{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:46:16Z","timestamp":1785732376724,"version":"3.56.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001702","name":"AO Foundation","doi-asserted-by":"publisher","award":["Research Grant for Young Researchers 2022"],"award-info":[{"award-number":["Research Grant for Young Researchers 2022"]}],"id":[{"id":"10.13039\/501100001702","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["546925525"],"award-info":[{"award-number":["546925525"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Women show lower mortality and fewer complications than men after severe polytrauma, but underlying mechanisms remain unclear. In this context, reproductive hormones have gained increasing attention. In particular, oestradiol is controversially discussed: experimental studies suggest protective effects, whereas clinical studies link elevated levels to systemic inflammation and adverse outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Therefore, in this prospective cohort study, patients with polytrauma(injury severity score \u226516) were enrolled. Hormones (oestradiol, progesterone, testosterone, luteinising hormone [LH], follicle-stimulating hormone [FSH]) were measured on admission and daily on days 1\u20135. Longitudinal changes were analysed with repeated-measures models. Associations with injury severity and clinical outcomes (organ failure, length of stay, mortality) were assessed using correlation and regression analyses adjusted for relevant confounders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>128 patients, progesterone, testosterone, LH, and FSH declined significantly over time, whereas oestradiol showed an early rise with a peak around the second day followed by a decline. Sex-specific differences were observed for testosterone, LH, and FSH, but not for oestradiol. Elevated oestradiol levels and post-traumatic increases were independently associated with injury severity and adverse outcomes, including organ failure, longer stay and mortality, after adjustment for injury severity. These findings were consistent across different oestradiol metrics (peak, area under the curve, and absolute change).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>be an integral component of the early systemic response to polytrauma and are associated with injury severity and adverse outcomes. These findings challenge the concept of oestradiol as a uniformly protective factor and support its role as a marker of post-traumatic stress and systemic dysregulation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1878946","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:28:15Z","timestamp":1785731295000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Oestradiol dynamics after polytrauma are linked to injury severity and adverse outcomes"],"prefix":"10.3389","volume":"17","author":[{"given":"Gregor","family":"Bielesch","sequence":"first","affiliation":[{"name":"Department of Trauma Surgery, TUM Klinikum rechts der Isar, Technical University of Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conrad","family":"Ketzer","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery, TUM Klinikum rechts der Isar, Technical University of Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoria","family":"Hess","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery, TUM Klinikum rechts der Isar, Technical University of Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Kirstein","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery, TUM Klinikum rechts der Isar, Technical University of Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Aasen-Hartz","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery, TUM Klinikum rechts der Isar, Technical University of Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Resch","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery, TUM Klinikum rechts der Isar, Technical University of Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Biberthaler","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery, TUM Klinikum rechts der Isar, Technical University of Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Hanschen","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery, TUM Klinikum rechts der Isar, Technical University of Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Bohe","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery, TUM Klinikum rechts der Isar, Technical University of Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0000000000000199","article-title":"Epidemiology and risk factors of multiple-organ failure after multiple trauma: an analysis of 31,154 patients from the TraumaRegister DGU","volume":"76","author":"Fr\u00f6hlich","year":"2014","journal-title":"J Trauma Acute Care Surg"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12155111","article-title":"Effect of injury patterns on the development of complications and trauma-induced mortality in patients suffering multiple trauma","volume":"12","author":"Becker","year":"2023","journal-title":"J Clin Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1186\/s13054-023-04637-w","article-title":"Heterogeneity in defining multiple trauma: a systematic review of randomized controlled trials","volume":"27","author":"Jeanmougin","year":"2023","journal-title":"Crit Care"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-200211001-00012","article-title":"Multiple trauma in children: critical care overview","volume":"30","author":"Wetzel","year":"2002","journal-title":"Crit Care Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1038\/scientificamerican0883-28","article-title":"Trauma. Accidental and intentional injuries account for more years of life lost in the U.S. than cancer and heart disease. Among the prescribed remedies are improved preventive efforts, speedier surgery and further research","volume":"249","author":"Trunkey","year":"1983","journal-title":"Sci Am"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2009.05.006","article-title":"Patterns of mortality and causes of death in polytrauma patients--has anything changed","volume":"40","author":"Pfeifer","year":"2009","journal-title":"Injury"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s004230050121","article-title":"Clinical and pathophysiological significance of severe neurotrauma in polytraumatized