{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T16:18:02Z","timestamp":1793031482342,"version":"4.5.0"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Menstruation is a daily opportunity for iron loss in women. Hepcidin (Hepc), a key regulator of iron metabolism, is known to respond to both iron status and inflammation. Menstruation is also accompanied by local and systemic production of reactive oxygen species and inflammatory responses. However, fluctuations in Hepc and oxidative stress during the menstrual cycle and their relationship are unclear. The purpose of this study was to clarify of the fluctuations Hepc and oxidative stress and relationships.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sixteen women were recruited, of whom twelve with normal menstrual cycles were included in the final analysis. Blood samples were collected at four time points \u2014 The menstrual phase (MP), follicular phase (FP), early luteal phase (ELP), and late luteal phase (LLP) \u2014 while the participants were at rest. Serum Hepc, serum ferritin (FER), and oxidative stress levels were evaluated. In addition, differences between the iron-deficient (ID, &amp;lt;12 ng\/ml) and non\u2013iron-deficient (NID, \u226512 ng\/ml) groups, classified according to FER levels during the ELP, were examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Oxidative stress showed significant fluctuations across the menstrual cycle (p &amp;lt; 0.01), with higher values during the MP and FP compared with the LLP. This trend was particularly pronounced in the ID group. Hepc did not exhibit significant cyclical fluctuations. Nevertheless, its mean level was highest in the MP and lowest in the FP. No significant correlation was observed between oxidative stress and Hepc. FER was positively correlated with Hepc only in the LP (r = 0.769, p = 0.043), and significant differences in Hepc levels between the ID and NID groups were observed exclusively in the ELP (p = 0.003) and LLP (p = 0.010).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Oxidative stress fluctuated across the menstrual cycle, with increases observed during the MP and FP. These fluctuations appeared to be more pronounced in the presence of ID. In contrast, Hepc did not exhibit consistent cyclical changes. Although oxidative stress was considered to influence Hepc elevation through inflammatory responses, no direct relationship was detected at the blood marker level.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1689305","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T04:18:12Z","timestamp":1761106692000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Fluctuations and interrelationship of oxidative stress and hepcidin during the menstrual cycle"],"prefix":"10.3389","volume":"16","author":[{"given":"Ena","family":"Yoshida","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harumi","family":"Hayashida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda J.","family":"Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiko","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"B1","article-title":"The normal menstrual cycle and the control of ovulation","volume-title":"Endotext","author":"Reed","year":"2000"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1017\/S1368980008004072","article-title":"Iron intake does not significantly correlate with iron deficiency among young Japanese women: a cross-sectional study","volume":"12","author":"Asakura","year":"2009","journal-title":"Public Health Nutr"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2009.27439","article-title":"Body iron excretion by healthy men and women","volume":"89","author":"Hunt","year":"2009","journal-title":"Am J Clin Nutr"},{"key":"B4","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.trsl.2016.08.003","article-title":"Optimizing hemoglobin thresholds for detection of iron deficiency among reproductive-age women in the United States","volume":"180","author":"Sekhar","year":"2017","journal-title":"Transl Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2007.04.016","article-title":"Evaluation of iron deficiency in young women in relation to oral contraceptive use","volume":"76","author":"Casabellata","year":"2007","journal-title":"Contraception"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0000000000000733","article-title":"Iron status of blood donors","volume":"29","author":"Spencer","year":"2022","journal-title":"Curr Opin Hematol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.11406\/rinketsu.33.1661","article-title":"Prevalence and pathogenesis of iron deficiency in Japanese women (1981-1991)","volume":"33","author":"Uchida","year":"1992","journal-title":"Rinsho Ketsueki"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-071812-161205","article-title":"Iron nutrition and premenopausal women: effects of poor iron status on physical and neuropsychological performance","volume":"33","author":"McClung","year":"2013","journal-title":"Annu