{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T19:08:08Z","timestamp":1770404888968,"version":"3.49.0"},"update-to":[{"DOI":"10.1371\/journal.pmed.1004652","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000}}],"reference-count":21,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sygeforsikringen \u201cDanmark\u201d","award":["grant 2021-0128"],"award-info":[{"award-number":["grant 2021-0128"]}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sex hormones have been implicated in leukemogenesis, but evidence regarding hormonal contraceptive use and leukemia risk remains limited and primarily based on older formulations. Given the widespread use of contemporary hormonal contraceptives, clarification of this potential association is needed. This study examines the association between contemporary hormonal contraceptives and leukemia risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>\n                      In a nationwide cohort design, we assessed associations between the use of contemporary hormonal contraceptives and the risk of leukemia based on a cohort of all women aged 15\u201349 years residing in Denmark from 1995 to 2021 with no previous cancer, hysterectomy, oophorectomy, or sterilization. Information on hormonal contraception use, leukemia diagnoses, and potential confounders (age, calendar year, education) was obtained from nationwide registries. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals [CIs] were estimated for any leukemia, and specific types of leukemia, associated with any hormonal contraceptive use, current and recent use, and previous use, type of product used, duration, and time since last use. Among 1,957,490 pre-menopausal women followed for 24.5 million person-years (median 12.5 years, interquartile range: 5.9,20.5), 671 were diagnosed with leukemia. The incidence rate for leukemia among current and recent users was similar to that among women who had never used hormonal contraception: IRR 0.95 (95% CI [0.78,1.16];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.62). No association with different durations of use was found: 0\u20135 years; IRR 0.93 (95% CI [0.75,1.14];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.48),\u2009&gt;5\u201310 years; IRR 1.16 (95% CI [0.84,1.61];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.37),\u2009&gt;10 years; IRR 0.67 (95% CI [0.33,1.37];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.27); nor for time since last use: 0\u20135 years; IRR 1.01 (95% CI [0.78,1.29];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.96),\u2009&gt;5\u201310 years; IRR 1.05 (95% CI [0.76,1.45];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.75),\u2009&gt;10 years; IRR 0.88 (95% CI [0.60,1.29];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.52). Also, the IRRs for leukemia with use of different hormonal contraceptive types (e.g., combined products; IRR 0.91 (95% CI [0.73,1.14];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.42) and progestin-only products; IRR 1.05 (95% CI [0.78,1.40];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.75)), as well as for product-specific durations of use, were for the majority close to 1. The IRRs were similar for different types of leukemia. Main study limitations include small case numbers in some analyses; therefore, additional large-scale studies are warranted to reliably exclude weak associations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Contemporary hormonal contraceptives were not associated with leukemia, independent of product used, duration of use, time since last use, and type of leukemia. While estimates were imprecise for some subgroups, the overall findings do not support an association.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1004652","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T18:44:31Z","timestamp":1769798671000},"page":"e1004652","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Leukemia in users of contemporary hormonal contraception: A nationwide registry-based cohort study among premenopausal women in Denmark"],"prefix":"10.1371","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5420-1981","authenticated-orcid":true,"given":"Caroline H.","family":"Hemmingsen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne K.","family":"Kjaer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8644-0822","authenticated-orcid":true,"given":"Jasmin","family":"Arvedsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8970-7226","authenticated-orcid":true,"given":"Emma O.","family":"Dahl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amani","family":"Meaidi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6821-9242","authenticated-orcid":true,"given":"Marie","family":"Hargreave","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6506-2569","authenticated-orcid":true,"given":"Lina S.","family":"M\u00f8rch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"pmed.1004652.ref001","article-title":"Disease burden, risk factors, and trends of leukaemia: a global analysis","volume":"12","author":"J Huang","year":"2022","journal-title":"Front Oncol"},{"key":"pmed.1004652.ref002","volume-title":"NORDCAN: cancer incidence, mortality, prevalence and survival in the Nordic countries, Version 9.3 (02.10.2023)","author":"SAG Lar\u00f8nningen","year":"2023"},{"issue":"6","key":"pmed.1004652.ref003","article-title":"Epidemiology and etiology of leukemia and lymphoma","volume":"10","author":"JAB Bispo","year":"2020","journal-title":"Cold Spring Harb Perspect Med"},{"issue":"5","key":"pmed.1004652.ref004","first-page":"483","article-title":"Hormone replacement therapy is not associated with an increased risk of leukemia (United