{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T08:29:37Z","timestamp":1786350577725,"version":"build-2736575974"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002794","name":"Swedish Cancer Society","doi-asserted-by":"publisher","award":["222038"],"award-info":[{"award-number":["222038"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002794","name":"Swedish Cancer Society","doi-asserted-by":"publisher","award":["254478"],"award-info":[{"award-number":["254478"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Previous studies have suggested a potential role of sex hormones in the development of liver cancer. This study aimed to examine whether menopausal hormone therapy (MHT) is associated with a decreased risk of liver cancer by histological type.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This Swedish population-based cohort study included 217\u00a0878 women who received MHT in 2006 to 2023 and an age-matched comparison group of 1\u00a0089\u00a0390 women who did not receive MHT. Cox regression assessed the associations between use of MHT and the risk of 2 main subtypes of liver cancer, that is, hepatocellular carcinoma and intrahepatic cholangiocarcinoma, with adjustment for smoking- and alcohol-related diagnoses, non-alcoholic fatty liver disease, diabetes or obesity, hysterectomy, use of non-steroidal anti-inflammatory drugs or aspirin, and use of statins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MHT users had a decreased risk of hepatocellular carcinoma (hazard ratio [HR] = 0.46, 95% confidence interval [CI] = 0.30 to 0.72). Decreased HRs of hepatocellular carcinoma were indicated both in users of estrogen only (HR = 0.42, 95% CI = 0.21 to 0.86) and estrogen combined with progestogen (HR = 0.49, 95% CI = 0.28 to 0.85). The risk reduction in hepatocellular carcinoma was apparently more pronounced in users aged 60\u2009years or older (HR = 0.37, 95% CI = 0.19 to 0.75). The use of MHT was not associated with the risk of intrahepatic cholangiocarcinoma (HR = 0.99, 95% CI = 0.72 to 1.36).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MHT in women may decrease the risk of hepatocellular carcinoma, but not intrahepatic cholangiocarcinoma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djag084","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T12:52:46Z","timestamp":1773838366000},"page":"1478-1484","source":"Crossref","is-referenced-by-count":0,"title":["Menopausal hormone therapy and risk of liver cancer in a Swedish population-based cohort study"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5705-9413","authenticated-orcid":false,"given":"Yongying","family":"Huang","sequence":"first","affiliation":[{"name":"Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital , Fuzhou,","place":["China"]},{"name":"Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet , Stockholm,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giola","family":"Santoni","sequence":"additional","affiliation":[{"name":"Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet , Stockholm,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6580-450X","authenticated-orcid":false,"given":"Jessica L","family":"Petrick","sequence":"additional","affiliation":[{"name":"Slone Epidemiology Center at Boston University , Boston, MA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5276-1314","authenticated-orcid":false,"given":"Victoria","family":"Wocalewski","sequence":"additional","affiliation":[{"name":"Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet , Stockholm,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Sparrelid","sequence":"additional","affiliation":[{"name":"Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital , Stockholm,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4270-1281","authenticated-orcid":false,"given":"Shao-Hua","family":"Xie","sequence":"additional","affiliation":[{"name":"Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet , Stockholm,","place":["Sweden"]},{"name":"School of Public Health, Fujian Medical University , Fuzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,22]]},"reference":[{"key":"2026081003523747300_djag084-B1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"2026081003523747300_djag084-B2","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1053\/j.gastro.2007.04.061","article-title":"Hepatocellular carcinoma: epidemiology and molecular carcinogenesis","volume":"132","author":"El-Serag","year":"2007","journal-title":"Gastroenterology"},{"key":"2026081003523747300_djag084-B3","doi-asserted-by":"crossref","first-page":"1073274817729245","DOI":"10.1177\/1073274817729245","article-title":"Epidemiology of hepatocellular carcinoma and intrahepatic cholangiocarcinoma","volume":"24","author":"Massarweh","year":"2017","journal-title":"Cancer Control"},{"key":"2026081003523747300_djag084-B4","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/hep.31288","article-title":"Epidemiology of hepatocellular carcinoma","volume":"73 Suppl 1","author":"McGlynn","year":"2021","journal-title":"Hepatology"},{"key":"2026081003523747300_djag084-B5","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1186\/s12889-022-12867-w","article-title":"Global pattern of trends in incidence, mortality, and mortality-to-incidence ratio rates related to liver cancer, 1990-2019: a longitudinal analysis based on