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Survival outcomes were estimated via Kaplan\u2013Meier curves, and SMRs were calculated. Independent risk factors were identified via multivariate Cox regression, followed by stepwise Cox, sex-stratified and interaction analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During follow-up, 125 deaths (10.6%) and 33 malignancies (2.8%) occurred, both of which were more common in men (log\u2013rank tests,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). Overall mortality was markedly higher in men (25.5%, SMR\u2009=\u20094.79) than in women (8.3%, SMR\u2009=\u20092.42). Male sex was independently associated with higher risk of mortality (HR\u2009=\u20091.998,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.004) and cancer incidence (HR\u2009=\u20093.799,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.001). Sex-stratified analyses revealed distinct death\u2013associated factors: interstitial lung disease (ILD), pulmonary infection and ischemic stroke were independently associated with mortality in men, whereas older age, low C3, elevated C-reactive protein and total bilirubin (TBIL) levels were associated with mortality in women. With respect to cancer, longer disease duration, lymphadenopathy, lymphocytopenia, elevated TBIL and hypochloremia were independently associated with cancer risk in women, whereas no variables showed an independent association with cancer risk among men. Interaction analyses demonstrated additive interactions between male sex and elevated ESSDAI scores, as well as male sex and concomitant ILD, in relation to mortality.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Compared with women, men with pSD presented greater risks and distinct risk profiles of death and malignancy. Moreover, male sex was independently associated with adverse outcomes and acted as an important effect modifier, highlighting the need for sex-specific risk stratification and clinical management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>This ambispective cohort study was registered in the Clinical Trial Registry (ID: NCT06528197) on June 27, 2024 and conducted in accordance with the Declaration of Helsinki.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13293-026-00827-7","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T02:25:24Z","timestamp":1768357524000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sex differences in primary Sj\u00f6gren\u2019s disease: prognostic impact on mortality and cancer"],"prefix":"10.1186","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8935-7453","authenticated-orcid":false,"given":"Chunxin","family":"Lei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3343-1859","authenticated-orcid":false,"given":"Xiya","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanyi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bojie","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahe","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianying","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9163-8426","authenticated-orcid":false,"given":"Qingwen","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2454-2168","authenticated-orcid":false,"given":"Jing","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"827_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.47","volume":"2","author":"P Brito-Zer\u00f3n","year":"2016","unstructured":"Brito-Zer\u00f3n P, Baldini C, Bootsma H, et al. 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