patients","volume":"383","author":"Meixensberger","year":"1998","journal-title":"Langenbecks Arch Surg"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148844","article-title":"Mortality patterns in patients with multiple trauma: a systematic review of autopsy studies","volume":"11","author":"Pfeifer","year":"2016","journal-title":"PloS One"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.991048","article-title":"Traumatized triad of complementopathy, endotheliopathy, and coagulopathy - impact on clinical outcomes in severe polytrauma patients","volume":"13","author":"Yang","year":"2022","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.injury.2004.12.037","article-title":"Pathophysiology of polytrauma","volume":"36","author":"Keel","year":"2005","journal-title":"Injury"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2022.04.009","article-title":"Pathophysiology in patients with polytrauma","volume":"53","author":"Pape","year":"2022","journal-title":"Injury"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11185315","article-title":"Traumatic brain injury induces a differential immune response in polytrauma patients; prospective analysis of CD69 expression on T cells and platelet expansion","volume":"11","author":"Ditsch","year":"2022","journal-title":"J Clin Med"},{"key":"B13","doi-asserted-by":"crossref","DOI":"10.3390\/cimb47070510","article-title":"CD63 immunological activation versus hemostatic function: platelet alterations after polytrauma","volume-title":"Current Issues in Molecular Biology","author":"Roemmermann","year":"2025"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-021-09258-5","article-title":"Platelets differentially modulate CD4(+) Treg activation via GPIIa\/IIIb-, fibrinogen-, and PAR4-dependent pathways","volume":"70","author":"Bock","year":"2022","journal-title":"Immunol Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.974519","article-title":"The outcome of severely injured patients following traumatic brain injury is affected by gender-a retrospective, multicenter, matched-pair analysis utilizing data of the TraumaRegister DGU(\u00ae)","volume":"16","author":"Mair","year":"2022","journal-title":"Front Neurosci"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjsurg.2015.03.021","article-title":"The influence of sex on outcomes in trauma patients: a meta-analysis","volume":"210","author":"Liu","year":"2015","journal-title":"Am J Surg"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1097\/shk.0000000000002357","article-title":"Effect of gender on 28-day survival rates and transfusion volume in severe trauma patients: a multicenter observational study","volume":"62","author":"Tsuchida","year":"2024","journal-title":"Shock"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2016.03.005","article-title":"Influence of gender on systemic IL-6 levels, complication rates and outcome after major trauma","volume":"221","author":"M\u00f6rs","year":"2016","journal-title":"Immunobiology"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2014.08.013","article-title":"Female sex protects from organ failure and sepsis after major trauma haemorrhage","volume":"45","author":"Trentzsch","year":"2014","journal-title":"Injury"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1097\/sla.0000000000000789","article-title":"The role of biological sex in severely traumatized patients on outcomes: a matched-pair analysis","volume":"261","author":"Trentzsch","year":"2015","journal-title":"Ann Surg"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-34399-0","article-title":"Sex and age specific hormonal patterns in healthy Chinese individuals: a cross-sectional study of reproductive hormones","volume":"16","author":"Ahamed","year":"2026","journal-title":"Sci Rep"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/hvaf039","article-title":"A comprehensive review of estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone in the context of laboratory medicine to support women's health","volume":"71","author":"Greene","year":"2025","journal-title":"Clin Chem"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgz196","article-title":"Sex-specific estrogen levels and reference intervals from infancy to late adulthood determined by LC-MS\/MS","volume":"105","author":"Frederiksen","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-45-4-617","article-title":"Progesterone and 5alpha-pregnane-3,20-dione in peripheral blood of normal young women: daily measurements throughout the menstrual cycle","volume":"45","author":"Milewich","year":"1977","journal-title":"J Clin Endocrinol Metab"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.humrep.a136796","article-title":"The effect of age on the cyclical patterns of plasma LH, FSH, oestradiol and progesterone in women with regular menstrual cycles","volume":"3","author":"Lee","year":"1988","journal-title":"Hum Reprod"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.1976.tb00517.x","article-title":"Luteinizing hormone and follicle stimulating hormone and the response to luteinizing hormone releasing hormone in relation to sex and age","volume":"6","author":"Lindholm","year":"1976","journal-title":"Eur J Clin Invest"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(66)90142-9","article-title":"Radioimmunoassay for luteinizing hormone in human plasma or serum: physiological studies","volume":"46","author":"Odell","year":"1967","journal-title":"J Clin Invest"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adu6094","article-title":"Steroid hormone levels vary with sex, aging, lifestyle, and genetics","volume":"11","author":"Deltourbe","year":"2025","journal-title":"Sci Adv"},{"key":"B29","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/cen.13840","article-title":"Large divergence in testosterone concentrations between men and women: frame of reference for elite athletes in sex-specific competition in sports, a narrative review","volume":"90","author":"Clark","year":"2019","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1056\/nejmra052529","article-title":"The biology of human sex differences","volume":"354","author":"Federman","year":"2006","journal-title":"N Engl J Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s002689900223","article-title":"Relations among plasma prolactin, testosterone, and injury severity in war casualties","volume":"21","author":"Cernak","year":"1997","journal-title":"World