Rev Nutr"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.26.061505.111303","article-title":"Regulation of iron metabolism by hepcidin","volume":"26","author":"Nemeth","year":"2006","journal-title":"Annu Rev Nutr"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2012.01.014","article-title":"Hepcidin and iron homeostasis","volume":"1823","author":"Ganz","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"B11","doi-asserted-by":"publisher","first-page":"101052","DOI":"10.1016\/j.eclinm.2021.101052","article-title":"Threshold ferritin and hepcidin concentrations indicating early iron deficiency in young women based on upregulation of iron absorption","volume":"39","author":"Galetti","year":"2021","journal-title":"EClinicalMedicine"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200420945","article-title":"IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin","volume":"113","author":"Nemeth","year":"2004","journal-title":"J Clin Invest"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-03-0672","article-title":"Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation","volume":"102","author":"Ganz","year":"2003","journal-title":"Blood"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-012-9223-7","article-title":"Inflammation, leukocytes and menstruation","volume":"13","author":"Evans","year":"2012","journal-title":"Rev Endocr Metab Disord"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1029","article-title":"ROS are critical for endometrial breakdown via NF-\u03baB-COX-2 signaling in a female mouse menstrual-like model","volume":"155","author":"Wu","year":"2014","journal-title":"Endocrinology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"17416","DOI":"10.1038\/s41598-017-17565-x","article-title":"Endometrial apoptosis and neutrophil infiltration during menstruation exhibits spatial and temporal dynamics that are recapitulated in a mouse model","volume":"7","author":"Armstrong","year":"2017","journal-title":"Sci Rep"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.5149","article-title":"Reactive oxygen species in inflammation and tissue injury","volume":"20","author":"Mittal","year":"2014","journal-title":"Antioxid Redox Signal"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e93837","DOI":"10.1371\/journal.pone.0093837","article-title":"Paraquat-induced reactive oxygen species inhibit neutrophil apoptosis via a p38 MAPK\/NF-\u03baB-IL-6\/TNF-\u03b1 positive-feedback circuit","volume":"9","author":"Wang","year":"2014","journal-title":"PloS One"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2010.178","article-title":"Crosstalk of reactive oxygen species and NF-\u03baB signaling","volume":"21","author":"Morgan","year":"2011","journal-title":"Cell Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-012-9226-4","article-title":"Endometrial haemostasis and menstruation","volume":"13","author":"Davies","year":"2012","journal-title":"Rev Endocr Metab Disord"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00031.2019","article-title":"Physiology of the endometrium and regulation of menstruation","volume":"100","author":"Critchley","year":"2020","journal-title":"Physiol Rev"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00921.2020","article-title":"Interleukin-6 is higher in naturally menstruating women compared with oral contraceptive pill users during the low-hormone phase","volume":"131","author":"Eagan","year":"2021","journal-title":"J Appl Physiol (1985)"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2015.07.008","article-title":"Effect of excess iron on oxidative stress and gluconeogenesis through hepcidin during mitochondrial dysfunction","volume":"26","author":"Lee","year":"2015","journal-title":"J Nutr Biochem"},{"key":"B24","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.freeradbiomed.2023.10.402","article-title":"Hepcidin as a key regulator of iron homeostasis triggers inflammatory features in the normal endometrium","volume":"209","author":"Izumi","year":"2023","journal-title":"Free Radic Biol Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2016.12.035","article-title":"Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress","volume":"11","author":"Sies","year":"2017","journal-title":"Redox Biol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.519","article-title":"Roles of reactive oxygen species in inflammation and cancer","volume":"5","author":"Yu","year":"2024","journal-title":"MedComm (2020)"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1177\/1933719112466301","article-title":"Oxidative cell injury as a predictor of endometriosis progression","volume":"20","author":"Carvalho","year":"2013","journal-title":"Reprod Sci"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/81.6.1390","article-title":"Oxidative stress, diet, and the etiology of preeclampsia","volume":"81","author":"Scholl","year":"2005","journal-title":"Am J Clin Nutr"},{"key":"B29","doi-asserted-by":"publisher","first-page":"oeac001","DOI":"10.1093\/ehjopen\/oeac001","article-title":"Endometriosis