{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T19:32:47Z","timestamp":1783366367172,"version":"3.54.6"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T00:00:00Z","timestamp":1589155200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Human epididymis secretory protein 4 (HE4) is a new ovarian cancer biomarker. The factors influencing HE4 levels are not clear, and the reference data in China are limited. Here, we aim to evaluate the effects of menopause and age on HE4 levels and to provide a possible reference value for HE4 in healthy Chinese people.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>A total of 2493 healthy females aged 40 years or older were recruited from March 2013 to March 2017 with the cooperation of four medical institutions across Beijing, China. The serum levels of HE4 and cancer antigen 125 (CA125) were measured by enzyme-linked immunosorbent assay. The Wilcoxon rank-sum test of variance and a stratified analysis were used to analyze the relationships among age, menopausal status, and levels of HE4 or CA125. Confidence intervals (5%\u201395%) were determined for reference ranges in different populations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>There was a statistically significant difference in median HE4 levels between the post-menopausal (<jats:italic toggle=\"yes\">n<\/jats:italic>\u200a=\u200a2168) and pre-menopausal groups (<jats:italic toggle=\"yes\">n<\/jats:italic>\u200a=\u200a325) (36.46 <jats:italic toggle=\"yes\">vs<\/jats:italic>. 24.04 pmol\/L, <jats:italic toggle=\"yes\">Z<\/jats:italic>\u200a=\u200a\u221214.41, <jats:italic toggle=\"yes\">P<\/jats:italic>\u200a&lt;\u200a0.001). HE4 increased significantly with age in the post-menopausal groups (<jats:italic toggle=\"yes\">H<\/jats:italic>\u200a=\u200a408.18, <jats:italic toggle=\"yes\">P<\/jats:italic>\u200a&lt;\u200a0.001) but not in the pre-menopausal subjects (<jats:italic toggle=\"yes\">Z<\/jats:italic>\u200a=\u200a\u22120.43, <jats:italic toggle=\"yes\">P<\/jats:italic>\u200a=\u200a0.67). The upper 95th percentile of HE4 levels were 44.63 pmol\/L for pre-menopausal women, 78.17 pmol\/L for post-menopausal women, and 73.3 pmol\/L for all women. In the post-menopausal population, the HE4 reference ranges were 13.15 to 47.31, 14.31 to 58.04, 17.06 to 73.51, 24.50 to 115.25, and 35.71 to 212.37 pmol\/L for different age groups from forty divided by decade. The CA125 level was affected mainly by menopausal status and not age.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Menopausal status and age were both important factors influencing the level of HE4, and age affected HE4 levels mainly in post-menopausal women. The HE4 level was higher in the post-menopausal population than in the pre-menopausal population and increased with age.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/cm9.0000000000000785","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T17:31:24Z","timestamp":1589304684000},"page":"1285-1291","source":"Crossref","is-referenced-by-count":19,"title":["Age and menopausal status are important factors influencing the serum human epididymis secretory protein 4 level: a prospective cross-sectional study in healthy Chinese people"],"prefix":"10.1097","volume":"133","author":[{"given":"Hong-Yan","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University Peoples Hospital, Beijing 100044, China"},{"name":"Center of Gynecologic Oncology, Peking University Peoples Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zeng","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Research Center, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University Peoples Hospital, Beijing 100044, China"},{"name":"Center of Gynecologic Oncology, Peking University Peoples Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Qiong","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University Peoples Hospital, Beijing 100044, China"},{"name":"Center of Gynecologic Oncology, Peking University Peoples Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Jian","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University Peoples Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Ling","family":"Chu","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Research Center, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Research Center, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Rong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Nong","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Beijing Cancer Hospital, Beijing 100036, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Hong","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University Peoples Hospital, Beijing 100044, China"},{"name":"Center of Gynecologic Oncology, Peking University Peoples Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Peking University Peoples Hospital, Beijing 100044, China"},{"name":"Center of Gynecologic Oncology, Peking University Peoples Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,5,11]]},"reference":[{"key":"R1-20230813","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer statistics, 2019","volume":"69","author":"Siegel","year":"2019","journal-title":"CA Cancer J Clin"},{"key":"R2-20230813","doi-asserted-by":"crossref","first-page":"29","DOI":"10.5468\/OGS.2013.56.1.29","article-title":"Prognostic value of serum CA-125 in patients with advanced epithelial ovarian cancer followed by complete remission after adjuvant chemotherapy","volume":"56","author":"Moon","year":"2013","journal-title":"Obstet Gynecol Sci"},{"key":"R3-20230813","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1373\/clinchem.2010.157073","article-title":"Comparison of serum human epididymis protein 4 with cancer antigen 125 as a tumor marker in patients with malignant and nonmalignant 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Gynecol Reprod Biol"},{"key":"R7-20230813","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-405211-6.00001-2","article-title":"Human epididymis protein 4 in cancer diagnostics: a promising and reliable tumor marker","volume":"59","author":"Speeckaert","year":"2013","journal-title":"Adv Clin Chem"},{"key":"R8-20230813","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1136\/jclinpath-2012-201031","article-title":"Serum human epididymis protein 4 vs. carbohydrate antigen 125 for ovarian cancer diagnosis: a systematic review","volume":"66","author":"Ferraro","year":"2013","journal-title":"J Clin Pathol"},{"key":"R9-20230813","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.ygyno.2012.11.026","article-title":"Comparison of HE4, CA125 and ROMA algorithm in women with a pelvic mass: correlation with pathological outcome","volume":"128","author":"Sandri","year":"2013","journal-title":"Gynecol 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Cancer"},{"key":"R13-20230813","first-page":"309","article-title":"Usefulness of human epididymis protein 4 in predicting cytoreductive surgical outcomes for advanced ovarian tubal and peritoneal carcinoma","volume":"27","author":"Tang","year":"2015","journal-title":"Chin J Cancer Res"},{"key":"R14-20230813","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1007\/s13277-012-0471-7","article-title":"Does HE4 have a role as biomarker in the recurrence of ovarian cancer?","volume":"33","author":"Plotti","year":"2012","journal-title":"Tumor Biol"},{"key":"R15-20230813","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1080\/14737140.2017.1360138","article-title":"The role of novel biomarker HE4 in the diagnosis, prognosis and follow-up of ovarian cancer: a systematic review","volume":"17","author":"Scaletta","year":"2017","journal-title":"Expert Rev Anticancer 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Prev"},{"key":"R25-20230813","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.ygyno.2016.07.100","article-title":"Diagnostic performance and establishment of reference limits of HE4 in Korean healthy women","volume":"143","author":"Yu","year":"2016","journal-title":"Gynecol Oncol"}],"container-title":["Chinese Medical 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