{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T02:13:36Z","timestamp":1780625616782,"version":"3.54.1"},"reference-count":34,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002794","name":"Swedish Cancer Society","doi-asserted-by":"publisher","award":["21 0447\u00a0FE"],"award-info":[{"award-number":["21 0447\u00a0FE"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002794","name":"Swedish Cancer Society","doi-asserted-by":"publisher","award":["19 0383 Pj"],"award-info":[{"award-number":["19 0383 Pj"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2019-01497"],"award-info":[{"award-number":["2019-01497"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Marcus Borgstr\u00f6m Foundation"},{"name":"Hedstr\u00f6ms Foundation"},{"DOI":"10.13039\/100007435","name":"\u00c5ke Wiberg Foundation","doi-asserted-by":"publisher","award":["M19-0349\/M20-0057"],"award-info":[{"award-number":["M19-0349\/M20-0057"]}],"id":[{"id":"10.13039\/100007435","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Rudbergs Foundation"},{"name":"Vleugels Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>High levels of estrogen are associated with increased risk of breast and endometrial cancer and have been suggested to also play a role in the development of ovarian cancer. Cancerogenic effects of estradiol, the most prominent form of estrogen, have been highlighted as a side effect of estrogen-only menopausal hormone therapy. However, whether high levels of endogenous estrogens, produced within the body, promote cancer development, has not been fully established.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We aimed to examine causal effects of estradiol on breast, endometrial, and ovarian cancer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Here we performed a two-sample Mendelian randomization (MR) to estimate the effect of endogenous estradiol on the risk of developing breast, endometrial, and ovarian cancer, using the UK Biobank as well as 3 independent cancer cohorts.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Using 3 independent instrumental variables, we showed that higher estradiol levels significantly increase the risk for ovarian cancer (OR\u2005=\u20053.18 [95% CI, 1.47-6.87], P\u2005=\u20050.003). We also identified a nominally significant effect for ER-positive breast cancer (OR\u2005=\u20052.16 [95% CI, 1.09-4.26], P\u2005=\u20050.027). However, we could not establish a clear link to the risk of endometrial cancer (OR\u2005=\u20051.93 [95% CI, 0.77-4.80], P\u2005=\u20050.160).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our results suggest that high estradiol levels promote the development of ovarian and ER-positive breast cancer.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jendso\/bvac100","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T12:20:17Z","timestamp":1656505217000},"source":"Crossref","is-referenced-by-count":47,"title":["Investigating the Effect of Estradiol Levels on the Risk of Breast, Endometrial, and Ovarian Cancer"],"prefix":"10.1210","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2915-4498","authenticated-orcid":false,"given":"\u00c5sa","family":"Johansson","sequence":"first","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University , 75108 Uppsala , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4480-891X","authenticated-orcid":false,"given":"Daniel","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University , 75108 Uppsala , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8061-3947","authenticated-orcid":false,"given":"Julia","family":"H\u00f6glund","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University , 75108 Uppsala , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Hadizadeh","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Science for Life 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