Chronic inflammation in polycystic ovary syndrome: A case–control study using multiple markers
Background: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and elevated risk of cardiovascular disease and diabetes. Chronic inflammation has been observed in PCOS in several studies but there is also opposing evidence and a dearth of research in Indians.
Objective: To estimate chronic inflammation in PCOS and find its relationship with appropriate anthropometric and biochemical parameters.
Materials and Methods: Chronic inflammation was assessed in 30 women with PCOS (Group A) and 30 healthy controls (Group B) with highly sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumour necrosis factor alpha (TNFα), and platelet microparticles (PMP). In group A, the relationship of chronic inflammation with insulin resistance, waist hip ratio (WHR) serum testosterone, and serum glutamate pyruvate transaminase (SGPT) were examined.
Results: In group A, the hsCRP, TNFα, and PMP were significantly elevated compared to group B. However, IL-6 level was similar between the groups. In group A, PMP showed a significant positive correlation with waist-hip ratio and serum testosterone. IL-6 showed a significant positive correlation with insulin sensitivity and significant negative correlation with insulin resistance and serum glutamate pyruvate transaminase.
Conclusion: PCOS is associated with chronic inflammation and PMP correlates positively with central adiposity and biochemical hyperandrogenism in women with PCOS.
Key words: Polycystic ovary syndrome, Inflammation, C-reactive protein, Interleukin-6, Tumor necrosis factor, Microparticles.
 Ding T, Hardiman PJ, Petersen I, Wang FF, Qu F, Baio G. The prevalence of polycystic ovary syndrome in reproductive-aged women of different ethnicity: A systematic review and meta-analysis. Oncotarget 2017; 8: 96351–96358.
 Torchen LC. Cardiometabolic risk in PCOS: More than a reproductive disorder. Curr Diab Rep 2017; 17: 137.
 Marshall JC, Dunaif A. Should all women with PCOS be treated for insulin resistance? Fertil Steril 2012; 97: 18–22.
 Ng NYH, Jiang G, Cheung LP, Zhang Y, Tam CHT, Luk AOY, et al. Progression of glucose intolerance and cardiometabolic risk factors over a decade in Chinese women with polycystic ovary syndrome: A case-control study. PLoS Med 2019; 16: e1002953.
 Randeva HS, Tan BK, Weickert MO, Lois K, Nestler JN, Sattar N, et al. Cardiometabolic aspects of the polycystic ovary syndrome. Endocr Rev 2012; 33: 812–841.
 Wild RA, Carmina E, Diamanti-Kandarakis E, Dokras A, Escobar-Morreale HF, Futterweit W, et al. Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: A consensus statement by the androgen excess and polycystic ovary syndrome (AE-PCOS) society. J Clin Endocrinol Metab 2010; 95: 2038–2049.
 Kamath DY, Xavier D, Sigamani A, Pais P. High sensitivity C-reactive protein (hsCRP) & cardiovascular disease: An Indian perspective. Indian J Med Res 2015; 142: 261–268.
 Lainampetch J, Panprathip P, Phosat C, Chumpathat N, Prangthip P, Soonthornworasiri N, et al. Association of tumor necrosis factor alpha, interleukin 6, and C-reactive protein with the risk of developing type 2 diabetes: A retrospective cohort study of rural thais. J Diabetes Res 2019; 2019: 905929.
 Zohmangaihi D, Sharma SB, Madhu SV. Adiponectin, IL-6 and hsCRP: Interplay of inflammation with obesity and type 2 diabetes in Indian population. J Diabetes Metab 2019; 10: 822.
 França CN, Izar MCdeO, do Amaral JB, Tegani DM, Fonseca FAH. Microparticles as potential biomarkers of cardiovascular disease. Arq Bras Cardiol 2015; 104: 169–174.
 Escobar-Morreale HF, Luque-Ramírez M, González F. Circulating inflammatory markers in polycystic ovary syndrome: A systematic review and meta analysis. Fertil Steril 2011; 95: 1048–1058.e1–e2.
 Kelly CC, Lyall H, Petrie JR, Gould GW, Connell JM, Sattar N. Low grade chronic inflammation in women with polycystic ovarian syndrome. J Clin Endocrinol Metab 2001; 86: 2453–2455.
