Title
Author
DOI
Article Type
Special Issue
Volume
Issue
Evaluation of the salivary biomarker cortisol in patients with temporomandibular disorders
1Institute for Occlusion and Orofacial Pain, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal
2Department of Surgery, University of Salamanca, 37007 Salamanca, Spain
3Biomedical Research Intitute of Salamanca (IBSAL), 37007 Salamanca, Spain
DOI: 10.22514/jofph.2026.007 Vol.40,Issue 1,January 2026 pp.81-87
Submitted: 25 July 2025 Accepted: 12 September 2025
Published: 12 January 2026
*Corresponding Author(s): Nansi Lopez-Valverde E-mail: nlovalher@usal.es
Background: Temporomandibular Disorders (TMD) are musculoskeletal and neuro-muscular conditions involving the temporomandibular joint (TMJ), masticatory muscles, and related structures. Stress can trigger dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to increased cortisol secretion. Salivary cortisol assessment provides a non-invasive method to investigate this relationship. Methods: A total of 98 participants were recruited—49 patients diagnosed with TMD and 49 healthy controls—at the Faculty of Medicine of the University of Coimbra. Participants were evaluated according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Saliva samples were collected between 9:00 and 11:00 AM, processed with Enzyme-Linked Immunosorbent Assay (ELISA), and analyzed statistically using Shapiro-Wilk and Mann-Whitney tests, with a 95% confidence level. Results: Salivary cortisol levels were significantly higher in TMD patients (mean = 17.55 nmol/L) compared with controls (mean = 11.09 nmol/L; p = 0.0032). No significant correlations were found between age and cortisol levels. Conclusions: Patients with TMD present higher salivary cortisol levels, suggesting dysregulation of the HPA axis associated with stress. These findings support the integration of psychosocial factors into the management of TMD. Clinical Trial Registration: ClinicalTrials.gov identifier NCT06874868.
Temporomandibular disorders; Stress; Anxiety; Biomarker; Cortisol
Bruno Macedo de Sousa,Nansi Lopez-Valverde,Carla Cardoso,Antonio Lopez-Valverde2,Maria J. Rodrigues,Jose A. Blanco Rueda. Evaluation of the salivary biomarker cortisol in patients with temporomandibular disorders. Journal of Oral & Facial Pain and Headache. 2026. 40(1);81-87.
[1] de Leeuw R, Klasser GD. Orofacial pain: guidelines for assessment, diagnosis, and management. 6th edn. Quintessence Publishing: Hanover Park. 2018.
[2] Valesan LF, Da-Cas CD, Réus JC, Denardin ACS, Garanhani RR, Bonotto D, et al. Prevalence of temporomandibular disorders: a systematic review and meta-analysis. Clinical Oral Investigations. 2021; 25: 441–453.
[3] Kapos FP, Exposto FG, Oyarzo JF, Durham J. Temporomandibular disorders: a review of current concepts in aetiology, diagnosis and management. Oral Surgery. 2020; 13: 321–334.
[4] Chisnoiu AM, Picos AM, Popa S, Chisnoiu PD, Lascu L, Picos A, et al. Factors involved in the etiology of temporomandibular disorders: a literature review. Clujul Medical. 2015; 88: 473–478.
[5] Türp JC, Schindler HJ. Screening for temporomandibular disorders: a sensible approach? Der Schmerz. 2020; 34: 13–20. (In German)
[6] List T, Jensen RH. Temporomandibular disorders: old ideas and new concepts. Cephalalgia. 2017; 37: 692–704.
[7] Schiffman E, Ohrbach R, Truelove E, Look J, Anderson G, Goulet JP, et al.; International RDC/TMD Consortium Network, International association for Dental Research; Orofacial Pain Special Interest Group, International Association for the Study of Pain. Diagnostic criteria for temporomandibular disorders (DC/TMD) for clinical and research applications: recommendations of the International RDC/TMD Consortium Network* and Orofacial Pain Special Interest Group†. Journal of Oral & Facial Pain and Headache. 2014; 28: 6–27.
[8] Miller DB, O’Callaghan JP. Neuroendocrine aspects of the response to stress. Metabolism. 2002; 51: 5–10.
[9] Mbiydzenyuy NE, Qulu LA. Stress, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis, and aggression. Metabolic Brain Disease. 2024; 39: 1613–1626.
[10] Androulakis IP. Circadian rhythms and the HPA axis: a systems view. WIREs Mechanisms of Disease. 2021; 13: e1518.
[11] Noushad S, Ahmed S, Ansari B, Mustafa UH, Saleem Y, Hazrat H. Physiological biomarkers of chronic stress: a systematic review. International Journal of Health Sciences. 2021; 15: 46–59.
[12] Laufer S, Engel S, Lupien S, Knaevelsrud C, Schumacher S. The Cortisol Assessment List (CoAL) a tool to systematically document and evaluate cortisol assessment in blood, urine and saliva. Comprehensive Psychoneuroendocrinology. 2021; 9: 100108.
[13] Shekhar A, Maddheshiya N, Nair V, Rastogi V, Srivastava A, Singh AK. Salivary biomarkers and temporomandibular disorders: a systematic review. National Journal of Maxillofacial Surgery. 2023; 14: 354–359.
[14] Kudielka BM, Gierens A, Hellhammer DH, Wüst S, Schlotz W. Salivary cortisol in ambulatory assessment—some dos, some don’ts, and some open questions. Psychosomatic Medicine. 2012; 74: 418–431.
