{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:07:00Z","timestamp":1787018820533,"version":"build-2736575974"},"reference-count":56,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"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":["Cephalalgia"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Many guidelines list migraine with aura (MwA) as a contraindication to estrogen-containing combined hormonal contraceptives (CHCs) due to vascular risks. However, current evidence is based on small sample studies with potential influence by confounding factors. Additionally, few studies have examined the vascular risk associated with modern CHCs with lower dose estrogen, particularly in relation to aura status. The present study aims to investigate the vascular risk of modern CHCs in women with migraine with and without aura.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used a de-identified electronic medical record database with 120 million patients across multiple health systems in the United States of America. We included female patients aged 18\u201345 years who received a migraine diagnosis code, had at least three office visits within three years, and were prescribed at least one migraine-specific medication within 6 months following the first outpatient visit. All data after 2010 were included. Patients with prior cardiovascular events were excluded. Our composite endpoint consisted of acute ischemic stroke, acute myocardial infarction, deep vein thrombosis\/pulmonary embolism and intravenous thrombolytic administration. We stratified our analysis according to CHC exposure and aura status and compared the incidence of the endpoint with high-dimensional propensity score-matching between CHC users and non-users in (i) the overall cohort, (ii) MwA and (iii) migraine without aura (MwoA); between MwA and MwoA in (iv) patients prescribed CHCs; and in (v) those without CHC prescriptions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We included 5535 patients who received CHC prescriptions and 21,520 who did not. 114 (2.06%) of CHC users and 547 (2.54%) of CHC non-users had at least one vascular event. With propensity score-matched comparison, the composite endpoint did not significantly differ between CHC and non-CHC in the overall migraine group, those with MwA and the MwoA group. In those prescribed CHC, MwA and MwoA did not differ in all the outcomes. For CHC non-users, MwA was associated with a higher incidence of acute ischemic stroke (hazard ratio = 2.45; 95% confidence interval = 1.58\u20133.78;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.001;\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20096201 in each group) and the composite endpoint (hazard ratio = 1.34; 95% confidence interval = 1.08\u20131.67;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.008).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our real-world study showed that exposure to modern CHC was not associated with a significant increase in vascular risk in women aged 18\u201345 years with migraine, MwA or MwoA who have no prior cardiovascular events. However, in those who never received CHC, MwA was associated with higher vascular risks compared to MwoA. While limitations exist using large scale electronic medical record databases for analysis, our results suggest that carefully designed prospective studies should be conducted to reassess the vascular risk associated with CHC use in women with migraine, especially MwA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03331024251404924","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T18:16:07Z","timestamp":1765995367000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Estrogen exposure from modern contraceptives and vascular risk in women with migraine: A nationwide electronic medical record database study"],"prefix":"10.1177","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5644-0468","authenticated-orcid":false,"given":"Keiko","family":"Ihara","sequence":"first","affiliation":[{"name":"Mayo Clinic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. William","family":"Pike","sequence":"additional","affiliation":[{"name":"Atropos Health, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Hui","sequence":"additional","affiliation":[{"name":"Atropos Health, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurabh","family":"Gombar","sequence":"additional","affiliation":[{"name":"Atropos Health, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Atropos Health, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Callahan","sequence":"additional","affiliation":[{"name":"Atropos Health, New York, NY, USA"},{"name":"Stanford University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gretchen E.","family":"Tietjen","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Toledo, Toledo, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7802-7172","authenticated-orcid":false,"given":"Chia-Chun","family":"Chiang","sequence":"additional","affiliation":[{"name":"Mayo Clinic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.14709"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1526-4610.2001.041007646.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2017.11.027"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.13796"},{"key":"e_1_3_2_6_2","article-title":"Low dose oestrogen combined oral contraception and risk of pulmonary embolism, stroke, and myocardial infarction in five million French women: cohort study","volume":"353","author":"Weill A","year":"2016","unstructured":"Weill A, Dalichampt M, Raguideau F, et al. Low dose oestrogen combined oral contraception and risk of pulmonary embolism, stroke, and myocardial infarction in five million French women: cohort study. Br Med J 2016; 353: i2002.","journal-title":"Br Med J"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-020498"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1004238"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.119.014546"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.12885"},{"key":"e_1_3_2_11_2","article-title":"Migraine and risk of cardiovascular diseases: Danish population based matched