the Global Burden of Disease Study","volume":"22","author":"Amini","year":"2022","journal-title":"BMC Public Health"},{"key":"2026081003523747300_djag084-B6","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/ijc.32723","article-title":"International trends in hepatocellular carcinoma incidence, 1978-2012","volume":"147","author":"Petrick","year":"2020","journal-title":"Int J Cancer"},{"key":"2026081003523747300_djag084-B7","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1002\/cncr.32803","article-title":"Global trends in intrahepatic and extrahepatic cholangiocarcinoma incidence from 1993 to 2012","volume":"126","author":"Florio","year":"2020","journal-title":"Cancer"},{"key":"2026081003523747300_djag084-B8","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1056\/NEJMcibr075652","article-title":"Hepatocellular carcinoma and sex","volume":"357","author":"Wands","year":"2007","journal-title":"N Engl J Med"},{"key":"2026081003523747300_djag084-B9","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/1479-5876-12-93","article-title":"Role of estrogen in hepatocellular carcinoma: is inflammation the key?","volume":"12","author":"Shi","year":"2014","journal-title":"J Transl Med"},{"key":"2026081003523747300_djag084-B10","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1158\/1055-9965.EPI-23-0039","article-title":"Circulating sex hormone levels and risk of gastrointestinal cancer: systematic review and meta-analysis of prospective studies","volume":"32","author":"Liu","year":"2023","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2026081003523747300_djag084-B11","doi-asserted-by":"crossref","first-page":"100742","DOI":"10.1016\/j.jhepr.2023.100742","article-title":"Endogenous sex steroid hormones and risk of liver cancer among US men: results from the Liver Cancer Pooling Project","volume":"5","author":"Wu","year":"2023","journal-title":"JHEP Rep"},{"key":"2026081003523747300_djag084-B12","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1093\/humupd\/dmw037","article-title":"Reproductive factors, menopausal hormone therapies and primary liver cancer risk: a systematic review and dose-response meta-analysis of observational studies","volume":"23","author":"Zhong","year":"2016","journal-title":"Hum Reprod Update"},{"key":"2026081003523747300_djag084-B13","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/s41416-020-0835-5","article-title":"Exogenous hormone use, reproductive factors and risk of intrahepatic cholangiocarcinoma among women: results from cohort studies in the Liver Cancer Pooling Project and the UK Biobank","volume":"123","author":"Petrick","year":"2020","journal-title":"Br J Cancer"},{"key":"2026081003523747300_djag084-B14","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1002\/ijc.35244","article-title":"Total testosterone, sex hormone-binding globulin, and free testosterone concentrations and risk of primary liver cancer: a prospective analysis of 200,000 men and 180,000 postmenopausal women","volume":"156","author":"Watling","year":"2025","journal-title":"Int J Cancer"},{"key":"2026081003523747300_djag084-B15","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/(SICI)1097-0215(19960729)67:3<327::AID-IJC4>3.0.CO;2-T","article-title":"Cancer incidence and mortality in women receiving estrogen and estrogen-progestin replacement therapy\u2014long-term follow-up of a Swedish cohort","volume":"67","author":"Persson","year":"1996","journal-title":"Int J Cancer"},{"key":"2026081003523747300_djag084-B16","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1002\/ijc.11083","article-title":"Hormone replacement therapy and cancer risk: a systematic analysis from a network of case-control studies","volume":"105","author":"Fernandez","year":"2003","journal-title":"Int J Cancer"},{"key":"2026081003523747300_djag084-B17","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1002\/ijc.29960","article-title":"Menopausal hormone therapy use and risk of primary liver cancer in the Clinical Practice Research Datalink","volume":"138","author":"McGlynn","year":"2016","journal-title":"Int J Cancer"},{"key":"2026081003523747300_djag084-B18","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1038\/bjc.2015.58","article-title":"Reproductive factors, exogenous hormone use and risk of hepatocellular carcinoma among US women: results from the Liver Cancer Pooling Project","volume":"112","author":"McGlynn","year":"2015","journal-title":"Br J Cancer"},{"key":"2026081003523747300_djag084-B19","first-page":"1393","article-title":"Role of reproductive factors in hepatocellular carcinoma: impact on hepatitis B- and C-related risk","volume":"38","author":"Yu","year":"2003","journal-title":"Hepatology"},{"key":"2026081003523747300_djag084-B20","doi-asserted-by":"crossref","first-page":"e023155","DOI":"10.1136\/bmjopen-2018-023155","article-title":"Cohort profile: the Swedish Prescribed Drugs and Health Cohort (SPREDH)","volume":"9","author":"Xie","year":"2019","journal-title":"BMJ Open"},{"key":"2026081003523747300_djag084-B21","doi-asserted-by":"crossref","first-page":"e104455","DOI":"10.1136\/bmjopen-2025-104455","article-title":"Swedish Prescribed Drugs and Health Cohort (SPREDH): cohort profile update","volume":"15","author":"Xie","year":"2025","journal-title":"BMJ Open"},{"key":"2026081003523747300_djag084-B22","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1093\/jnci\/91.9.786","article-title":"Evaluating