Comparative Analysis of Traditional and Emerging Salivary Biomarkers in Polycystic Ovary Syndrome Diagnosis Traditional vs Novel Biomarkers in PCOS
Article Sidebar
Main Article Content
Abstract
Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age globally, with a reported prevalence ranging from 10% to 20% depending on the diagnostic criteria used. This study designed to evaluate the differences in hormonal, metabolic, and inflammatory profiles, and to assess the diagnostic utility of non-invasive salivary cytokines (IL-6, TNF-α, IL-1β) in women with Polycystic Ovary Syndrome (PCOS). A case-control study was conducted on 100 women (50 PCOS and 50 controls). PCOS women were diagnosed based on the Rotterdam Criteria. Fasting blood and unstimulated saliva samples were collected. Biomarkers, including Total Testosterone, SHBG, FAI, HOMA-IR, and salivary IL-6, TNF-α, and IL-1β, were measured. Statistical analysis included Independent Samples t-test, Pearson's correlation, ROC curve analysis to determine diagnostic performance, and binary logistic regression to identify independent predictors. The PCOS group showed highly significant elevations (P<0.001) in all measured biomarkers compared to controls, with large effect sizes (Cohen's d > 1.3). Markedly, salivary IL-6, TNF-α, and IL-1β were substantially increased (d > 2.4). ROC analysis revealed exceptional diagnostic accuracy for the Free Androgen Index (FAI) (AUC=0.97) and the salivary cytokines, particularly salivary IL-1β (AUC=0.98) and salivary TNF-α (AUC=0.97). Binary logistic regression identified the FAI as the strongest independent predictor of PCOS (OR = 7.469, P=0.0121). In conclusion, the results of the current study showed that PCOS was strongly associated with a pronounced state of chronic low-grade inflammation, reliably reflected by salivary cytokines. The high diagnostic accuracy of salivary IL-1β and TNF-α suggests that non-invasive salivary analysis can serve as a highly accurate and patient-friendly tool for assessing the inflammatory component of PCOS, complementing the established role of the Free Androgen Index.
Article Details
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
The Journal of Medical and Oral Biosciences uses a Creative Commons Attribution (CC Attribution-ShareAlike 4.0) and its license of (CC BY-SA 4.0). This license allows the authors to hold ownership of the copyright of their articles.
Attribution-Share Alike 4.0 International License (CC BY-SA 4.0). 
Under the CC BY-SA 4.0 the authors are free to:
Share — copy and redistribute the material in any medium or format for any purpose, even commercially.
Adapt — remix, transform, and build upon the material for any purpose, even commercially.
The licensor cannot revoke these freedoms as long as you follow the license terms.
Under the following terms:
Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
ShareAlike — If you remix, transform, or build upon the material, you must distribute your contributions under the same license as the original.
No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
No use, distribution or reproduction is permitted which does not comply with these terms.
https://creativecommons.org/licenses/by-sa/4.0/
References
1. Farhana AA, Shi J. A Narrative Review on Global Epidemiology of PCOS and its Hormonal Management. SSR Inst Int J Life Sci. 2024;10(3):5516-5521. doi: 10.21276/SSR-IIJLS.2024.10.3.17.
2. Tammo O. Understanding Polycystic Ovary Syndrome: A Comprehensive Guide [Internet]. Obstetrics and Gynecology. IntechOpen; 2025. https://doi.org/10.5772/intechopen.1010597
3. Kakoly NS, Moran LJ, Teede HJ, Joham AE. Cardiometabolic risks in PCOS: a review of the current state of knowledge. Expert Rev Endocrinol Metab. 2019 Jan;14(1):23-33. doi: 10.1080/17446651.2019.1556094. PMID: 30556433.
4. Herman R, Sikonja J, Jensterle M, Janez A, Dolzan V. Insulin Metabolism in Polycystic Ovary Syndrome: Secretion, Signaling, and Clearance. Int J Mol Sci. 2023 Feb 5;24(4):3140. doi: 10.3390/ijms24043140. PMID: 36834549; PMCID: PMC9962893.
5. Zeng X, Xie YJ, Liu YT, Long SL, Mo ZC. Polycystic ovarian syndrome: correlation between hyperandrogenism, insulin resistance and obesity. Clin Chim Acta. 2020 Mar;502:214-221. doi: 10.1016/j.cca.2019.11.003. PMID: 31733195.
6. Rudnicka E, Suchta K, Grymowicz M, Calik-Ksepka A, Smolarczyk K, Duszewska AM, Smolarczyk R, Meczekalski B. Chronic low grade inflammation in pathogenesis of PCOS. Int J Mol Sci. 2021 Apr 6;22(7):3789. doi: 10.3390/ijms22073789. PMID: 33917519; PMCID: PMC8038770.
