{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T11:15:37Z","timestamp":1782645337639,"version":"3.54.5"},"reference-count":39,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014653","name":"Manchester Biomedical Research Centre","doi-asserted-by":"publisher","award":["IS\u2010BRC\u20101215\u201020007"],"award-info":[{"award-number":["IS\u2010BRC\u20101215\u201020007"]}],"id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJOG"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate serum human epididymis\u20104 (HE4) as a predictive biomarker of intrauterine progestin response in endometrial cancer and atypical endometrial hyperplasia (AEH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Prospective prognostic factor study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Consecutive sample of women attending a tertiary gynaecological oncology centre in northwest England.<\/jats:p><\/jats:sec><jats:sec><jats:title>Population<\/jats:title><jats:p>Women with AEH or early\u2010stage, low\u2010grade endometrial cancer who were unfit for or declined primary surgical management.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 76 women, 32 with AEH and 44 with endometrial cancer, were treated with a levonorgestrel intrauterine system (LNG\u2010IUS) for 12\u2009months. Endometrial biopsies and imaging were performed to assess treatment response. Pretreatment serum HE4 was analysed by chemiluminescence immunoassay and diagnostic accuracy and logistic regression analyses were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcome Measures<\/jats:title><jats:p>Progestin response at 12\u2009months defined by histology and imaging.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The median age and body mass index (BMI) of the final cohort were 52\u2009years (interquartile range [IQR] 33\u201362\u2009years) and 46\u2009kg\/m<jats:sup>2<\/jats:sup> (IQR 38\u201354\u2009kg\/m<jats:sup>2<\/jats:sup>), respectively. Baseline serum HE4 was significantly higher in non\u2010responders than responders (119.2\u00a0pmol\/L, IQR 94.0\u2013208.4\u00a0pmol\/L versus 71.8\u00a0pmol\/L, IQR 56.1\u201384.2\u00a0pmol\/L, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Older age (odds ratio [OR] 0.96, 95% CI 0.93\u20130.99, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.02), baseline serum HE4 (OR 0.97, 95% CI 0.96\u20130.99, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.001) and endometrial cancer histology (OR 0.22, 95% CI 0.72\u20130.68, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.009) were associated with a lower likelihood of progestin treatment response. Serum HE4 remained independently associated with progestin treatment failure when adjusted for age and histology (adjusted hazard ratio 0.97, 95% CI 0.96\u20130.99, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.008).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Serum HE4 shows promise as a predictive biomarker of progestin treatment response in endometrial cancer and AEH.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1471-0528.17417","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T14:18:58Z","timestamp":1675088338000},"page":"941-948","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Serum HE4 predicts progestin treatment response in endometrial cancer and atypical hyperplasia: A prognostic study"],"prefix":"10.1111","volume":"130","author":[{"given":"Chloe E.","family":"Barr","sequence":"first","affiliation":[{"name":"Department of Gynaecology, St Mary's Hospital Manchester University NHS Foundation Trust  Manchester UK"},{"name":"Division of Cancer Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie C.","family":"Sergeant","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health, School of Health Sciences, Centre for Biostatistics University of Manchester  Manchester UK"},{"name":"Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research University of Manchester, Manchester Academic Health Science Centre  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather J.","family":"Agnew","sequence":"additional","affiliation":[{"name":"Department of Gynaecology, St Mary's Hospital Manchester University NHS Foundation Trust  Manchester UK"},{"name":"Division of Cancer Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Bolton","sequence":"additional","affiliation":[{"name":"Department of Histopathology, Manchester Royal Infirmary Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhona J.","family":"McVey","sequence":"additional","affiliation":[{"name":"Department of Histopathology, Manchester Royal Infirmary Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0284-8630","authenticated-orcid":false,"given":"Emma J.","family":"Crosbie","sequence":"additional","affiliation":[{"name":"Department of Gynaecology, St Mary's Hospital Manchester University NHS Foundation Trust  Manchester UK"},{"name":"Division of Cancer Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,15]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"Cancer Research UK (CRUK).Uterine cancer incidence statistics[cited 2022 June 21]. Available from:https:\/\/www.cancerresearchuk.org\/health\u2010professional\/cancer\u2010statistics\/statistics\u2010by\u2010cancer\u2010type\/uterine\u2010cancer\/incidence"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70591-6"},{"issue":"2","key":"e_1_2_12_4_1","first-page":"232","article-title":"New concepts for an old problem: the diagnosis of endometrial hyperplasia","volume":"23","author":"Sanderson PA","year":"2017","journal-title":"Hum Reprod Update"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-10-0832"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00323-3"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2021.11.423"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.16346"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2015.12.010"},{"key":"e_1_2_12_10_1","article-title":"Levonorgestrel\u2010releasing intrauterine system for endometrial hyperplasia","volume":"9","author":"Mittermeier T","year":"2020","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.14490"},{"issue":"12","key":"e_1_2_12_12_1","article-title":"The emerging epidemic of endometrial cancer: time to take action","volume":"22","author":"Crosbie E","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-21-0229"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.890908"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/aogs.12235"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-017-2115-1"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12020276"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2016.08.333"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dji237"},{"key":"e_1_2_12_20_1","volume-title":"WHO classification of tumours female genital tumours","author":"Herrington CS","year":"2020"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470770771"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2020.08.032"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/IGC.0000000000000669"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2021.01.029"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13194764"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2016.247"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001380"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001381"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/ijgc-2020-001309"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.14491"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S327381"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2011.109"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijgo.13140"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2015.11.020"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.3109\/01443615.2016.1174199"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.5306\/wjco.v11.i6.378"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2020.11.004"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gore.2021.100732"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/aogs.13587"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/tog.12601"}],"container-title":["BJOG: An International Journal of Obstetrics &amp; Gynaecology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1471-0528.17417","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1471-0528.17417","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1471-0528.17417","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T08:56:28Z","timestamp":1692435388000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1111\/1471-0528.17417"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,15]]},"references-count":39,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1111\/1471-0528.17417"],"URL":"https:\/\/doi.org\/10.1111\/1471-0528.17417","archive":["Portico"],"relation":{},"ISSN":["1470-0328","1471-0528"],"issn-type":[{"value":"1470-0328","type":"print"},{"value":"1471-0528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,15]]},"assertion":[{"value":"2022-08-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}