cohort study","volume":"360","author":"Adelborg K","year":"2018","unstructured":"Adelborg K, Szepligeti SK, Holland-Bill L, et al. Migraine and risk of cardiovascular diseases: Danish population based matched cohort study. Br Med J 2018; 360: k96.","journal-title":"Br Med J"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e3182994c43"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2012.09.015"},{"key":"e_1_3_2_14_2","volume-title":"Medical eligibility criteria for contraceptive use","author":"World Health Organization","year":"2015","unstructured":"World Health Organization. Medical eligibility criteria for contraceptive use. 5th ed. Geneva: World Health Organization, 2015.","edition":"5"},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","unstructured":"ACOG Practice bulletin No. 206: use of hormonal contraception in women with coexisting medical conditions. Obstet Gynecol 2019; 133: e128\u2013e150.","DOI":"10.1097\/AOG.0000000000003072"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000442009.06663.48"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-017-0815-1"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2016.12.019"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.rr7304a1"},{"key":"e_1_3_2_20_2","unstructured":"Healthcare. FoSaR. UK medical eligibility criteria for contraceptive use (UKMEC) 2019. 2019."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jogoh.2019.04.009"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-2982.2000.00035.x"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-018-0912-9"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.12960"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.13229"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2020.1730816"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.14473"},{"key":"e_1_3_2_28_2","volume-title":"A clinical guide for contraception","author":"Speroff L","year":"2011","unstructured":"Speroff L, Darney PD. A clinical guide for contraception. Lippincott Williams & Wilkins, 2011."},{"key":"e_1_3_2_29_2","article-title":"Combined oral contraceptives: the risk of myocardial infarction and ischemic stroke","volume":"2015","author":"Roach RE","year":"2015","unstructured":"Roach RE, Helmerhorst FM, Lijfering WM, et al. Combined oral contraceptives: the risk of myocardial infarction and ischemic stroke. Cochrane Database Syst Rev 2015; 2015: Cd011054.","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_3_2_30_2","first-page":"1","article-title":"Use of contraception and use of family planning services in the United States: 1982-2002","volume":"350","author":"Mosher WD","year":"2004","unstructured":"Mosher WD, Martinez GM, Chandra A, et al. Use of contraception and use of family planning services in the United States: 1982-2002. Adv Data 2004; 350: 1\u201336.","journal-title":"Adv Data"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0043-1764382"},{"key":"e_1_3_2_32_2","first-page":"1","article-title":"Current contraceptive Status among women aged 15-49: United States, 2017-2019","volume":"388","author":"Daniels K","year":"2020","unstructured":"Daniels K, Abma JC. Current contraceptive Status among women aged 15-49: United States, 2017-2019. NCHS Data Brief 2020; 388:1\u20138.","journal-title":"NCHS Data Brief"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-001-0089-8"},{"key":"e_1_3_2_34_2","unstructured":"Atropos Health. Atropos health's evidence network. https:\/\/www.atroposhealth.com\/atropos-evidence-network\/ (accessed 5 December 2025)."},{"key":"e_1_3_2_35_2","author":"WHO Collaborating Centre for Drug Statistics Methodology","unstructured":"WHO Collaborating Centre for Drug Statistics Methodology. Guidelines for ATC classification and DDD assignment. Oslo, Norway: WHO Collaborating Centre for Drug Statistics Methodology. https:\/\/www.whocc.no\/atc_ddd_index\/.","journal-title":"Guidelines for ATC classification and DDD assignment"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1136\/amiajnl-2011-000116"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-024-19551-1"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9681(87)90171-8"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.mlr.0000182534.19832.83"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e3181a663cc"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwv108"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15636"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.06.010"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12051935"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.29.11.2277"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.38302.504063.8F"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b3914"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2009.12.021"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-016-2746-z"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/5523516"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-017-0152-8"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.182279"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.488395"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2021.106067"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1177\/0333102417698936"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.121.038659"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2024.2044"}],"container-title":["Cephalalgia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03331024251404924","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/03331024251404924","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03331024251404924","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:46:43Z","timestamp":1777387603000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/03331024251404924"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":56,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1177\/03331024251404924"],"URL":"https:\/\/doi.org\/10.1177\/03331024251404924","relation":{},"ISSN":["0333-1024","1468-2982"],"issn-type":[{"value":"0333-1024","type":"print"},{"value":"1468-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"article-number":"03331024251404924"}}