Chronic low-grade inflammation – a key factor in the pathogenesis of polycystic ovary syndrome
Keywords:
chronic low-grade inflammation, cytokines, hematological indices, insulin resistance, polycystic ovary syndromeAbstract
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, with a global prevalence ranging between 8% and 13%, depending on the diagnostic criteria used. The NIH (1990), Rotterdam (2003), and AE-PCOS (2006) criteria differ in the included phenotypic features, leading to variability in prevalence rates and clinical presentation across different populations and regions. The Rotterdam criteria are the most widely applied, requiring the presence of at least two of the following three features: hyperandrogenism, oligo-/amenorrhea, and polycystic ovarian morphology. PCOS is associated not only with reproductive dysfunction, but also with an increased risk of insulin resistance, type 2 diabetes mellitus, and cardiovascular disease. The present review aims to summarize the role of chronic low-grade inflammation in the pathogenesis of PCOS. Factors modulating the inflammatory response are discussed, along with the potential of integrated hematological indices as easily accessible biomarkers of systemic inflammation.
References
Begum G, Almashaikhi N, Albalushi M, et al. Prevalence of polycystic ovary syndrome (PCOS) and its associated risk factors among medical students in two countries. Int J Environ Res Public Health. 2024;21(9):1165.
World Health Organization. Polycystic ovary syndrome [Internet]. Geneva: WHO; 2023 Jun 8 [cited 2024 Jun 1]. Available from: https://www.who.int
Stener-Victorin E, Teede H, Norman R, et al. Polycystic ovary syndrome. Nat Rev Dis Primers. 2024;10(1):27.
Christ JP, Cedars MI. Current guidelines for diagnosing polycystic ovary syndrome. Diagnostics (Basel). 2023;13(6):1113.
Baba T. Polycystic ovary syndrome: criteria, phenotypes and clinical heterogeneity. Reprod Med Biol. 2025;24:e12630.
International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 [Internet]. Melbourne: Monash University; 2023.
Elhassan YS, Hawley JM, Cussen L, et al. Society for Endocrinology clinical practice guideline for the evaluation of androgen excess in women. Endocr Connect. 2022;11(10):e22030.
Hemalatha M, Subashini S, Sharma P. Polycystic ovarian syndrome, aetiology, pathophysiology, current management and future therapeutics with emphasis on adolescent girls. Indian J Obstet Gynecol Res. 2026;13(1):26 –31.
Bozdag G, Mumusoglu S, Zengin D, et al. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod. 2016;31(12):2841-2855.
Dubey P, Reddy S, Sharma K, et al. Polycystic ovary syndrome, insulin resistance, and cardiovascular disease. Curr Cardiol Rep. 024;26(6):483–495.
Zheng L, Xu X, Zhou J, et al. The burden of polycystic ovary syndrome–related infertility in 204 countries and territories, 1990-2021: an analysis of the Global Burden of Disease Study 2021. Front Endocrinol (Lausanne). 2025;16:1559246.
Keeratibharat P, Sophonsritsuk A, Saipanish R, et al. Prevalence of depression and anxiety in women with polycystic ovary syndrome (PCOS) and associated factors in a quaternary hospital in Thailand: a cross-sectional study. BMC Psychiatry. 2024;24:760.
Deng H, Chen Y, Xing J, et al. Systemic low-grade chronic inflammation and intrinsic mechanisms in polycystic ovary syndrome. Front Immunol. 2024;15:1504358.
Cifuentes M, Verdejo HE, Castro PF, et al. Low-grade chronic inflammation: a shared mechanism for chronic diseases. Physiology (Bethesda). 2025;40(1):4–25.
Van de Vyver M. Immunology of chronic low-grade inflammation: relationship with metabolic function. J Endocrinol. 2023;257(1):e220271.
Колева ДИ, Орбецова ММ, Няголова ПВ, Митков МД. Индекси на инсулинова чувствителност/резистентност при жени с метаболитен синдром и поликистозен овариален синдром. Ендокринология. 2016;21(2):9–10.
Shabbir S, Khurram E, Moorthi VS, et al. The interplay between androgens and the immune response in polycystic ovary syndrome. J Transl Med. 2023;21:259.
He C, Lin Z, Robb SW, et al. Macrophage polarization in polycystic ovary syndrome. Reprod Sci. 2020;27(6):1159 –1167.
Ji Y, Li X, Yao X, et al. Macrophage polarization: molecular mechanisms, disease implications, and targeted therapeutic strategies. Front Immunol. 2025;16:1732718.
Yu X, Li Z. Macrophages, chronic inflammation, and insulin resistance. Cells. 2023;11(19):3001.
Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997;18(6):774-800.
White MF. IRS proteins and the common path to diabetes. Am J Physiol Endocrinol Metab. 2002;283(3):E413-E422.
Book CB, Dunaif A. Selective insulin resistance in the polycystic ovary syndrome. J Clin Endocrinol Metab. 1999;84(9):3110-3116.
Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev. 2012;33(6):981-1030.
Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259(5091):87-91.
Zhang L, Rodriguez H, Ohno S, et al. Serine phosphorylation of human P450c17 increases 17,20-lyase activity: implications for androgen excess in PCOS. Proc Natl Acad Sci U S A. 1995;92(23):10619-10623.
Gao X, Zhang Z, Huang Y, et al. Mitochondrial dysfunction and oxidative stress in granulosa cells from women with polycystic ovary syndrome. J Ovarian Res. 2023;16:45.
