{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T08:26:33Z","timestamp":1787214393131,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2017YFC0907200"],"award-info":[{"award-number":["2017YFC0907200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2017YF0907201"],"award-info":[{"award-number":["2017YF0907201"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81230016"],"award-info":[{"award-number":["81230016"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82103944"],"award-info":[{"award-number":["82103944"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Obstet Gynecol Scand"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The cardiovascular effects of hormone replacement therapy (HRT) remain controversial. This study investigated HRT\u2010associated atherosclerotic cardiovascular disease (ASCVD) risk, focusing on reproductive characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods<\/jats:title>\n                    <jats:p>This prospective cohort study analyzed 170\u2009250 women aged 40\u201369\u2009years from UK Biobank (2006\u20132024). Cox proportional hazards regression models were employed to estimate ASCVD risk, with stratification by reproductive characteristics (age at menarche, age at menopause, and menopausal status) and age groups (\u226445, 46\u201355, &gt;55\u2009years). Mediation analysis was conducted to examine potential biological pathways through sex hormones, inflammatory markers, and lipid profiles. All analyses were adjusted for demographic factors, socioeconomic status, lifestyle factors, and reproductive history.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During follow\u2010up, 11\u2009357 women (6.67%) developed ASCVD. HRT users demonstrated elevated ASCVD risk (adjusted HR 1.13, 95% CI 1.08\u20131.18,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), primarily from increased ischemic stroke. Risk varied by reproductive characteristics: late menarche showed highest risk (HR 1.15, 95% CI 1.08\u20131.24), followed by late menopause (HR 1.25, 95% CI 1.01\u20131.54). Perimenopause demonstrated the most pronounced elevation (HR 1.28, 95% CI 1.12\u20131.46). Women \u226445\u2009years had 77% higher ASCVD risk with HRT use. Dose\u2013response relationships between HRT duration (\u22655\u2009years) and ASCVD risk were observed (\n                      <jats:italic>p<\/jats:italic>\n                      <jats:sub>overall<\/jats:sub>\n                      \u2009=\u20090.009,\n                      <jats:italic>p<\/jats:italic>\n                      <jats:sub>nonlinear<\/jats:sub>\n                      \u2009=\u20090.004). Mediation analysis revealed minimal indirect effects through traditional biomarkers (&lt;2%), suggesting direct vascular mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HRT increases ASCVD risk with substantial variation by reproductive characteristics. Findings support reproductive profile\u2010based cardiovascular risk assessment for personalized HRT prescribing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aogs.70316","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T08:20:50Z","timestamp":1787214050000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elevated cardiovascular risk associated with hormone replacement therapy: A comprehensive analysis of reproductive factors and atherosclerotic cardiovascular disease outcomes in the\n                    <scp>UK<\/scp>\n                    Biobank cohort"],"prefix":"10.1111","author":[{"given":"Mengchun","family":"Wang","sequence":"first","affiliation":[{"name":"School of Public Health, Department of Medicine Xi'an Jiaotong University  Xi'an Shaanxi 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