7. Azizova ZS, Musakhodzhayeva DA, Ruzimurodov NF, Olimova NI. Systemic relationships of inflammatory, hormonal, and metabolic markers in women with polycystic ovary syndrome. Russian Journal of Immunology. 2025;28(4):1055-1060. doi: 10.46235/1028-7221-17224-SRO.
8. Faloia E, Michetti G, De Robertis M, Luconi MP, Furlani G, Boscaro M. Inflammation as a link between obesity and metabolic syndrome. J Nutr Metab. 2012;2012:476380. doi: 10.1155/2012/476380. PMID: 22523672; PMCID: PMC3317136.
9. Viardot-Foucault V. Enhancing the accuracy of polycystic ovary syndrome diagnosis. Ann Acad Med Singap. 2023 Dec 28;52(12):647-648. doi: 10.47102/annals-acadmedsg.2023397.
10. Ryznar R, Andrews N. Salivary Neuropeptides and Cytokines: Indicators of Stress and Resilience. In: Aitken-Saavedra J, Rojas-Alcayaga G, Braz-Silva PH, editors. Salivary Analysis - Biomarkers, Clinical Applications, and Emerging Technologies. London: IntechOpen; 2025. doi: 10.5772/intechopen.1010391.
11. Dagli N, Haque M, Kumar S. A Bibliometric Analysis of Clinical Trials on Salivary Biomarkers for Mental Health (2003-2024). Cureus. 2024 Jul 16;16(7):e64635. doi: 10.7759/cureus.64635. PMID: 39021745; PMCID: PMC11253590.
12. Yoshizawa JM, Schafer CA, Schafer JJ, Farrell JJ, Paster BJ, Wong DT. Salivary biomarkers: toward future clinical and diagnostic utilities. Clin Microbiol Rev. 2013 Oct;26(4):781-791. doi: 10.1128/CMR.00021-13. PMID: 24092855; PMCID: PMC3811231.
13. Panda S, Jyothi K, Konar L, Hussain Z. Unmasking the Overlooked Symptoms of PCOS: Navigating Ovulatory Dysfunction, Menstrual Disorders, and Acne. In: Wang Z, editor. Understanding Polycystic Ovary Syndrome - Symptoms, Diagnosis, and Treatment Options. IntechOpen; 2025. doi: 10.5772/intechopen.1011570.
14. Mortazavi H, Yousefi-Koma AA, Yousefi-Koma H. Extensive comparison of salivary collection, transportation, preparation, and storage methods: a systematic review. BMC Oral Health. 2024 Feb 2;24(1):168. doi: 10.1186/s12903-024-03902-w. PMID: 38308289; PMCID: PMC10837873.
15. Sanke S, Chander R, Garg T, Jain A. Free Androgen Index (FAI): Marker of Premature Androgenetic Alopecia in Men. J Microb Biochem Technol. 2016 Feb 24;8(2):97-99. doi: 10.4172/1948-5948.1000269.
16. Orbay E, Demiral BH, Tüzün S, Öner C. The association of insulin resistance with body mass index and body fat percentages in non-diabetic obese women. Anatol J Fam Med. 2018;1(1):13-16. doi: 10.5505/anatoljfm.2018.88598.
17. Deng H, Chen Y, Xing J, Zhang N, Xu L. Systematic low-grade chronic inflammation and intrinsic mechanisms in polycystic ovary syndrome. Front Immunol. 2024;15:1470283. doi: 10.3389/fimmu.2024.1470283. PMID: 39749338; PMCID: PMC11693511.
18. Çelik E, Kara SS, Çevik Ö. The potential use of saliva as a biofluid for systemic inflammatory response monitoring in children with pneumonia. Indian J Pediatr. 2022 May;89(5):477-483. doi: 10.1007/s12098-021-03973-5. PMID: 34595601.
19. Shakeeb N, Varkey P, Hynse A, Ajit A. Saliva as a Potential Specimen to Monitor IL-6, TNF-α and IL-10 in COVID-19 Patients. Inflammation. 2022 Dec;45(6):2368-2374. doi: 10.1007/s10753-022-01698-x. PMID: 35676607; PMCID: PMC9177134.
20. Velez LM, Seldin M, Motta AB. Inflammation and reproductive function in women with polycystic ovary syndrome. Biol Reprod. 2021 Jun 4;104(6):1205-17. doi: 10.1093/biolre/ioab050. PMID: 33739372; PMCID: PMC8785941.
21. Zapała B, Marszalec P, Piwowar M, Chmura O, Milewicz T. Reduction in the free androgen index in overweight women after sixty days of a low glycemic diet. Exp Clin Endocrinol Diabetes. 2024 Jan 18;132(1):6-14. doi: 10.1055/a-2201-8618. PMID: 38237611; PMCID: PMC10796197.