Li Y, Wang F, Zhao Y, et al. Oxidative stress impairs oocyte and granulosa cell quality in polycystic ovary syndrome: mechanistic insights. Reprod Biol Endocrinol. 2023;21:102.
Chen H, Liu M, Zhang J, et al. The role of oxidative stress in ovarian follicular development and oocyte quality in PCOS. Front Endocrinol (Lausanne). 2023;14:115678.
Li H, Zhang Y, Wang X, et al. Association between oxidative stress biomarkers and insulin resistance in women with PCOS: a systematic review and meta-analysis. Clin Endocrinol (Oxf). 2022;96(5):675-686.
Ding T, Hardiman PJ, Petersen I, et al. Oxidative stress and protein oxidation biomarkers in women with PCOS. Reprod Sci. 2021;28(11):3072-3083.
Sabry D, Al-Ghamdi A, Al-Malki A, et al. Evaluation of oxidative stress in women with PCOS and correlation with metabolic and hormonal parameters. J Obstet Gynaecol Res. 2022;48(2):393-402.
Cao Y, Liu H, Yi J, et al. Role of inflammation and oxidative stress in PCOS: updates and perspectives. Biomed Pharmacother. 2023;154:113637.
Chen Z, Tian R, She Z, et al. Inflammatory pathways linking metabolic dysfunction and reproductive disorders in PCOS. Front Endocrinol (Lausanne). 2023;14:1151246.
Azziz R, Carmina E, Chen Z, et al. Polycystic ovary syndrome: pathophysiology and emerging concepts on oxidative stress and inflammation. Endocr Rev. 2022;43(2):345-390.
Chamanara S, Rameshbabu S, Mei S, et al. Inhibition of NLRP3 inflammasome: a potential mechanistic therapeutic target in polycystic ovary syndrome. J Biochem Mol Toxicol. 2023;38(1):e23592.
Wang TH, Liu X, Zhang Y, et al. NLRP3 inflammasome in gynecologic inflammatory diseases: mechanisms and therapeutic perspectives. J Inflamm Res. 2025;18:14097-14112.
Xu G, Li Y, Chen X, et al. NSUN7-mediated regulation of NLRP3 inflammasome promotes granulosa cell pyroptosis in PCOS. Sci Rep. 2025;15:35145.
Lorestani S, Jalilian N, Moini A, et al. Association of NLRP3 gene polymorphisms with polycystic ovary syndrome susceptibility and metabolic parameters. J Ovarian Res. 2022;15(1):114.
González F. Chronic low-grade inflammation in polycystic ovary syndrome: is there a genetic basis for a metabolic disease? Eur J Endocrinol. 2012;167(4):447-457.
Rudnicka E, Kunicki M, Suchta K, et al. Inflammatory markers in women with polycystic ovary syndrome. Biomed Res Int. 2020;2020:4092470.
Vedavathi V, Veerabhadra Goud GK, Patil SV, et al. Neutrophilto-lymphocyte ratio and platelet-to-lymphocyte ratio are useful markers of inflammation in polycystic ovary syndrome? Asian J Med Sci. 2023;14(6):99-103.
Wang Y, Fu X, Xu J, et al. Systemic inflammation in polycystic ovary syndrome: a meta-analysis. J Clin Endocrinol Metab. 2011;96(3):E412-E420.
Taşkömür E, Yıldırım F, Kılıç F, et al. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with polycystic ovary syndrome. Cureus. 2022;14(12):e32789.
Ozkan H, Ozkan M, Dayanan R, et al. Inflammatory status and clinical phenotypes of polycystic ovary syndrome: role of NLR, SII, SIRI and AISI. BMC Womens Health. 2025;25(1):463.
Demirel F, Arikan I. Association between polycystic ovary syndrome and systemic immune inflammation index and other inflammation markers: a case-control study. J Obstet Gynaecol. 2025;25(3):79-86.
Cakir I, Cakir N. Immune-inflammation markers are related to hormone levels in polycystic ovary syndrome: a case-control study. BMC Endocr Disord. 2025;25(1):274.
Bansal B, Kishore AT, Sharma R, et al. Inflammatory markers in polycystic ovary syndrome and meta-analysis of interleukin-6. Cureus. 2025;17:e12082375.
Escobar-Morreale HF, Luque-Ramírez M, González F, et al. Circulating inflammatory markers in polycystic ovary syndrome: evidence from recent studies and clinical implications. Endocr Rev. 2023;44(6):1123-1145.
Kalyan S, Goshtesabi A, Sarray S, et al. Assessing C reactive protein/albumin ratio as a new biomarker for polycystic ovary syndrome: a case-control study. BMJ Open. 2018;8:e021860.
Dinarello CA. Cytokines as mediators of inflammation. J Allergy Clin Immunol. 2018;141(2):S5-S8.
Deng H, Zhang Y, Li J, et al. Systemic low-grade chronic inflammation and immune dysregulation in polycystic ovary syndrome. Front Immunol. 2024;15:1470283.
Dutta S, Sengupta P, Rao S, et al. Targeting polycystic ovary syndrome (PCOS) pathophysiology with flavonoids: from adipokine-cytokine crosstalk to insulin resistance and reproductive dysfunctions. Pharmaceuticals. 2025;18(10):1575.
Kaur P, Kaur K, Kaur R. Role of TNF-α and IL-6 polymorphisms in polycystic ovary syndrome. Int J Reprod Contracept Obstet Gynecol. 2024;13(4):963-970.
Banerjee S, Cooney L, Stanic A. Immune dysfunction in polycystic ovary syndrome. ImmunoHorizons. 2023;7(5):323-332.
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