gastric cancer misclassification: a potential explanation for the rise in cardia cancer incidence","volume":"91","author":"Ekstrom","year":"1999","journal-title":"J Natl Cancer Inst"},{"key":"2026081003523747300_djag084-B23","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1186\/1471-2458-11-450","article-title":"External review and validation of the Swedish National Inpatient Register","volume":"11","author":"Ludvigsson","year":"2011","journal-title":"BMC Public Health"},{"key":"2026081003523747300_djag084-B24","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/pds.1294","article-title":"The new Swedish Prescribed Drug Register\u2014opportunities for pharmacoepidemiological research and experience from the first six months","volume":"16","author":"Wettermark","year":"2007","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"2026081003523747300_djag084-B25","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s10654-017-0316-1","article-title":"The Swedish cause of death register","volume":"32","author":"Brooke","year":"2017","journal-title":"Eur J Epidemiol"},{"key":"2026081003523747300_djag084-B26","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1002\/sim.5879","article-title":"Ignoring the matching variables in cohort studies\u2014when is it valid and why?","volume":"32","author":"Sjolander","year":"2013","journal-title":"Stat Med"},{"key":"2026081003523747300_djag084-B27","doi-asserted-by":"crossref","first-page":"e70048","DOI":"10.1002\/pds.70048","article-title":"Core concepts in pharmacoepidemiology: new-user designs","volume":"33","author":"Her","year":"2024","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"2026081003523747300_djag084-B28","doi-asserted-by":"crossref","first-page":"e0271790","DOI":"10.1371\/journal.pone.0271790","article-title":"Hormone replacement therapy is associated with reduced hepatocellular carcinoma risk and improved survival in postmenopausal women with hepatitis B: a nationwide long-term population-based cohort study","volume":"17","author":"Wang","year":"2022","journal-title":"PLoS One"},{"key":"2026081003523747300_djag084-B29","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/aid2.13250","article-title":"Long-term effects of hormone replacement therapy on hepatocellular carcinoma risk and overall survival rate in women with chronic hepatitis C: a population-based cohort study in Taiwan","volume":"9","author":"Chang","year":"2022","journal-title":"Adv Dig Med"},{"key":"2026081003523747300_djag084-B30","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1016\/j.cgh.2017.05.036","article-title":"Estrogen replacement reduces risk and increases survival times of women with hepatocellular carcinoma","volume":"15","author":"Hassan","year":"2017","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2026081003523747300_djag084-B31","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1126\/science.1140485","article-title":"Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production","volume":"317","author":"Naugler","year":"2007","journal-title":"Science"},{"key":"2026081003523747300_djag084-B32","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1002\/cncr.11528","article-title":"The clinical and pathogenetic significance of estrogen receptor-beta expression in chronic liver diseases and liver carcinoma","volume":"98","author":"Iavarone","year":"2003","journal-title":"Cancer"},{"key":"2026081003523747300_djag084-B33","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.3390\/cancers13092085","article-title":"Estrogens in hepatocellular carcinoma: friends or foes?","volume":"13","author":"Carruba","year":"2021","journal-title":"Cancers (Basel)"},{"key":"2026081003523747300_djag084-B34","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ejca.2017.07.012","article-title":"Menopausal hormone therapy and cancer risk: an overestimated risk?","volume":"84","author":"Simin","year":"2017","journal-title":"Eur J Cancer"},{"key":"2026081003523747300_djag084-B35","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s41416-021-01575-8","article-title":"Menopausal hormone therapy and risk of oesophageal adenocarcinoma in a population-based cohort study","volume":"126","author":"Xie","year":"2022","journal-title":"Br J Cancer"}],"container-title":["JNCI: Journal of the National Cancer Institute"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jnci\/advance-article-pdf\/doi\/10.1093\/jnci\/djag084\/67472988\/djag084.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jnci\/article-pdf\/118\/8\/1478\/67472988\/djag084.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jnci\/article-pdf\/118\/8\/1478\/67472988\/djag084.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T07:52:48Z","timestamp":1786348368000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jnci\/article\/118\/8\/1478\/8537196"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,22]]},"references-count":35,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,3,22]]},"published-print":{"date-parts":[[2026,8,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jnci\/djag084","relation":{},"ISSN":["0027-8874","1460-2105"],"issn-type":[{"value":"0027-8874","type":"print"},{"value":"1460-2105","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8]]},"published":{"date-parts":[[2026,3,22]]}}}