{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:42:31Z","timestamp":1780472551447,"version":"3.54.1"},"reference-count":52,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Differentiated thyroid carcinoma (DTC) is occurring three times more frequently in females than in males. However, the underlying biological mechanisms driving this discrepancy remain poorly understood. To investigate the causal role of sex hormones and reproductive factors in the risk of DTC, we implemented a two-sample Mendelian randomization (MR) analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We utilized genome-wide association studies (GWAS) summary statistics to explore these associations. GWAS data on DTC were derived from a meta-analysis of six studies including 7705 cases and 963,612 controls of European ancestry. GWAS summary statistics on sex hormones, reproductive factors, and gynecological conditions were retrieved from publicly available sources. We used the inverse-variance weighted (IVW) method to estimate odds ratio (OR), with additional sensitivity analyses and conducted multivariable MR (MVMR) to account for potential confounding by body mass index (BMI) and thyrotropin (TSH).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We identified a positive association between sex hormone binding globulin (SHBG) and DTC (OR\n                      <jats:sub>ivw<\/jats:sub>\n                      = 1.13,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.046). After controlling for TSH and BMI in a MVMR analysis, the strength of this association remained similar but lost statistical significance. Bioavailable testosterone also showed a positive but marginally significant association with DTC after adjustment for BMI in the MVMR (OR\n                      <jats:sub>ivw<\/jats:sub>\n                      = 1.13,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.07). Putative causal association was observed with uterine fibroids in females under 50 years old (OR\n                      <jats:sub>ivw<\/jats:sub>\n                      = 1.52,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.017). Endometrial cancer was associated with DTC (OR\n                      <jats:sub>ivw<\/jats:sub>\n                      = 1.15,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 9.0 \u00d7 10\n                      <jats:sup>\u22123<\/jats:sup>\n                      ); however, a genetic correlation of r\n                      <jats:sup>2<\/jats:sup>\n                      = 13% suggested potential pleiotropy. No significant associations were observed for other investigated factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our study does not provide strong evidence for a causal role of reproductive and hormonal factors in DTC risk, despite the observed sex disparity in incidence rates. The associations observed with SHBG, bioavailable testosterone, uterine fibroids, and endometrial cancer indicate potential risk factors, but further investigation is required.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2024.0548","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T12:01:14Z","timestamp":1742990474000},"page":"433-443","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Reproductive Factors, Sex Hormone Levels, and Differentiated Thyroid Cancer Risk: A Mendelian Randomization Study"],"prefix":"10.1177","volume":"35","author":[{"given":"See Hyun","family":"Park","sequence":"first","affiliation":[{"name":"UVSQ, Inserm, Gustave Roussy, CESP, Paris-Saclay University, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Emmanuel","family":"Sugier","sequence":"additional","affiliation":[{"name":"UVSQ, Inserm, Gustave Roussy, CESP, Paris-Saclay University, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazdan","family":"Asgari","sequence":"additional","affiliation":[{"name":"UVSQ, Inserm, Gustave Roussy, CESP, Paris-Saclay University, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojgan","family":"Karimi","sequence":"additional","affiliation":[{"name":"UVSQ, Inserm, Gustave Roussy, CESP, Paris-Saclay University, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Kaaks","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9e Turzanski","family":"Fortner","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany."},{"name":"Department of Research, Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Schulze","sequence":"additional","affiliation":[{"name":"Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Agnoli","sequence":"additional","affiliation":[{"name":"Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Pasanisi","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University Hospital, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlotta","family":"Sacerdote","sequence":"additional","affiliation":[{"name":"Citt\u00e0 della Salute e della Scienza di Torino Hospital, Turin, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Rodriguez-Barranco","sequence":"additional","affiliation":[{"name":"Escuela Andaluza de Salud P\u00fablica (EASP), Granada, Spain."},{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, Granada, Spain."},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Epidemiolog\u00eda y Salud P\u00fablica (CIBERESP), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaia","family":"Aizpurua","sequence":"additional","affiliation":[{"name":"Sub Directorate for Public Health and Addictions of Gipuzkoa, Ministry of Health of the Basque Government, San Sebastian, Spain."},{"name":"Epidemiology of Chronic and Communicable Diseases Group, Biogipuzkoa Health Research Institute, San Sebasti\u00e1n, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Cabrera Castro","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Epidemiolog\u00eda y Salud P\u00fablica (CIBERESP), Madrid, Spain."},{"name":"Department of Epidemiology, Murcia Regional Health Council-IMIB, Murcia, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Guevara","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Epidemiolog\u00eda y Salud P\u00fablica (CIBERESP), Madrid, Spain."},{"name":"Instituto de Salud P\u00fablica y Laboral de Navarra, Pamplona, Spain."},{"name":"Navarra Institute for Health Research (IdiSNA), Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandar","family":"Tin Tin","sequence":"additional","affiliation":[{"name":"Cancer 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