{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:58:40Z","timestamp":1787662720793,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T00:00:00Z","timestamp":1727308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ANID FONDECYT","award":["F11201337"],"award-info":[{"award-number":["F11201337"]}]},{"name":"ANID FONDECYT","award":["11240017"],"award-info":[{"award-number":["11240017"]}]},{"name":"ANID FONDECYT","award":["1241626"],"award-info":[{"award-number":["1241626"]}]},{"name":"ANID FONDECYT","award":["F1210261"],"award-info":[{"award-number":["F1210261"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Polycystic Ovary Syndrome (PCOS) is a complex hormonal disorder that is associated with heightened metabolic risks. While oxidative stress (OS) is known to play a role in PCOS, the precise nature of the relationship between PCOS and increased OS remains not entirely understood. Combined oral contraceptives (COCs) are the first-line treatment to regulate menstrual cycles and androgen levels, but their impact on oxidative stress requires further study. We conducted a transcriptomic analysis using RNAseq and assessed the levels of various oxidative stress (OS) markers in serum samples from women with PCOS and controls and whether they were using combined oral contraceptives (COCs), including enzymatic activities, FRAP, and 8-isoprostane (8-iso). A total of 359 genes were differentially expressed in women with PCOS compared to control women. Genes differentially expressed were enriched in functions related to inflammation and, interestingly, oxidative stress response. In controls, 8-iso levels were increased in women using COCs, whereas in women with PCOS, 8-iso levels were reduced in those using oral contraceptives (191.1 \u00b1 97 vs. 26.4 \u00b1 21 pg\/mL, p: &lt;0.0001). Correlation analyses showed a trend for a negative correlation between 8-iso and Ferriman score in women with PCOS consuming COCs (r = \u22120.86, p = 0.06) and a negative correlation between GSH and hyperandrogenism in women with PCOS (r = \u22120.89, p = 0.01). These results reveal the presence of lipid peroxidation in women with PCOS, which was modified by the use of COCs, providing new insights into the pathophysiology of PCOS in the Chilean population.<\/jats:p>","DOI":"10.3390\/antiox13101168","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T04:05:46Z","timestamp":1727323546000},"page":"1168","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Oxidative Stress in Polycystic Ovary Syndrome: Impact of Combined Oral Contraceptives"],"prefix":"10.3390","volume":"13","author":[{"given":"Nicol\u00e1s","family":"Santander","sequence":"first","affiliation":[{"name":"Health Sciences Institute, Universidad de O\u2019Higgins, Rancagua 282000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1316-738X","authenticated-orcid":false,"given":"Esteban G.","family":"Figueroa","sequence":"additional","affiliation":[{"name":"Health Sciences Institute, Universidad de O\u2019Higgins, Rancagua 282000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8429-367X","authenticated-orcid":false,"given":"Alejandro","family":"Gonz\u00e1lez-Candia","sequence":"additional","affiliation":[{"name":"Health Sciences Institute, Universidad de O\u2019Higgins, Rancagua 282000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3872-0217","authenticated-orcid":false,"given":"Manuel","family":"Maliqueo","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Metabolism, Department of Internal Medicine, West Division, Faculty of Medicine, Universidad de Chile, Santiago 8350499, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6535-3104","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Echibur\u00fa","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Metabolism, Department of Internal Medicine, West Division, Faculty of Medicine, Universidad de Chile, Santiago 8350499, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9248-0264","authenticated-orcid":false,"given":"Nicol\u00e1s","family":"Crisosto","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Metabolism, Department of Internal Medicine, West Division, Faculty of Medicine, Universidad de Chile, Santiago 8350499, Chile"},{"name":"Endocrinology Endocrinology Unit, Department of Medicine, Cl\u00ednica Alemana de Santiago, Faculty of Medicine, Universidad del Desarrollo, Santiago 