{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T16:34:13Z","timestamp":1767371653357,"version":"3.48.0"},"reference-count":47,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Stress and its psychiatric consequences\u2014including depression, anxiety, and posttraumatic stress disorder (PTSD)\u2014are pertinent to women\u2019s cardiovascular health, but research on intersections with relevant sex-specific factors (eg, hormonal contraceptives) is lacking.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To examine whether stress-related psychiatric diagnoses moderate associations between hormonal contraceptive use and cardiovascular and thrombotic risk.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This retrospective cohort study included electronic health record data collected from a US hospital-based biobank and analyzed from May 2, 2024, to November 3, 2025. Participants were women aged 18 to 55 years who consented into the biobank before or on September 12, 2020.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n \n Lifetime history of stress-related psychiatric disorders, including depression (major depressive disorder), anxiety (generalized anxiety disorder, social anxiety disorder, or panic disorder), and PTSD, defined by\n International Statistical Classification of Diseases and Related Health Problems, Tenth Revision<\/jats:italic>\n (\n ICD-10<\/jats:italic>\n ) codes and analyzed as separate diagnoses, and lifetime history of combined hormonal contraceptive use, defined by RxNorm codes.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n \n The primary outcomes were major adverse cardiovascular events (MACE; defined as\n ICD-10<\/jats:italic>\n codes for infarction, unstable angina, heart failure, coronary revascularization, peripheral vascular disease, peripheral revascularization, stroke, and\/or transient ischemic attack) and deep-vein thrombosis (DVT). Three 2-step hierarchical logistic regressions per outcome were conducted.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n In this sample of 31\u202f824 women (mean [SD] age, 38.5 [10.6] years), over one-third (11\u202f950 women [37.6%]) had hormonal contraceptive use history, and stress-related disorders were common (depression, 9116 women [28.5%]; anxiety, 3533 women [11.1%]; PTSD, 1992 women [6.3%]). Associations were mixed across the stress-related disorders, in that depression and anxiety did not moderate associations between contraceptive use and MACE or DVT. In contrast, PTSD modified the association between contraceptive use and MACE but not that between contraceptive use and DVT. Analyses stratified by PTSD status found that only women without PTSD using contraceptives had lower odds for MACE (odds ratio, 0.69; 95% CI, 0.87-3.24). The odds ratio for MACE among women with PTSD was greater than 1, but the finding was not statistically significant (odds ratio, 1.68; 95% CI, 0.87-3.24).<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this retrospective cohort study, combined hormonal contraceptive use was associated with lower cardiovascular risk in women regardless of depression or anxiety. These protective associations did not extend to women with PTSD, suggesting that there are unique cardiovascular processes in the context of this stress-related disorder and hormonal contraceptive use that warrant further research.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.51878","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T16:30:55Z","timestamp":1767371455000},"page":"e2551878","source":"Crossref","is-referenced-by-count":0,"title":["Hormonal Contraceptive Use, Stress Disorders, and Cardiovascular and Thrombotic Risk in Women"],"prefix":"10.1001","volume":"9","author":[{"given":"Jordan L.","family":"Thomas","sequence":"first","affiliation":[{"name":"Behavioral Science Division, National Center for PTSD, VA Boston Healthcare System, Boston, Massachusetts"},{"name":"Department of Psychiatry, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts"},{"name":"Department of Psychology, University of Kansas, Lawrence"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robyn A.","family":"Ellis","sequence":"additional","affiliation":[{"name":"McLean Hospital, Belmont, Massachusetts"},{"name":"Department of Psychiatry, Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krystel","family":"AbiKaram","sequence":"additional","affiliation":[{"name":"Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shady","family":"Abohashem","sequence":"additional","affiliation":[{"name":"Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anahita","family":"Dua","sequence":"additional","affiliation":[{"name":"Vascular Center, Massachusetts General Hospital, Boston"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily S.","family":"Lau","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen J.","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen K.","family":"Miller","sequence":"additional","affiliation":[{"name":"Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne L.","family":"Pineles","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts"},{"name":"Women\u2019s