[15] Dongiovanni P, Meroni M, Casati S, Goldoni R, Thomaz DV, Kehr NS, et al. Salivary biomarkers: novel noninvasive tools to diagnose chronic inflammation. International Journal of Oral Science. 2023; 15: 27.
[16] Staniszewski K, Lygre H, Bifulco E, Kvinnsland S, Willassen L, Helgeland E, et al. Temporomandibular disorders related to stress and hpa-axis regulation. Pain Research and Management. 2018; 2018: 7020751.
[17] Soria-Reyes LM, Cerezo MV, Alarcón R, Blanca MJ. Psychometric properties of the perceived stress scale (pss-10) with breast cancer patients. Stress and Health. 2023; 39: 115–124.
[18] Cao CH, Dang CY, Zheng X, Chen WG, Chen IH, Gamble JH. The psychometric properties of the DASS-21 and its association with problematic Internet use among Chinese college freshmen. Healthcare. 2023; 11: 700.
[19] Alam MK, Zaman MU, Alqhtani NR, Alqahtani AS, Alqahtani F, Cicciù M, et al. Salivary biomarkers and temporomandibular disorders: a systematic review conducted according to prisma guidelines and the cochrane handbook for systematic reviews of interventions. Journal of Oral Rehabilitation. 2024; 51: 416–426.
[20] AlSahman L, AlBagieh H, AlSahman R. Is there a relationship between salivary cortisol and temporomandibular disorder: a systematic review. Diagnostics. 2024; 14: 1235.
[21] Fillingim RB, Ohrbach R, Greenspan JD, Knott C, Diatchenko L, Dubner R, et al. Psychological factors associated with development of tmd: the OPPERA prospective cohort study. The Journal of Pain. 2013; 14: T75–T90.
[22] Venkatesh SB, Shetty SS, Kamath V. Prevalence of temporomandibular disorders and its correlation with stress and salivary cortisol levels among students. Pesquisa Brasileira em Odontopediatria e Clínica Integrada. 2021; 21: e0120.
[23] AlSahman L, AlBagieh H, AlSahman R, Mehta NR, Correa LP. Does salivary cortisol serve as a potential biomarker for temporomandibular disorders in adults? BMC Oral Health. 2024; 24: 1364.
[24] Chinthakanan S, Laosuwan K, Boonyawong P, Kumfu S, Chattipakorn N, Chattipakorn SC. Reduced heart rate variability and increased salivary cortisol in patients with TMD. Archives of Oral Biology. 2018; 90: 125–129.
[25] Ohrbach R, Dworkin SF. The evolution of TMD diagnosis. Journal of Dental Research. 2016; 95: 1093–1101.
[26] Peck CC, Goulet JP, Lobbezoo F, Schiffman EL, Alstergren P, Anderson GC, et al. Expanding the taxonomy of the diagnostic criteria for temporomandibular disorders. Journal of Oral Rehabilitation. 2014; 41: 2–23.
[27] AlSahman L, AlBagieh H, AlSahman R. Stress and salivary cortisol levels among temporomandibular disorders: a case-control study. Journal of Oral & Facial Pain and Headache. 2025; 39: 202–209.
[28] Eslami H, Azizi B, Katebi K, Hoseini Z. Association between temporomandibular joint disorders and salivary cortisol levels: a systematic review and meta-analysis. Shiraz E-Medical Journal. 2023; 24: e137608.
[29] Moffat SD, An Y, Resnick SM, Diamond MP, Ferrucci L. Longitudinal change in cortisol levels across the adult life span. The Journals of Gerontology: Series A. 2020; 75: 394–400.
[30] Stamou MI, Colling C, Dichtel LE. Adrenal aging and its effects on the stress response and immunosenescence. Maturitas. 2023; 168: 13–19.
[31] Whittaker J, Harris M. Low-carbohydrate diets and men’s cortisol and testosterone: systematic review and meta-analysis. Nutrition and Health. 2022; 28: 543–554.
[32] Ueno M. No significant difference in salivary cortisol response to the trier social stress test-online based on coffee consumption habits. BMC Psychology. 2024; 12: 483.
[33] De Nys L, Anderson K, Ofosu EF, Ryde GC, Connelly J, Whittaker AC. The effects of physical activity on cortisol and sleep: a systematic review and meta-analysis. Psychoneuroendocrinology. 2022; 143: 105843.
[34] Moyers SA, Hagger MS. Physical activity and cortisol regulation: a meta-analysis. Biological Psychology. 2023; 179: 108548.
[35] Lassale C, Lugon G, Hernáez Á, Frank P, Marrugat J, Ramos R, et al. Trajectories of antidepressant use and 6-year change in body weight: a prospective population-based cohort study. Frontiers in Psychiatry. 2024; 15: 1464898.
[36] Cakir M, Yalcin Ülker GM, Erdogan Ö. Prevalence and comparison of temporomandibular disorders according to Axis I in RDC/TMD and DC/TMD: a cross-sectional study. Quintessence International. 2025; 56: 238–247.
[37] Saini RS, Quadri SA, Mosaddad SA, Heboyan A. The relationship between psychological factors and temporomandibular disorders: a systematic review and meta-analysis. Head & Face Medicine. 2025; 21: 46.
Science Citation Index (SCI)
Science Citation Index Expanded (SCIE)
BIOSIS Previews
Scopus: CiteScore 3.1 (2024)
Cumulative Index to Nursing and Allied Health Literature (CINAHL)
Top