7650568, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisca","family":"Salas-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Health Sciences Institute, Universidad de O\u2019Higgins, Rancagua 282000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/S2213-8587(22)00163-2","article-title":"Polycystic Ovary Syndrome","volume":"10","author":"Joham","year":"2022","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/nrendo.2015.230","article-title":"New Insights into the Genetics of Polycystic Ovary Syndrome","volume":"12","author":"Azziz","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Christ, J.P., and Cedars, M.I. (2023). Current Guidelines for Diagnosing PCOS. Diagnostics, 13.","DOI":"10.3390\/diagnostics13061113"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1093\/humupd\/dmq001","article-title":"Impaired Glucose Tolerance, Type 2 Diabetes and Metabolic Syndrome in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis","volume":"16","author":"Moran","year":"2010","journal-title":"Hum. Reprod. Update"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1093\/humupd\/dmr001","article-title":"PCOS, Coronary Heart Disease, Stroke and the Influence of Obesity: A Systematic Review and Meta-Analysis","volume":"17","author":"Dekkers","year":"2011","journal-title":"Hum. Reprod. Update"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Singh, S., Pal, N., Shubham, S., Sarma, D.K., Verma, V., Marotta, F., and Kumar, M. (2023). Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics. J. Clin. Med., 12.","DOI":"10.3390\/jcm12041454"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8416763","DOI":"10.1155\/2017\/8416763","article-title":"Oxidative Stress: Harms and Benefits for Human Health","volume":"2017","author":"Pizzino","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.advms.2017.05.005","article-title":"Endogenous non-enzymatic antioxidants in the human body","volume":"63","author":"Witkowska","year":"2018","journal-title":"Adv. Med. Sci."},{"key":"ref_9","first-page":"287","article-title":"First Line Defence Antioxidants-Superoxide Dismutase (SOD), Catalase (CAT) and Glutathione Peroxidase (GPX): Their Fundamental Role in the Entire Antioxidant Defence Grid","volume":"54","author":"Ighodaro","year":"2018","journal-title":"Alex. J. Med."},{"key":"ref_10","first-page":"1225578","article-title":"ROS: Basic Concepts, Sources, Cellular Signaling, and Its Implications in Aging Pathways","volume":"2022","author":"Dantas","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zeber-Lubecka, N., Ciebiera, M., and Hennig, E.E. (2023). Polycystic Ovary Syndrome and Oxidative Stress\u2014From Bench to Bedside. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814126"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3803\/EnM.2021.958","article-title":"An Update on Contraception in Polycystic Ovary Syndrome","volume":"36","author":"Oguz","year":"2021","journal-title":"Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.beem.2012.09.004","article-title":"Characteristics and Metabolic Effects of Estrogen and Progestins Contained in Oral Contraceptive Pills","volume":"27","author":"Nath","year":"2013","journal-title":"Best. Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.contraception.2010.04.004","article-title":"The Use of Newer Progestins for Contraception","volume":"82","author":"Nath","year":"2010","journal-title":"Contraception"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.fertnstert.2018.05.004","article-title":"Recommendations from the International Evidence-Based Guideline for the Assessment and Management of Polycystic Ovary Syndrome","volume":"110","author":"Teede","year":"2018","journal-title":"Fertil. Steril."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Cauci, S., Xodo, S., Buligan, C., Colaninno, C., Barbina, M., Barbina, G., and Francescato, M.P. (2021). Oxidative Stress Is Increased in Combined Oral Contraceptives Users and Is Positively Associated with High-Sensitivity C-Reactive Protein. Molecules, 26.","DOI":"10.3390\/molecules26041070"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1007\/s00421-021-04734-0","article-title":"Temporal Changes in Blood Oxidative Stress Biomarkers across the Menstrual Cycle and with Oral Contraceptive Use in Active Women","volume":"121","author":"Quinn","year":"2021","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1089\/omi.2020.0009","article-title":"Serum Metabolome Changes in Relation to Prothrombotic State Induced by Combined Oral Contraceptives with Drospirenone and Ethinylestradiol","volume":"24","author":"Swanepoel","year":"2020","journal-title":"OMICS"},{"key":"ref_19","first-page":"4579831","article-title":"Role of Oxidative Stress in Obese and Nonobese PCOS Patients","volume":"2022","author":"Demir","year":"2022","journal-title":"Int. J. Clin. Pract."