 Thathapudi S, Kodati V, Erukkambattu J, Katragadda A, Addepally U, Hasan Q. Tumor necrosis factoralpha and polycystic ovarian syndrome: A clinical, biochemical, and molecular genetic study. Genet Test Mol Biomarkers 2014; 18: 605–609.
 Zafari Zangeneh F, Naghizadeh MM, Masoumi M. Polycystic ovary syndrome and circulating inflammatory markers. Int J Reprod Biomed 2017; 15: 375–382.
 Duleba AJ, Dokras A. Is PCOS an inflammatory process? Fertil Steril 2012; 97: 7–12.
 Barcellos CR, Rocha MP, Hayashida SA, Dantas WW, Yance VDRV, Marcondes JA. Obesity, but not polycystic ovary syndrome, affects circulating markers of low-grade inflammation in young women without major cardiovascular risk factors. Hormones 2015; 14: 251–257.
 González F, Nair KS, Daniels JK, Basal E, Schimke JM. Hyperandrogenism sensitizes mononuclear cells to promote glucose-induced inflammation in lean reproductive-age women. Am J Physiol Endocrinol Metab 2012; 302: e297–e306.
 Karoli R, Fatima J, Siddiqi Z, Vatsal P, Sultania AR, Maini S. Study of early atherosclerotic markers in women with polycystic ovarian syndrome. Indian J Endocrinol Metab 2012; 16: 1004–1008.
 Koiou E, Tziomalos K, Katsikis I, Kalaitzakis E, Kandaraki EA, Tsourdi EA, et al. Circulating plateletderived microparticles are elevated in women with polycystic ovary syndrome diagnosed with the 1990 criteria and correlate with serum testosterone levels. Eur J Endocrinol 2010; 165: 63–68.
 Koiou E, Tziomalos K, Katsikis I, Papadakis E, Kandaraki EA, Panidis D. Platelet-derived microparticles in overweight/obese women with the polycystic ovary syndrome. Gynecol Endocrinol 2013; 29: 250–253.
 Kim JW, Han JE, Kim YS, Won HJ, Yoon TK, Lee WS. High sensitivity C-reactive protein and its relationship with impaired glucose regulation in lean patients with polycystic ovary syndrome. Gynecol Endocrinol 2012; 28: 259–263.
 Aytan AN, Bastu E, Demiral I, Bulut H, Dogan M, Buyru F. Relationship between hyperandrogenism, obesity, inflammation and polycystic ovary syndrome. Gynecol Endocrinol 2016; 32: 709–713.
 Ramamoorthy S, Bhuvaneswari K. A cross-sectional study on the status of inflammatory markers in polycystic ovary syndrome (PCOS) in Indian population. Biomed Pharmacol J 2019; 12: 1975– 1983.
 Pawelczak M, Rosenthal J, Milla S, Liu YH, Shah B. Evaluation of the pro-inflammatory cytokine tumor necrosis factor-α in adolescents with polycystic ovary syndrome. J Pediatr Adolesc Gynecol 2014; 27: 356–359.
 Escobar-Morreale HF, Luque-Ramírez M, González F. Circulating inflammatory markers in polycystic ovary syndrome: A systematic review and metaanalysis. Fertil Steril 2011; 95: 1048–1058. e1–e2.
 Fulghesu AM, Sanna F, Uda S, Magnini R, Portoghese E, Batetta B. IL-6 serum levels and production is related to an altered immune response in polycystic ovary syndrome girls with insulin resistance. Mediators Inflamm 2011; 2011: 389317.
 Lin YS, Tsai SJ, Lin MW, Yang CT, Huang MF, Wu MH. Interleukin-6 as an early chronic inflammatory marker in polycystic ovary syndrome with insulin receptor substrate-2 polymorphism. Am J Reprod Immunol 2011; 66: 527–533.
 Matthews VB, Allen TL, Risis S, Chan MHS, Henstridge DC, Watson N, et al. Interleukin-6- deficient mice develop hepatic inflammation and systemic insulin resistance. Diabetologia 2010; 53: 2431–2441.
 Kamimura D, Ishihara K, Hirano T. IL-6 signal transduction and its physiological roles: The signal orchestration model. Rev Physiol Biochem Pharmacol 2003; 149: 1–38.