J Surg"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-6576.1992.tb03436.x","article-title":"Serum steroids and prolactin during and after major surgical trauma","volume":"36","author":"Lindh","year":"1992","journal-title":"Acta Anaesthesiol Scand"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1097\/ta.0b013e318270db12","article-title":"The effects of craniocerebral and extracranial trauma on the changes in serum testosterone and estradiol in the early stage and their clinical significance","volume":"74","author":"Gang","year":"2013","journal-title":"J Trauma Acute Care Surg"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1097\/ta.0000000000000550","article-title":"The early evolving sex hormone environment is associated with significant outcome and inflammatory response differences after injury","volume":"78","author":"Zolin","year":"2015","journal-title":"J Trauma Acute Care Surg"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2010.1586","article-title":"Acute serum hormone levels: characterization and prognosis after severe traumatic brain injury","volume":"28","author":"Wagner","year":"2011","journal-title":"J Neurotrauma"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.2139\/ssrn.3369777","article-title":"Mapping the steroid response to major trauma from injury to recovery: a prospective cohort study","volume":"105","author":"Foster","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.psyneuen.2015.02.018","article-title":"Correlation of brain levels of progesterone and dehydroepiandrosterone with neurological recovery after traumatic brain injury in female mice","volume":"56","author":"Lopez-Rodriguez","year":"2015","journal-title":"Psychoneuroendocrinology"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-1678","article-title":"Steroid profiling in brain and plasma of male and pseudopregnant female rats after traumatic brain injury: analysis by gas chromatography\/mass spectrometry","volume":"148","author":"Meffre","year":"2007","journal-title":"Endocrinology"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1411090","article-title":"A clinical trial of progesterone for severe traumatic brain injury","volume":"371","author":"Skolnick","year":"2014","journal-title":"N Engl J Med"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1404304","article-title":"Very early administration of progesterone for acute traumatic brain injury","volume":"371","author":"Wright","year":"2014","journal-title":"N Engl J Med"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000044805","article-title":"Influence of traumatic brain injury on serum levels of pituitary, thyroid, adrenal and gonadal hormones","volume":"104","author":"Zhang","year":"2025","journal-title":"Med (Baltimore)"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1097\/shk.0b013e3181506ee5","article-title":"The influence of sex hormones on coagulation and inflammation in the trauma patient","volume":"29","author":"Gee","year":"2008","journal-title":"Shock"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3109\/02699052.2016.1144081","article-title":"Longitudinal sex and stress hormone profiles among reproductive age and post-menopausal women after severe TBI: a case series analysis","volume":"30","author":"Ranganathan","year":"2016","journal-title":"Brain Inj"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00029","article-title":"Luteinizing hormone and testosterone levels during acute phase of severe traumatic brain injury: prognostic implications for adult male patients","volume":"9","author":"Hohl","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B45","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1186\/s13054-021-03844-7","article-title":"17\u03b1-Ethinyl estradiol-3-sulfate increases survival and hemodynamic functioning in a large animal model of combined traumatic brain injury and hemorrhagic shock: a randomized control trial","volume":"25","author":"Mayer","year":"2021","journal-title":"Crit Care"},{"key":"B46","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1097\/shk.0000000000000670","article-title":"The role and use of estrogens following trauma","volume":"46","author":"Weniger","year":"2016","journal-title":"Shock"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2018.5677","article-title":"Estradiol to androstenedione ratios moderate the relationship between neurological injury severity and mortality risk after severe traumatic brain injury","volume":"36","author":"Ranganathan","year":"2019","journal-title":"J Neurotrauma"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2019.6577","article-title":"Temporal acute serum estradiol and tumor necrosis factor-\u03b1 associations and risk of death after severe traumatic brain injury","volume":"37","author":"Kumar","year":"2020","journal-title":"J Neurotrauma"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1097\/01.ccm.0000292015.16171.6d","article-title":"Estradiol is associated with mortality in critically ill trauma and surgical patients","volume":"36","author":"May","year":"2008","journal-title":"Crit Care Med"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-129-3-199808010-00012","article-title":"Interactions between the hypothalamic-pituitary-adrenal axis and the female reproductive system: clinical implications","volume":"129","author":"Chrousos","year":"1998","journal-title":"Ann Intern Med"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1210\/er.13.3.476","article-title":"Intracellular signaling in the gonads","volume":"13","author":"Leung","year":"1992","journal-title":"Endocr Rev"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1210\/jc.76.6.1542","article-title":"Differential changes in serum concentrations of androgens and estrogens (in relation with cortisol) in postmenopausal women with acute illness","volume":"76","author":"Spratt","year":"1993","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1878946\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:28:16Z","timestamp":1785731296000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1878946\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,3]]},"references-count":52,"alternative-id":["10.3389\/fendo.2026.1878946"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1878946","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,3]]},"article-number":"1878946"}}