Association of Oxidative Stress Biomarkers with Polycystic Ovary Syndrome (PCOS) and Its Metabolic Outcomes, Including Insulin Resistance and Dyslipidemia: A Systematic Review
Oxidative Stress Biomarkers with PCOS: Insulin Resistance and Dyslipidemia
DOI:
https://doi.org/10.54393/pjhs.v6i11.3504Keywords:
Polycystic Ovary Syndrome, Oxidative Stress, Malondialdehyde, Total Antioxidant Capacity, Insulin Resistance, Metabolic SyndromeAbstract
Polycystic ovary syndrome (PCOS) is a common endocrine metabolic disorder characterized by hyperandrogenism, ovulatory dysfunction, and insulin resistance. Increasing evidence suggests that oxidative stress (OS) contributes to its metabolic and reproductive complications. Objectives: To systematically review primary studies evaluating oxidative stress biomarkers in PCOS and their associations with metabolic outcomes. Methods: A comprehensive search was conducted in PubMed, Scopus, and Cochrane Library up to April 2024, following PRISMA 2020 guidelines. Eligible studies included case–control and cross-sectional designs reporting quantitative OS biomarker data in PCOS versus controls. Quality and risk of bias were assessed using the Newcastle Ottawa Scale (NOS). Results: Fifteen studies (2014–2024) involving over 1,000 participants were included. Malondialdehyde (MDA) was elevated in nearly all studies, indicating enhanced lipid peroxidation. Total antioxidant capacity (TAC/FRAP) and enzymatic antioxidants (SOD, CAT) were consistently reduced, while non-enzymatic antioxidants (GSH, vitamins A/C/E) were also lower. PON1 activity and sRAGE levels decreased, and 8-isoprostane in follicular fluid correlated with poorer oocyte quality. OS markers were positively associated with BMI, insulin resistance, and dyslipidemia. Five studies were rated low risk and ten moderate risk by NOS criteria. Conclusions: PCOS is characterized by increased oxidative stress and reduced antioxidant defense, closely linked to metabolic severity. Incorporating OS biomarkers into clinical evaluation and exploring phenotype-specific antioxidant interventions may improve metabolic and reproductive outcomes. Future longitudinal studies should standardize biomarker measurement to strengthen clinical applicability.
References
Bahreiny SS, Ahangarpour A, Saki N, Dabbagh MR, Ebrahimi R, Mahdizade AH et al. Association of Free Radical Product and Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis. Reproductive Sciences. 2024 Jun; 31(6): 1486-95. doi: 10.1007/s43032-023-01447-x. DOI: https://doi.org/10.1007/s43032-023-01447-x
Singh I, Moar K, Maurya PK. Diagnostic and Prognostic Biomarkers in Polycystic Ovary Syndrome. Clinica Chimica Acta. 2025 Jun: 120425. doi: 10.1016/j.cca.2025.120425. DOI: https://doi.org/10.1016/j.cca.2025.120425
Duică F, Dănilă CA, Boboc AE, Antoniadis P, Condrat CE, Onciul S et al. Impact of Increased Oxidative Stress on Cardiovascular Diseases in Women with Polycystic Ovary Syndrome. Frontiers in Endocrinology. 2021 Feb; 12: 614679. doi: 10.3389/fendo.2021.614679. DOI: https://doi.org/10.3389/fendo.2021.614679