Health Sciences Division, National Center for PTSD, VA Boston Healthcare System, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel P.","family":"Rosovsky","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Tawakol","sequence":"additional","affiliation":[{"name":"Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael T.","family":"Osborne","sequence":"additional","affiliation":[{"name":"Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston"},{"name":"Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia V.","family":"Seligowski","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Harvard Medical School, Boston, Massachusetts"},{"name":"Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"10","published-online":{"date-parts":[[2026,1,2]]},"reference":[{"issue":"1","key":"zoi251383r1","first-page":"65","article-title":"Matters of the heart: cardiovascular disease in U.S. women.","volume":"110","author":"Bybee","year":"2013","journal-title":"Mo Med"},{"issue":"5","key":"zoi251383r2","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.jacc.2004.12.005","article-title":"The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: the emerging field of behavioral cardiology.","volume":"45","author":"Rozanski","year":"2005","journal-title":"J Am Coll Cardiol"},{"issue":"10","key":"zoi251383r3","doi-asserted-by":"publisher","first-page":"e763","DOI":"10.1161\/CIR.0000000000000947","article-title":"Psychological health, well-being, and the mind-heart-body connection: a scientific statement from the American Heart Association.","volume":"143","author":"Levine","year":"2021","journal-title":"Circulation"},{"issue":"3","key":"zoi251383r4","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.janxdis.2010.11.010","article-title":"Prevalence and axis I comorbidity of full and partial posttraumatic stress disorder in the United States: results from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions.","volume":"25","author":"Pietrzak","year":"2011","journal-title":"J Anxiety Disord"},{"issue":"11","key":"zoi251383r5","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1093\/ajh\/hpv047","article-title":"State of the art review: depression, stress, anxiety, and cardiovascular disease.","volume":"28","author":"Cohen","year":"2015","journal-title":"Am J Hypertens"},{"issue":"8","key":"zoi251383r6","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1161\/CIRCRESAHA.116.307547","article-title":"Cardiovascular disease in women: clinical perspectives.","volume":"118","author":"Garcia","year":"2016","journal-title":"Circ Res"},{"issue":"1","key":"zoi251383r7","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s12265-019-09906-0","article-title":"Sex-specific aspects in the pathophysiology and imaging of coronary macro- and microvascular disease.","volume":"13","author":"Groepenhoff","year":"2020","journal-title":"J Cardiovasc Transl Res"},{"issue":"5","key":"zoi251383r8","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1067\/mhj.2001.114198","article-title":"Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: results from the NHLBI WISE study.","volume":"141","author":"Reis","year":"2001","journal-title":"Am Heart J"},{"issue":"2","key":"zoi251383r9","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1177\/1358863X16686410","article-title":"Alternative causes of myocardial ischemia in women: an update on spontaneous coronary artery dissection, vasospastic angina and coronary microvascular dysfunction.","volume":"22","author":"Ahmed","year":"2017","journal-title":"Vasc Med"},{"issue":"3","key":"zoi251383r11","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/nrneph.2017.189","article-title":"Sex-specific differences in hypertension and associated cardiovascular disease.","volume":"14","author":"Colafella","year":"2018","journal-title":"Nat Rev Nephrol"},{"key":"zoi251383r12","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.thromres.2018.09.056","article-title":"Impact of sex, age, and risk factors for venous thromboembolism on the initial presentation of first isolated symptomatic acute deep vein thrombosis.","volume":"173","author":"Barco","year":"2019","journal-title":"Thromb Res"},{"issue":"10","key":"zoi251383r13","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1111\/jth.12678","article-title":"Differential risks in men and women for first and recurrent venous thrombosis: the role of genes and environment.","volume":"12","author":"Roach","year":"2014","journal-title":"J Thromb Haemost"},{"key":"zoi251383r14","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.thromres.2018.10.025","article-title":"Sex-specific differences in the distal versus proximal presenting location of acute deep vein thrombosis.","volume":"172","author":"Trinchero","year":"2018","journal-title":"Thromb Res"},{"key":"zoi251383r15","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.yfrne.2017.04.001","article-title":"Sex differences in cardiovascular disease: impact on care and outcomes.","volume":"46","author":"Humphries","year":"2017","journal-title":"Front