States)","volume":"16","author":"JA Ross","year":"2005","journal-title":"Cancer Causes Control"},{"issue":"4","key":"pmed.1004652.ref005","doi-asserted-by":"crossref","first-page":"907","DOI":"10.3390\/cancers12040907","article-title":"Estrogen receptors alpha and beta in acute myeloid leukemia","volume":"12","author":"A Roma","year":"2020","journal-title":"Cancers (Basel)"},{"issue":"6","key":"pmed.1004652.ref006","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/ijc.2910270602","article-title":"Androgen, estrogen and progestin binding sites in human leukemic cells","volume":"27","author":"L Danel","year":"1981","journal-title":"Int J Cancer"},{"issue":"3","key":"pmed.1004652.ref007","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.18632\/oncotarget.6698","article-title":"Novel evidence that pituitary gonadotropins directly stimulate human leukemic cells-studies of myeloid cell lines and primary patient AML and CML cells","volume":"7","author":"A Abdelbaset-Ismail","year":"2016","journal-title":"Oncotarget"},{"key":"pmed.1004652.ref008","doi-asserted-by":"crossref","first-page":"115168","DOI":"10.1016\/j.ejca.2024.115168","article-title":"Maternal use of hormonal contraception and risk of childhood leukemia: a Scandinavian population-based cohort study","volume":"215","author":"CH Hemmingsen","year":"2025","journal-title":"Eur J Cancer"},{"issue":"7484","key":"pmed.1004652.ref009","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/nature12932","article-title":"Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy","volume":"505","author":"D Nakada","year":"2014","journal-title":"Nature"},{"key":"pmed.1004652.ref010","unstructured":"United Nations Department of Economic and Social Affairs. World Family Planning 2022: Meeting the changing needs for family planning: contraceptive use by age and method. [cited 15 Mar 2025]. Available from: https:\/\/www.un.org\/development\/desa\/pd\/sites\/www.un.org.development.desa.pd\/files\/files\/documents\/2023\/Feb\/undesa_pd_2022_world-family-planning.pdf"},{"issue":"6","key":"pmed.1004652.ref011","article-title":"Hormonal contraceptive use in Denmark 2010-2019","volume":"68","author":"SI Kristensen","year":"2021","journal-title":"Dan Med J"},{"issue":"2","key":"pmed.1004652.ref012","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/(SICI)1099-1557(199803\/04)7:2<113::AID-PDS329>3.0.CO;2-9","article-title":"Drug use and acute leukemia","volume":"7","author":"G Traversa","year":"1998","journal-title":"Pharmacoepidemiol Drug Saf"},{"issue":"7","key":"pmed.1004652.ref013","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1038\/bjc.2013.507","article-title":"Exogenous hormone use, reproductive history and risk of adult myeloid leukaemia","volume":"109","author":"JN Poynter","year":"2013","journal-title":"Br J Cancer"},{"issue":"8","key":"pmed.1004652.ref014","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1093\/aje\/kwx388","article-title":"Oral contraceptive use and risks of cancer in the NIH-AARP diet and health study","volume":"187","author":"KA Michels","year":"2018","journal-title":"Am J Epidemiol"},{"key":"pmed.1004652.ref015","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1097\/AOG.0000000000000356","article-title":"Cancer risk in women using the levonorgestrel-releasing intrauterine system in Finland","volume":"124","author":"T Soini","year":"2014","journal-title":"Obstet Gynecol"},{"issue":"8","key":"pmed.1004652.ref016","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s10654-014-9930-3","article-title":"The Danish Civil Registration System as a tool in epidemiology","volume":"29","author":"M Schmidt","year":"2014","journal-title":"Eur J Epidemiol"},{"key":"pmed.1004652.ref017","doi-asserted-by":"crossref","first-page":"449","DOI":"10.2147\/CLEP.S91125","article-title":"The Danish National Patient Registry: a review of content, data quality, and research potential","volume":"7","author":"M Schmidt","year":"2015","journal-title":"Clin Epidemiol"},{"key":"pmed.1004652.ref018","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1177\/1403494810394717","article-title":"The Danish National Prescription Registry","volume":"39","author":"HW Kildemoes","year":"2011","journal-title":"Scand J Public Health"},{"key":"pmed.1004652.ref019","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1177\/1403494810393562","article-title":"The Danish Cancer Registry","volume":"39","author":"ML Gjerstorff","year":"2011","journal-title":"Scand J Public Health"},{"issue":"1","key":"pmed.1004652.ref020","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s10654-018-0356-1","article-title":"The Danish Medical Birth Register","volume":"33","author":"M Bliddal","year":"2018","journal-title":"Eur J Epidemiol"},{"issue":"5","key":"pmed.1004652.ref021","doi-asserted-by":"crossref","first-page":"725","DOI":"10.3109\/02841861003782017","article-title":"NORDCAN\u2014a Nordic tool for cancer information, planning, quality control and research","volume":"49","author":"G Engholm","year":"2010","journal-title":"Acta Oncol"}],"updated-by":[{"DOI":"10.1371\/journal.pmed.1004652","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000}}],"container-title":["PLOS Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004652","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T18:55:51Z","timestamp":1770317751000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004652"}},"subtitle":[],"editor":[{"given":"Suzanne C.","family":"Cannegieter","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":21,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pmed.1004652","relation":{},"ISSN":["1549-1676"],"issn-type":[{"value":"1549-1676","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,30]]}}}