Camp OG, Moussa DN, Hsu R, Awonuga AO, Abu-Soud HM. The Interplay Between Oxidative Stress, Zinc, and Metabolic Dysfunction in Polycystic Ovarian Syndrome. Molecular and Cellular Biochemistry. 2025 Apr; 480(4): 2015-23. doi: 10.1007/s11010-024-05113-x. DOI: https://doi.org/10.1007/s11010-024-05113-x
Fatima Q, Amin S, Kawa IA, Jeelani H, Manzoor S, Rizvi SM et al. Evaluation of Antioxidant Defense Markers in Relation to Hormonal and Insulin Parameters in Women with Polycystic Ovary Syndrome (PCOS): A Case-Control Study. Diabetes & Metabolic Syndrome: Clinical Research and Reviews. 2019 May; 13(3): 1957-61. doi: 10.1016/j.dsx.2019.04.032. DOI: https://doi.org/10.1016/j.dsx.2019.04.032
Gkantzos A, Kalogiannis S, Deda O. The Role of Aromatic Amino Acids in Polycystic Ovary Syndrome through Patients’ Blood Metabolic Profiling: A Systematic Review of the Past Five Years. Journal of Proteome Research. 2025 Apr; 24(5): 2208-21. doi: 10.1021/acs.jproteome.4c00937. DOI: https://doi.org/10.1021/acs.jproteome.4c00937
Yan H, Wang L, Zhang G, Li N, Zhao Y, Liu J et al. Oxidative Stress and Energy Metabolism Abnormalities in Polycystic Ovary Syndrome: From Mechanisms to Therapeutic Strategies. Reproductive Biology and Endocrinology. 2024 Dec; 22(1): 159. doi: 10.1186/s12958-024-01337-0. DOI: https://doi.org/10.1186/s12958-024-01337-0
Padder KA, Jahan N, Yousuf MA, Shah IA, Bhat GA, Khurshid R et al. Deciphering the Interplay Between Oxidative Stress and Inflammation in Polycystic Ovary Syndrome: Outcome of A Case-Control Study. Journal of Ovarian Research. 2025 Aug; 18(1): 196. doi: 10.1186/s13048-025-01734-y. DOI: https://doi.org/10.1186/s13048-025-01734-y
Gao Y, Zou Y, Wu G, Zheng L. Oxidative Stress and Mitochondrial Dysfunction of Granulosa Cells in Polycystic Ovarian Syndrome. Frontiers in Medicine. 2023 Jun; 10: 1193749. doi: 10.3389/fmed.2023.1193749. DOI: https://doi.org/10.3389/fmed.2023.1193749
Santander N, Figueroa EG, González-Candia A, Maliqueo M, Echiburú B, Crisosto N et al. Oxidative Stress in Polycystic Ovary Syndrome: Impact of Combined Oral Contraceptives. Antioxidants. 2024 Sep; 13(10): 1168. doi: 10.3390/antiox13101168. DOI: https://doi.org/10.3390/antiox13101168
Kumari D, Kumar M, Upadhyay AD, Malhotra N, Mahey R, Dadhwal V et al. Unveiling Therapeutic Potential of Yoga Mitigating Oxidative Stress and Mitochondrial Dysfunction in PCOS: A Randomized Controlled Trial. International Journal of Yoga. 2025 Jan; 18(1): 45-57. doi: 10.4103/ijoy.ijoy_212_24. DOI: https://doi.org/10.4103/ijoy.ijoy_212_24
Nasiri M, Monazzami A, Alavimilani S, Asemi Z. Modulation of Hormonal, Metabolic, Inflammatory and Oxidative Stress Biomarkers in Women with Polycystic Ovary Syndrome Following Combined (Resistant and Endurance) Training: A Randomized Controlled Trail. BioMed Central Endocrine Disorders. 2025 Jan; 25(1): 1. doi: 10.1186/s12902-024-01793-0. DOI: https://doi.org/10.1186/s12902-024-01793-0
Azim SS, Haque Z, Khan S, Hasan JA, Zaheer S, Parveen S. Oxidative Stress in Polycystic Ovary Syndrome: A Case-Control Study. The Journal of the Pakistan Medical Association. 2024 Feb; 74(1 (Supple-2)): S2-7. doi: 10.47391/JPMA-DUHS-S02. DOI: https://doi.org/10.47391/JPMA-DUHS-S02