Neuroendocrinol"},{"issue":"5","key":"zoi251383r17","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1080\/13697137.2019.1622085","article-title":"Impact of endogenous and exogenous progesterone exposure on stress biomarkers: a systematic review.","volume":"22","author":"Stadler","year":"2019","journal-title":"Climacteric"},{"issue":"7198","key":"zoi251383r18","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.1136\/bmj.318.7198.1579","article-title":"Oral contraceptives and myocardial infarction: results of the MICA case-control study.","volume":"318","author":"Dunn","year":"1999","journal-title":"BMJ"},{"issue":"7121","key":"zoi251383r19","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1136\/bmj.315.7121.1502","article-title":"Case-control study of oral contraceptives and risk of thromboembolic stroke: results from International Study on Oral Contraceptives and Health of Young Women.","volume":"315","author":"Heinemann","year":"1997","journal-title":"BMJ"},{"key":"zoi251383r20","doi-asserted-by":"publisher","first-page":"b2890","DOI":"10.1136\/bmj.b2890","article-title":"Hormonal contraception and risk of venous thromboembolism: national follow-up study.","volume":"339","author":"Lidegaard","year":"2009","journal-title":"BMJ"},{"issue":"2","key":"zoi251383r21","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.fertnstert.2006.11.206","article-title":"A prospective study of oral contraceptive use and risk of myocardial infarction among Swedish women.","volume":"88","author":"Margolis","year":"2007","journal-title":"Fertil Steril"},{"issue":"2","key":"zoi251383r22","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1002\/ajh.21059","article-title":"Smoking increases the risk of venous thrombosis and acts synergistically with oral contraceptive use.","volume":"83","author":"Pomp","year":"2008","journal-title":"Am J Hematol"},{"issue":"16","key":"zoi251383r23","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.030105","article-title":"Associations of oral contraceptive use with cardiovascular disease and all-cause death: evidence from the UK Biobank Cohort Study.","volume":"12","author":"Dou","year":"2023","journal-title":"J Am Heart Assoc"},{"issue":"3","key":"zoi251383r24","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.jacc.2008.09.042","article-title":"Contraceptive hormone use and cardiovascular disease.","volume":"53","author":"Shufelt","year":"2009","journal-title":"J Am Coll Cardiol"},{"issue":"1","key":"zoi251383r25","doi-asserted-by":"publisher","first-page":"H77","DOI":"10.1152\/ajpheart.00614.2020","article-title":"Influence of hormonal contraceptives on peripheral vascular function and structure in premenopausal females: a review.","volume":"320","author":"Williams","year":"2021","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"zoi251383r26","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.thromres.2018.03.005","article-title":"Systematic review and meta-analysis of the association of combined oral contraceptives on the risk of venous thromboembolism: the role of the progestogen type and estrogen dose.","volume":"165","author":"Oedingen","year":"2018","journal-title":"Thromb Res"},{"issue":"8","key":"zoi251383r27","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1177\/10815589231184227","article-title":"Harms of third- and fourth-generation combined oral contraceptives in premenopausal women: a systematic review and meta-analysis.","volume":"71","author":"Flores-Rodriguez","year":"2023","journal-title":"J Investig Med"},{"issue":"15","key":"zoi251383r28","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1001\/jama.2024.28778","article-title":"Contemporary hormonal contraception and risk of venous thromboembolism.","volume":"333","author":"Yonis","year":"2025","journal-title":"JAMA"},{"issue":"4","key":"zoi251383r29","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1097\/00006842-200107000-00011","article-title":"A meta-analytic examination of basal cardiovascular activity in posttraumatic stress disorder.","volume":"63","author":"Buckley","year":"2001","journal-title":"Psychosom Med"},{"issue":"5","key":"zoi251383r31","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.13014","article-title":"Incidence and progression of alcohol-associated liver disease after medical therapy for alcohol use disorder.","volume":"5","author":"Vannier","year":"2022","journal-title":"JAMA Netw Open"},{"issue":"2","key":"zoi251383r32","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1007\/s12350-022-03003-7","article-title":"The combined effect of air and transportation noise pollution on atherosclerotic inflammation and risk of cardiovascular disease events.","volume":"30","author":"Osborne","year":"2023","journal-title":"J Nucl Cardiol"},{"key":"zoi251383r33","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.bbi.2024.01.006","article-title":"PTSD increases risk for major adverse cardiovascular events through neural and cardio-inflammatory pathways.","volume":"117","author":"Seligowski","year":"2024","journal-title":"Brain Behav