{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:25:19Z","timestamp":1787505919233,"version":"build-2736575974"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>The combined hormonal contraceptive (CHC) with ethinylestradiol and progestins is the most widely used contraceptive method among young women and is used by millions worldwide. However, uncertainties exist about the risk of ischemic stroke associated with the use of CHCs with low-dose ethinylestradiol (&lt;50-\u00b5g ethinylestradiol) and with the newest fourth-generation progestins that have only been sparsely investigated for the risk of ischemic stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>In this cohort study based on Danish registries covering the entire Danish female population aged 18 to 49 years from 2004 to 2021, we investigated incidence rate ratios (IRRs) of ischemic stroke using CHCs compared with nonuse of hormonal contraceptives. Analyses focused on comparing CHCs based on ethinylestradiol content (30\u201340- versus \u226420-\u03bcg ethinylestradiol), progestin generation (second, third, and fourth) in CHCs, and route of administration (monophasic versus sequential). Poisson regression models adjusting for age, education, ethnicity, calendar year, and medication used for risk factors were utilized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>In total, 1\u2005711\u2005757 nonpregnant women contributed 14\u2005697\u2005788 person-years to the investigation. For users of CHCs containing &lt;50-\u00b5g ethinylestradiol, the adjusted IRR was increased by 1.77 (95% CI, 1.62\u20131.93) compared with nonusers of hormonal contraceptives. IRR did not differ between CHCs with 30- to 40- and \u226420-\u00b5g ethinylestradiol. Adjusted incidence rate difference between CHC users and nonusers of hormonal contraceptives ranged from 1 in 100\u2005000 women per year in 18 to 24 years of age to 24 in 100\u2005000 women per year in \u226545 years of age. Incidence rate in users of fourth-generation CHCs was 30% lower than that of second-generation CHCs adjusted IRR (0.70 [95% CI, 0.50\u20130.98]). IRR for users of third-generation CHCs did not differ significantly from that of second-generation users adjusted IRR (1.14 [95% CI, 0.97\u20131.35]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Use of CHCs was associated with a 1.77 higher IRR of ischemic stroke. IRR did not relate to ethinylestradiol content in users of CHCs with &lt;50-\u00b5g ethinylestradiol. IRR was 30% lower in users of fourth-generation than in users of second-generation CHCs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.124.049252","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T05:04:21Z","timestamp":1733720661000},"page":"276-284","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Ischemic Stroke in Users of Combined Hormonal Contraceptives: A Danish Registry Study"],"prefix":"10.1161","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3817-5430","authenticated-orcid":true,"given":"Gasper","family":"Letnar","sequence":"first","affiliation":[{"name":"Omicron ApS, Copenhagen, Telefonvej 8d 2860 S\u00f8borg, Denmark (G.L., K.K.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3573-092X","authenticated-orcid":true,"given":"Klaus Kaae","family":"Andersen","sequence":"additional","affiliation":[{"name":"Omicron ApS, Copenhagen, Telefonvej 8d 2860 S\u00f8borg, Denmark (G.L., K.K.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7462-4789","authenticated-orcid":true,"given":"Tom Skyh\u00f8j","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Bispebjerg University Hospital, Bispebjerg bakke 23, Copenhagen, Denmark (T.S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/aogs.13055"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1111840"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2015.04.021"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD011054.pub2"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i2002"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.284.1.72"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.164.7.741"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-1958"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S103662"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1177\/1403494811399956"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/1403494810394717"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.20.10.1407"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011636"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1159\/000102143"},{"key":"e_1_3_3_16_2","unstructured":"Dansk Stroke Register. National \u00e5rsrapport 2022. Accessed February 22 2024. https:\/\/www.sundhed.dk\/content\/cms\/69\/4669_danstroke_aarsrapport-2022_offentlig-version_201130.pdf"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S50449"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d6423"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.2014.950654"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjsrh-2018-CHC"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00993"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2016.01.012"},{"key":"e_1_3_3_23_2","unstructured":"Combined hormonal contraceptives \u2013 referral. Accessed August 26 2024. https:\/\/www.ema.europa.eu\/en\/medicines\/human\/referrals\/combined-hormonal-contraceptives"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e3182a5ec6b"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000762"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.124.047438"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.004601"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1177\/2396987317706600"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.124.049252","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T11:52:01Z","timestamp":1743076321000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.124.049252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":27,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1161\/STROKEAHA.124.049252"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.124.049252","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"2024-09-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-22","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}