Zaki M, Sherity SY, Metkees M, Salem S, Elnahas T, Salama E et al. Total Antioxidant Capacity Status in Non-Obese Adolescent Females with PCOS: A Cross-Section Study. Middle East Fertility Society Journal. 2024 Nov; 29(1): 51. doi: 10.1186/s43043-024-00209-2. DOI: https://doi.org/10.1186/s43043-024-00209-2
Enechukwu CI, Onuegbu AJ, Olisekodiaka MJ, Eleje GU, Ikechebelu JI, Ugboaja JO et al. Oxidative Stress Markers and Lipid Profiles of Patients with Polycystic Ovary Syndrome in A Nigerian Tertiary Hospital. Obstetrics and Gynecology Science. 2019 Aug; 62(5): 335-43. doi: 10.5468/ogs.2019.62.5.335. DOI: https://doi.org/10.5468/ogs.2019.62.5.335
Nawrocka-Rutkowska J, Szydłowska I, Jakubowska K, Olszewska M, Chlubek D, Rył A et al. Assessment of the Parameters of Oxidative Stress Depending on the Metabolic and Anthropometric Status Indicators in Women with PCOS. Life. 2022 Jan; 12(2): 225. doi: 10.3390/life12020225. DOI: https://doi.org/10.3390/life12020225
Gurbuz T, Tosun SA, Cebi A, Gokmen O, Usta M. Investigating Fetuin-A and Paraoxonase-1 Activity as Markers in Polycystic Ovary Syndrome Based on Body Mass Index: A Prospective Case-Control Study. Cureus. 2021 Oct; 13(10). doi: 10.7759/cureus.18553. DOI: https://doi.org/10.7759/cureus.18553
Sulaiman MA, Al-Farsi YM, Al-Khaduri MM, Saleh J, Waly MI. Polycystic Ovarian Syndrome Is Linked to Increased Oxidative Stress in Omani Women. International Journal of Women's Health. 2018 Nov: 763-71. doi: 10.2147/IJWH.S166461. DOI: https://doi.org/10.2147/IJWH.S166461
Alfeel AH, Hussein SE, Yousif TE, Babker AM, Altoum AA, Mohamed AN et al. Association Between Oxidative Stress, Antioxidant Enzymes, and Homocysteine in Patients with Polycystic Ovary Syndrome. European Review for Medical and Pharmacological Sciences. 2023 Nov; 27(21): 10631-41.
Gongadashetti K, Gupta P, Dada R, Malhotra N. Follicular Fluid Oxidative Stress Biomarkers and ART Outcomes in PCOS Women Undergoing in Vitro Fertilization: A Cross-Sectional Study. International Journal of Reproductive Biomedicine. 2021 Jun; 19(5): 449. doi: 10.18502/ijrm.v19i5.9254. DOI: https://doi.org/10.18502/ijrm.v19i5.9254
Niepsuj J, Franik G, Madej P, Piwowar A, Bizoń A. Evaluation of Pro/Antioxidant Imbalance in Blood of Women with Polycystic Ovary Syndrome Based on Determination of Oxidized Low-Density Lipoproteins and Ferric Reducing Ability of Plasma Values. Biomedicines. 2022 Jun; 10(7): 1564. doi: 10.3390/biomedicines10071564. DOI: https://doi.org/10.3390/biomedicines10071564
Sen B, Gonultas S, Albayrak C, Temur S, Acar I, Ozkan BN et al. Evaluation of Oxidative Stress and Inflammation in Patients with Polycystic Ovary Syndrome. Obstetrics and Gynecology Science. 2024 May; 67(4): 414-20. doi: 10.5468/ogs.24031. DOI: https://doi.org/10.5468/ogs.24031
Emami N, Alizadeh A, Maleki-Hajiagha A, Dizavi A, Vesali S, Moini A. Serum and Follicular Fluid Levels of Soluble Receptor for Advanced Glycation End-Products in Women with and without Polycystic Ovary Syndrome. Journal of Ovarian Research. 2023 Jun; 16(1): 127. doi: 10.1186/s13048-023-01224-z. DOI: https://doi.org/10.1186/s13048-023-01224-z
Onal M and Agar M. Follicular Fluid Redox Balance and DNA Damage According to PCOS Phenotype. European Review for Medical and Pharmacological Sciences. 2023 Jun; 27(12).