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1093\/humupd\/dmp024","article-title":"Visually Scoring Hirsutism","volume":"16","author":"Yildiz","year":"2010","journal-title":"Hum. Reprod. Update"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.clinbiochem.2004.03.008","article-title":"Validation of the Friedewald Formula for the Determination of Low-Density Lipoprotein Cholesterol Compared with \u03b2-Quantification in a Large Population","volume":"37","author":"Tremblay","year":"2004","journal-title":"Clin. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"471","DOI":"10.5001\/omj.2012.112","article-title":"Validity of Serum Testosterone, Free Androgen Index, and Calculated Free Testosterone in Women with Suspected Hyperandrogenism","volume":"27","year":"2012","journal-title":"Oman Med. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1093\/humrep\/dem146","article-title":"Effect of Different Contraceptive Methods on the Oxidative Stress Status in Women Aged 40 48 Years from the ELAN Study in the Province of Liege, Belgium","volume":"22","author":"Pincemail","year":"2007","journal-title":"Hum. Reprod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"893","DOI":"10.4103\/2008-7802.104862","article-title":"Oral Contraceptive Therapy Increases Oxidative Stress in Pre-Menopausal Women","volume":"3","author":"Chen","year":"2012","journal-title":"Int. J. Prev. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41572-024-00511-3","article-title":"Polycystic ovary syndrome","volume":"10","author":"Teede","year":"2024","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1210\/en.2005-0902","article-title":"Regulation of Hepatic Insulin-like Growth Factor-Binding Protein-1 Gene Expression by Insulin: Central Role for Mammalian Target of Rapamycin Independent of Forkhead Box O Proteins","volume":"147","author":"Mounier","year":"2006","journal-title":"Endocrinology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"91","DOI":"10.2147\/IJWH.S344542","article-title":"Effect of Sex Hormone-Binding Globulin on Polycystic Ovary Syndrome: Mechanisms, Manifestations, Genetics, and Treatment","volume":"14","author":"Xing","year":"2022","journal-title":"Int. J. Womens Health"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s00404-020-05951-2","article-title":"Association of Metabolic and Inflammatory Markers with Polycystic Ovarian Syndrome (PCOS): An Update","volume":"303","year":"2021","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1093\/humupd\/dmi005","article-title":"Combined Oral Contraceptives in the Treatment of Polycystic Ovary Syndrome","volume":"11","author":"Cibula","year":"2005","journal-title":"Hum. Reprod. Update"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"463","DOI":"10.2165\/00003495-200363050-00003","article-title":"Progestogens with Antiandrogenic Properties","volume":"63","author":"Raudrant","year":"2003","journal-title":"Drugs"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1093\/humupd\/dmw016","article-title":"Hormonal Contraceptives: Pharmacology Tailored to Women\u2019s Health","volume":"22","author":"Musacchio","year":"2016","journal-title":"Hum. Reprod. Update"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.fertnstert.2006.11.137","article-title":"Evaluation of Effects of an Oral Contraceptive Containing Ethinylestradiol Combined with Drospirenone on Adrenal Steroidogenesis in Hyperandrogenic Women with Polycystic Ovary Syndrome","volume":"88","author":"Morgante","year":"2007","journal-title":"Fertil. Steril."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.contraception.2010.04.002","article-title":"Effect of Oral Contraceptives on Markers of Hyperandrogenism and SHBG in Women with Polycystic Ovary Syndrome","volume":"82","author":"Musacchio","year":"2010","journal-title":"Contraception"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1007\/s10815-022-02625-7","article-title":"A Brief Insight into the Etiology, Genetics, and Immunology of Polycystic Ovarian Syndrome (PCOS)","volume":"39","author":"Siddiqui","year":"2022","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.mam.2011.10.006","article-title":"Oxidative Stress in Health and Disease: The Therapeutic Potential of Nrf2 Activation","volume":"32","author":"Hybertson","year":"2011","journal-title":"Mol. Aspects Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.bbamcr.2018.02.010","article-title":"Nrf2-Keap1 Signaling in Oxidative and Reductive Stress","volume":"1865","author":"Bellezza","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ngo, V., and Duennwald, M.L. (2022). Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease. Antioxidants, 11.","DOI":"10.3390\/antiox11122345"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kokosar, M., Benrick, A., Perfilyev, A., Fornes, R., Nilsson, E., Maliqueo, M., Behre, C.J., Sazonova, A., Ohlsson, C., and Ling, C. (2016). Epigenetic and Transcriptional Alterations in Human Adipose Tissue of Polycystic Ovary Syndrome. Sci. Rep., 6.","DOI":"10.1038\/srep22883"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.cbi.2017.06.009","article-title":"The Promising Effect of Linagliptin and\/or Indole-3-Carbinol on Experimentally-Induced Polycystic Ovarian Syndrome","volume":"273","author":"Kabel","year":"2017","journal-title":"Chem. Biol. Interact."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1002\/jcb.20541","article-title":"Differential Expression of Antioxidant Enzymes in Various Hepatocellular Carcinoma Cell Lines","volume":"96","author":"Yang","year":"2005","journal-title":"J. Cell. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Gonzalez-Candia, A., Veliz, M., Carrasco-Pozo, C., Castillo, R.L., C\u00e1rdenas, J.C., Ebensperger, G., Reyes, R.V., Llanos, A.J., and Herrera, E.A. (2019). Antenatal Melatonin Modulates an Enhanced Antioxidant\/pro-Oxidant Ratio in Pulmonary Hypertensive Newborn Sheep. Redox Biol., 22.","DOI":"10.1016\/j.redox.2019.101128"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/nrm2256","article-title":"ROS as Signalling Molecules: Mechanisms That Generate Specificity in ROS Homeostasis","volume":"8","author":"Toledano","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.contraception.2009.02.015","article-title":"Effects of Oral Contraception with Ethinylestradiol and Drospirenone on Oxidative Stress in Women 18\u201335 Years Old","volume":"80","author":"Pintiaux","year":"2009","journal-title":"Contraception"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1096\/fj.01-0123com","article-title":"17beta-Estradiol Inhibition of NADPH Oxidase Expression in Human Endothelial Cells","volume":"15","author":"Wagner","year":"2001","journal-title":"FASEB J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1161\/01.RES.0000188212.57180.55","article-title":"Progesterone Antagonizes the Vasoprotective Effect of Estrogen on Antioxidant Enzyme Expression and Function","volume":"97","author":"Wassmann","year":"2005","journal-title":"Circ. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1196\/annals.1347.018","article-title":"Impact of Metabolism on the Safety of Estrogen Therapy","volume":"1052","author":"Prokai","year":"2005","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.contraception.2016.07.019","article-title":"Perspectives on Variability in Pharmacokinetics of an Oral Contraceptive Product","volume":"95","author":"Jusko","year":"2017","journal-title":"Contraception"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Chai, Y.C., and Mieyal, J.J. (2023). Glutathione and Glutaredoxin-Key Players in Cellular Redox Homeostasis and Signaling. Antioxidants, 12.","DOI":"10.3390\/antiox12081553"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/bs.vh.2022.09.002","article-title":"The Antioxidant Glutathione","volume":"121","year":"2023","journal-title":"Vitam. Horm."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Liu, T., Sun, L., Zhang, Y., Wang, Y., and Zheng, J. (2022). Imbalanced GSH\/ROS and Sequential Cell Death. J. Biochem. Mol. Toxicol., 36.","DOI":"10.1002\/jbt.22942"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/10\/1168\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:03:21Z","timestamp":1760112201000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/10\/1168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,26]]},"references-count":50,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["antiox13101168"],"URL":"https:\/\/doi.org\/10.3390\/antiox13101168","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,26]]}}}