and cardiovascular disease","volume":"2","author":"Marchandot","year":"2022","journal-title":"Eur Heart J Open"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s00265-016-2091-5","article-title":"Oxidative stress ecology and the d-ROMs test: facts, misfacts and an appraisal of a decade\u2019s work","volume":"70","author":"Costantini","year":"2016","journal-title":"Behav Ecol Sociobiol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1097\/00006842-196811000-00006","article-title":"The development of a menstrual distress questionnaire","volume":"30","author":"Moos","year":"1968","journal-title":"Psychosom Med"},{"key":"B32","article-title":"Japanese version of the menstrual distress questionnaire (MDQ: menstrual distress questionnaire) by akiyama and kayashima (1979)","volume-title":"Psychometric Scales III: Measuring Mental Health \u2013 Adaptation and Clinical Aspects","author":"Akiyama","year":"2001"},{"key":"B33","volume-title":"Ferritin Laboratory Procedure Manual (NHANES 2015\u20132016)","year":"2016"},{"key":"B34","doi-asserted-by":"publisher","first-page":"418","DOI":"10.3390\/nu16030418","article-title":"Factors associated with anemia and iron deficiency during pregnancy: A prospective observational study in Japan","volume":"16","author":"Habe","year":"2024","journal-title":"Nutrients"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1089\/whr.2021.0067","article-title":"The concentration of 8-hydroxy-2\u2019-deoxyguanosine in plasma during the menstrual cycle in young Japanese women","volume":"3","author":"Yama","year":"2022","journal-title":"Womens Health Rep (New Rochelle)"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1179\/135100008X308993","article-title":"Changes of markers of oxidative stress during menstrual cycle","volume":"13","author":"Karowicz-Bilinska","year":"2008","journal-title":"Redox Rep"},{"key":"B37","doi-asserted-by":"publisher","first-page":"829","DOI":"10.3390\/jcm12030829","article-title":"Impact of menopause and the menstrual cycle on oxidative stress in Japanese women","volume":"12","author":"Ishikawa","year":"2023","journal-title":"J Clin Med"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/10715762.2019.1702656","article-title":"Hormones and oxidative stress: an overview","volume":"54","author":"Chainy","year":"2020","journal-title":"Free Radic Res"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1080\/14017430510035862","article-title":"The association of total antioxidant capacity with sex hormones","volume":"39","author":"Demirbag","year":"2005","journal-title":"Scand Cardiovasc J"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1080\/00016340500453685","article-title":"Estrogens are potentially the only steroids with an antioxidant role in pregnancy: in vitro evidence","volume":"85","author":"Reyes","year":"2006","journal-title":"Acta Obstet Gynecol Scand"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.20335","article-title":"Oxidative status in iron-deficiency anemia","volume":"23","author":"Yoo","year":"2009","journal-title":"J Clin Lab Anal"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.2220\/biomedres.38.343","article-title":"Iron deficiency induces autophagy and activates Nrf2 signal through modulating p62\/SQSTM","volume":"38","author":"Inoue","year":"2017","journal-title":"BioMed Res"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1080\/09168451.2015.1018125","article-title":"Activation of Nrf2\/Keap1 signaling and autophagy induction against oxidative stress in heart in iron deficiency","volume":"79","author":"Inoue","year":"2015","journal-title":"Biosci Biotechnol Biochem"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13906","article-title":"Variations of hepcidin and iron-status parameters during the menstrual cycle in healthy women","volume":"175","author":"Lain\u00e9","year":"2016","journal-title":"Br J Haematol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fspor.2022.903937","article-title":"A contemporary understanding of iron metabolism in active premenopausal females","volume":"4","author":"Badenhorst","year":"2022","journal-title":"Front Sports Act Living"},{"key":"B46","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1208\/s12248-016-9875-4","article-title":"Joint model of iron and hepcidin during the menstrual cycle in healthy women","volume":"18","author":"Angeli","year":"2016","journal-title":"AAPS J"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/s00421-022-05048-5","article-title":"Menstrual cycle affects iron homeostasis and hepcidin following interval running exercise in endurance-trained women","volume":"122","author":"Alfaro-Magallanes","year":"2022","journal-title":"Eur J Appl Physiol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s43162-022-00098-9","article-title":"Interplay of serum hepcidin with female sex hormones, metabolic syndrome, and abdominal fat distribution among premenopausal and postmenopausal