, Raghavan K, Glanz B, Bakshi R, et al. Low testosterone is associated with disability in men with multiple sclerosis. Multiple Sclerosis Journal. 2014;20(12):1584-92.
  31. Kjølhede T, Dalgas U, Gade A, Bjerre M, Stenager E, Petersen T, Vissing K. Acute and chronic cytokine responses to resistance exercise and training in people with multiple sclerosis. Scandinavian journal of medicine & science in sports. 2016;26(7):824-34.
  32. De Spiegeleer A, Beckwée D, Bautmans I, Petrovic M. Pharmacological interventions to improve muscle mass, muscle strength and physical performance in older people: an umbrella review of systematic reviews and meta-analyses. Drugs & aging. 2018;35:719-34.
  33. Chitnis T. The role of testosterone in MS risk and course. Multiple Sclerosis Journal. 2018;24(1):36-41.
  34. Huang X, Zhao X, Li B, Cai Y, Zhang S, Yu F, Wan Q. Biomarkers for evaluating the effects of exercise interventions in patients with MCI or dementia: A systematic review and meta-analysis. Experimental Gerontology. 2021;151:111424.
  35. Musella A, Fresegna D, Rizzo FR, Gentile A, De Vito F, Caioli S, et al. ‘Prototypical’proinflammatory cytokine (IL-1) in multiple sclerosis: role in pathogenesis and therapeutic targeting. Expert Opinion on Therapeutic Targets. 2020;24(1):37-46.
  36. Gold SM, Voskuhl RR. Estrogen and testosterone therapies in multiple sclerosis. Progress in brain research. 2009;175:239-51.
  37. Bellavance M-A, Rivest S. The HPA–immune axis and the immunomodulatory actions of glucocorticoids in the brain. Frontiers in immunology. 2014;5:136.
  38. Myhr K, Mellgren S. Corticosteroids in the treatment of multiple sclerosis. Acta Neurologica Scandinavica. 2009;120:73-80.
  39. Marketon JIW, Glaser R. Stress hormones and immune function. Cellular immunology. 2008;252(1-2):16-26.
  40. Guilliams TG, Edwards L. Chronic stress and the HPA axis. The standard. 2010;9(2):1-12.
  41. Allen RE, Merkel RA, Young RB. Cellular aspect of muscle growth: myogenic cell proliferation. Journal of animal science. 1979;49(1):115-27.