Deepika ML, Nalini S, Maruthi G, Ramchander V, Ranjith K, Latha KP, Rani VU, Jahan P. Analysis of Oxidative Stress Status Through MN Test and Serum MDA Levels in PCOS Women. Pakistan Journal of Biological Sciences. 2014 Apr; 17(4): 574-7. doi: 10.3923/pjbs.2014.574.577. DOI: https://doi.org/10.3923/pjbs.2014.574.577
Mahmud AA, Anu UH, Foysal KA, Hasan M, Sazib SM, Ragib AA et al. Elevated Serum Malondialdehyde (MDA), Insulin, Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), and Thyroid-Stimulating Hormone (TSH), and Reduced Antioxidant Vitamins in Polycystic Ovarian Syndrome Patients. Narra J. 2022 Apr; 2(1): e56. doi: 10.52225/narra.v2i1.56. DOI: https://doi.org/10.52225/narra.v2i1.56
Sharma H, Yang H, Sharma N, An SS. Trachyspermum ammi Bioactives Promote Neuroprotection by Inhibiting Acetylcholinesterase, Aβ-Oligomerization/Fibrilization, and Mitigating Oxidative Stress in Vitro. Antioxidants. 2023 Dec; 13(1): 9. doi: 10.3390/antiox13010009. DOI: https://doi.org/10.3390/antiox13010009
Abudawood M. Exploring the Role of Rare Earth Elements (Praseodymium, Samarium, Lanthanum, and Terbium) and Oxidative Stress in Polycystic Ovary Syndrome: A Case-Control Study. Human and Experimental Toxicology. 2025 May; 44: 09603271251342280. doi: 10.1177/09603271251342280. DOI: https://doi.org/10.1177/09603271251342280
Ardehjani NA, Agha-Hosseini M, Nashtaei MS, Khodarahmian M, Shabani M, Jabarpour M et al. Resveratrol Ameliorates Mitochondrial Biogenesis nd Reproductive Outcomes Iin Women with Polycystic Ovary Syndrome Undergoing Assisted Reproduction: A Randomized, Triple-Blind, Placebo-Controlled Clinical Trial. Journal of Ovarian Research. 2024 Jul; 17(1): 143. doi: 10.1186/s13048-024-01470-9. DOI: https://doi.org/10.1186/s13048-024-01470-9
Banal-Silao MJ, Fpogs F, Fpsge F. The Role of Growth Hormone in Improving Oocyte Quality in IVF Cycles. Philippine Journal of Reproductive Endocrinology and Infertility. 2023: 12-23.
Pereira VB, Lago CA, Almeida RD, Barbirato DD, Vasconcelos BC. Biological and Cellular Properties of Advanced Platelet-Rich Fibrin (A-PRF) Compared to Other Platelet Concentrates: Systematic Review and Meta-Analysis. International Journal of Molecular Sciences. 2023 Dec; 25(1): 482. doi: 10.3390/ijms25010482. DOI: https://doi.org/10.3390/ijms25010482
Ildarabadi A, Vahid-Dastjerdi M, Ghorbanpour M, Mousavi A, Meshkani M, Yekaninejad M et al. Effects of Green Coffee Supplementation on Paraoxonase-1 Activity and Malondialdehyde Levels in Iranian Women with Polycystic Ovary Syndrome: A Randomized Clinical Trial. Osong Public Health and Research Perspectives. 2024 Nov; 15(6): 521. doi: 10.24171/j.phrp.2024.0187. DOI: https://doi.org/10.24171/j.phrp.2024.0187
Daraghmeh DN, Salameh S, Zahdeh M, Ghanem R, Karaman R. Exploring the Effects of Oxidative Stress on Female Reproductive Function: The Role of Antioxidant Supplementation. Current Drug Metabolism. 2025. doi: 10.2174/0113892002357565250604075932. DOI: https://doi.org/10.2174/0113892002357565250604075932
Ibrahim EA, Elhardallo WA, Ahmed KA, Omer ME, Eljack MM. Outcome of Topiramate in Migraine Prophylaxis. Annals of Medicine and Surgery. 2023 Mar; 85(3): 382-6. doi: 10.1097/MS9.0000000000000093. DOI: https://doi.org/10.1097/MS9.0000000000000093
Mizgier M, Jarząbek-Bielecka G, Wendland N, Jodłowska-Siewert E, Nowicki M, Brożek A et al. Relation Between Inflammation, Oxidative Stress, and Macronutrient Intakes in Normal and Excessive Body Weight Adolescent Girls with Clinical Features of Polycystic Ovary Syndrome. Nutrients. 2021 Mar; 13(3): 896. doi: 10.3390/nu13030896. DOI: https://doi.org/10.3390/nu13030896
Song Y, Cai Q, Wang S, Li L, Wang Y, Zou S et al. The Ameliorative Effect and Mechanisms of Ruditapes Philippinarum Bioactive Peptides on Obesity and Hyperlipidemia Induced by A High-Fat Diet in Mice. Nutrients. 2022 Nov; 14(23): 5066. doi: 10.3390/nu14235066. DOI: https://doi.org/10.3390/nu14235066
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