women","volume":"34","author":"Matta","year":"2022","journal-title":"Egyptian J Internal Med"},{"key":"B49","doi-asserted-by":"publisher","first-page":"115495","DOI":"10.1016\/j.bone.2020.115495","article-title":"Bone morphogenic proteins in iron homeostasis","volume":"138","author":"Xiao","year":"2020","journal-title":"Bone"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-06-027631","article-title":"Interleukin-6 induces hepcidin expression through STAT3","volume":"108","author":"Wrighting","year":"2006","journal-title":"Blood"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwr356","article-title":"Menstrual bleeding patterns among regularly menstruating women","volume":"175","author":"Dasharathy","year":"2012","journal-title":"Am J Epidemiol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2014.01.027","article-title":"Urinary cytokine and chemokine profiles across the menstrual cycle in healthy reproductive-aged women","volume":"101","author":"Whitcomb","year":"2014","journal-title":"Fertil Steril"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/58.5.705","article-title":"Variations in iron-status measures during the menstrual cycle","volume":"58","author":"Kim","year":"1993","journal-title":"Am J Clin Nutr"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1079\/BJN20051461","article-title":"Day-to-day variation in iron-status measures in young iron-deplete women","volume":"94","author":"Belza","year":"2005","journal-title":"Br J Nutr"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1080\/17461391.2021.2018503","article-title":"Serum iron availability, but not iron stores, is lower in naturally menstruating than in oral contraceptive athletes","volume":"23","author":"Alfaro-Magallanes","year":"2023","journal-title":"Eur J Sport Sci"},{"key":"B56","doi-asserted-by":"publisher","first-page":"589","DOI":"10.3390\/microorganisms8040589","article-title":"Ferritin: an inflammatory player keeping iron at the core of pathogen-host interactions","volume":"8","author":"Moreira","year":"2020","journal-title":"Microorganisms"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3109\/13506129909007314","article-title":"Ferritin correlates with C-reactive protein and acute phase serum amyloid A in synovial fluid, but not in serum","volume":"6","author":"Kumon","year":"1999","journal-title":"Amyloid"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.4103\/2305-0500.346088","article-title":"Oxidative stress and female reproductive disorder: a review","volume":"11","author":"Manokaran","year":"2022","journal-title":"Asian Pacific J Reproduction"},{"key":"B59","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/1477-7827-3-28","article-title":"Role of oxidative stress in female reproduction","volume":"3","author":"Agarwal","year":"2005","journal-title":"Reprod Biol Endocrinol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1359600","article-title":"ROS signaling in innate immunity via oxidative protein modifications","volume":"15","author":"Manoharan","year":"2024","journal-title":"Front Immunol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.7600\/jpfsm.1.183","article-title":"Effects of different intensities of endurance exercise on oxidative stress and antioxidant capacity","volume":"1","author":"Takahashi","year":"2012","journal-title":"J Phys Fitness Sports Med"},{"key":"B62","first-page":"1","article-title":"Influence of menstrual cycle on oxidative stress and endurance performance in female athletes","volume":"12","author":"Ikeda","year":"2023","journal-title":"Japanese J Sports Rehabilitation"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1123\/ijsnem.19.6.583","article-title":"Effects of exercise on hepcidin response and iron metabolism during recovery","author":"Peeling","year":"2009","journal-title":"Int J Sport Nutr Exerc Metab"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11705","article-title":"Hepcidin: from discovery to differential diagnosis","volume":"93","author":"Kemna","year":"2008","journal-title":"Haematologica"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.10058","article-title":"Detection of ovulation, a review of currently available methods","volume":"2","author":"Su","year":"2017","journal-title":"Bioeng Transl Med"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsams.2016.08.013","article-title":"Three-step method for menstrual and oral contraceptive cycle verification","volume":"20","author":"Schaumberg","year":"2017","journal-title":"J Sci Med Sport"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1689305\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T04:18:17Z","timestamp":1761106697000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1689305\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,22]]},"references-count":66,"alternative-id":["10.3389\/fendo.2025.1689305"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1689305","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,22]]},"article-number":"1689305"}}