Immun"},{"issue":"4","key":"zoi251383r36","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1002\/sim.4067","article-title":"Multiple imputation using chained equations: issues and guidance for practice.","volume":"30","author":"White","year":"2011","journal-title":"Stat Med"},{"issue":"6","key":"zoi251383r37","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.biopsych.2010.09.013","article-title":"Fear extinction in traumatized civilians with posttraumatic stress disorder: relation to symptom severity.","volume":"69","author":"Norrholm","year":"2011","journal-title":"Biol Psychiatry"},{"issue":"2 Pt 2","key":"zoi251383r38","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.ijpsycho.2014.11.005","article-title":"Fear load: the psychophysiological over-expression of fear as an intermediate phenotype associated with trauma reactions.","volume":"98","author":"Norrholm","year":"2015","journal-title":"Int J Psychophysiol"},{"issue":"1","key":"zoi251383r39","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1017\/S0033291718003914","article-title":"Not all posttraumatic stress disorder symptoms are equal: fear, dysphoria, and risk of developing hypertension in trauma-exposed women.","volume":"50","author":"Sumner","year":"2020","journal-title":"Psychol Med"},{"issue":"2","key":"zoi251383r40","doi-asserted-by":"publisher","DOI":"10.1080\/20008066.2023.2282003","article-title":"Effects of oral contraceptives on intrusive memories: a secondary analysis of two studies using the trauma film paradigm in healthy women.","volume":"14","author":"Maslahati","year":"2023","journal-title":"Eur J Psychotraumatol"},{"key":"zoi251383r41","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.psyneuen.2017.10.006","article-title":"Neural activity during traumatic film viewing is linked to endogenous estradiol and hormonal contraception.","volume":"87","author":"Miedl","year":"2018","journal-title":"Psychoneuroendocrinology"},{"issue":"9","key":"zoi251383r42","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1101\/lm.053597.122","article-title":"Impact of hormonal contraceptives on sex differences in fear conditioning and fear extinction in PTSD.","volume":"29","author":"Bartholomew","year":"2022","journal-title":"Learn Mem"},{"issue":"3","key":"zoi251383r43","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1111\/j.1939-3938.2012.01134.x","article-title":"The influence of emergency contraception on post-traumatic stress symptoms following sexual assault.","volume":"8","author":"Ferree","year":"2012","journal-title":"J Forensic Nurs"},{"issue":"12","key":"zoi251383r44","doi-asserted-by":"publisher","first-page":"e71","DOI":"10.1016\/j.biopsych.2019.01.014","article-title":"Patterns of recovery from early posttraumatic stress symptoms after a preventive intervention with oxytocin: hormonal contraception use is a prognostic factor.","volume":"85","author":"Engel","year":"2019","journal-title":"Biol Psychiatry"},{"issue":"1","key":"zoi251383r45","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1186\/s12874-021-01416-5","article-title":"A narrative review on the validity of electronic health record-based research in epidemiology.","volume":"21","author":"Gianfrancesco","year":"2021","journal-title":"BMC Med Res Methodol"},{"key":"zoi251383r46","doi-asserted-by":"publisher","DOI":"10.1037\/ser0000969","article-title":"Assessing availability of depression severity indicators in electronic health record data: A retrospective study in two large academic health care systems in the United States.","author":"Anderson","year":"2025","journal-title":"Psychol Serv"},{"issue":"8","key":"zoi251383r47","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1038\/nrcardio.2015.83","article-title":"Epidemiology of venous thromboembolism.","volume":"12","author":"Heit","year":"2015","journal-title":"Nat Rev Cardiol"},{"key":"zoi251383r10","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/B978-0-12-822546-2.00019-8","volume-title":"The Vasculome","author":"Quyyumi","year":"2022"},{"key":"zoi251383r30","author":"von Elm"},{"key":"zoi251383r34","volume-title":"Applied Multiple Regression\/Correlation Analysis for the Behavioral Sciences","author":"Cohen","year":"2003","edition":"3rd ed"},{"key":"zoi251383r35","volume-title":"Methodological Issues and Strategies in Clinical Research","author":"Kazdin","year":"2024","edition":"5th ed"},{"key":"zoi251383r16","unstructured":"United Nations: Population Division. Contraceptive use by method 2019. December 31, 2019. Accessed May 4, 2024. https:\/\/www.un.org\/development\/desa\/pd\/content\/contraceptive-use-method-2019"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2843285\/thomas_2026_oi_251383_1766426068.28762.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T16:30:57Z","timestamp":1767371457000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2843285"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,2]]},"references-count":47,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,2]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2025.51878","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,2]]}}}