Hormonal Contraceptive Use, Stress Disorders, and Cardiovascular and Thrombotic Risk in Women.

Importance: Stress and its psychiatric consequences-including depression, anxiety, and posttraumatic stress disorder (PTSD)-are pertinent to women's cardiovascular health, but research on intersections with relevant sex-specific factors (eg, hormonal contraceptives) is lacking. Objective: To examine whether stress-related psychiatric diagnoses moderate associations between hormonal contraceptive use and cardiovascular and thrombotic risk. Design, Setting, and Participants: 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. Exposures: 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 International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes and analyzed as separate diagnoses, and lifetime history of combined hormonal contraceptive use, defined by RxNorm codes. Main Outcomes and Measures: The primary outcomes were major adverse cardiovascular events (MACE; defined as ICD-10 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. Results: In this sample of 31 824 women (mean [SD] age, 38.5 [10.6] years), over one-third (11 950 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). Conclusions and Relevance: 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.