In a groundbreaking study poised to reshape our understanding of women’s cardiovascular health, investigators from Mass General Brigham have unveiled novel insights into how hormonal contraceptive use intersects with stress-related psychiatric disorders to influence cardiovascular and thrombotic risk. Led by Antonia Seligowski, PhD, from the Neurocardiac Effects of Stress & Trauma Laboratory within the Department of Psychiatry, this research confronts a critical gap in medical knowledge by exploring the nuanced interplay between mental health, hormone use, and cardiovascular outcomes in women.
Cardiovascular disease (CVD) remains the leading cause of mortality among women in the United States, claiming the lives of over 400,000 women annually. This stark reality underscores the urgent imperative to delineate risk factors that disproportionately impact women. Among these risk factors, chronic stress and stress-related psychiatric conditions such as anxiety, depression, and post-traumatic stress disorder (PTSD) have drawn increasing attention for their profound effects on cardiovascular health. Women experience these disorders at higher rates compared to men, yet the mechanisms linking mental health and cardiovascular risk in women remain incompletely understood.
The widespread use of hormonal contraceptives—by approximately 9.1 million women in the U.S.—adds another layer of complexity. These contraceptives function by modulating endogenous hormone levels, suppressing natural estradiol and progesterone production, but their broader systemic effects, particularly in the context of psychological stress, have remained underexplored. Historically, research on hormonal contraception has largely excluded women with significant psychiatric comorbidities, focusing instead on young, generally healthy populations, thus limiting clinical guidance for women managing both hormone use and mental health challenges.
Bridging this critical knowledge gap, Dr. Jordan Thomas and colleagues undertook an expansive analysis utilizing healthcare records from 31,824 women enrolled in the Mass General Brigham Biobank, a rich repository of longitudinal health data. By cross-referencing diagnostic codes for stress-related disorders, major adverse cardiovascular events (MACE), deep-vein thrombosis, and prescriptions for hormonal contraceptives, the team delineated patterns of cardiovascular risk stratified by mental health status and hormone use.
Their findings reveal a striking dichotomy: in women with anxiety or depression, hormonal contraceptive use was correlated with a reduced risk of major adverse cardiovascular events. This counterintuitive protective association contrasts with the prevailing assumption that hormonal manipulation might exacerbate cardiovascular risk. However, this protective effect was absent in women diagnosed with PTSD, suggesting a potentially differential pathophysiological response linked to this severe stress disorder. These preliminary results raise provocative questions about the mechanisms by which psychological stress modulates hormonal effects on cardiovascular function.
The absence of a protective effect in women with PTSD implicates complex neuroendocrine and immunological pathways, given PTSD’s association with heightened sympathetic nervous system activity, chronic inflammation, and endothelial dysfunction—all contributory factors to cardiovascular pathology. Hormonal contraceptives, by altering estrogen and progesterone levels, may interact with these stress-induced physiological disturbances, modulating cardiovascular risk in ways that warrant further clarification.
Implications for clinical practice are profound. The findings suggest that assessment of psychiatric history, particularly PTSD, could become integral to contraceptive counseling and cardiovascular risk stratification in women. If substantiated through future research, this evidence could guide personalized medicine approaches, optimizing contraceptive choice in the context of mental health to mitigate avoidable cardiovascular events.
Looking forward, Dr. Seligowski’s team envisions a clinical study designed to collect prospective physiological data on the impact of specific hormonal contraceptive formulations on cardiovascular risk markers, including blood pressure regulation, vascular endothelial function, and biomarkers of coagulation—a key determinant of thrombotic risk. This longitudinal study aims to dissect how these parameters differ among women with and without stress-related psychiatric disorders, with participants undergoing annual follow-ups to monitor emergent clinical events such as thrombotic episodes.
Such research endeavors have the potential to unravel the biological substrates driving the observed epidemiological trends and to translate these insights into actionable clinical strategies. By integrating psychiatric evaluation with cardiovascular risk assessment and hormonal management, healthcare providers may in the future avert a significant fraction of female cardiovascular morbidity and mortality currently unaddressed by conventional paradigms.
This pioneering investigation represents a pivotal advancement in the domain of sex-specific medicine, emphasizing the imperative to consider psychological stressors as modulators of cardiovascular risk, particularly in the context of pharmaceutical hormone exposure. As the field moves towards precision medicine, understanding the interdependence of mental health and endocrine influences on cardiac outcomes will be critical to enhancing healthspan and quality of life for women.
Authorship of this study included key contributors from Mass General Brigham—Robyn Ellis, Shady Abohashem, Anahita Dua, Emily Lau, Karen Miller, Rachel Rosovsky, Ahmed Tawakol, and Michael Osborne—reflecting a multidisciplinary collaboration harnessing expertise across psychiatry, cardiovascular medicine, and epidemiology. Disclosure statements note industry relationships for some authors, emphasizing transparency in potential conflicts of interest.
Published in the prestigious journal JAMA Network Open, this research stands as a significant call to action for both the scientific community and clinicians alike. Its findings illuminate the intricate connections between psychiatric health, hormonal regulation, and cardiovascular disease, charting a promising course for future inquiry and intervention strategies aimed at reducing the disproportionate burden of cardiovascular disease among women.
Subject of Research: The investigation focused on the intersection of hormonal contraceptive use, stress-related psychiatric disorders, and their combined influence on cardiovascular and thrombotic risk in women.
Article Title: Hormonal contraceptive use, stress disorders, and cardiovascular and thrombotic risk in women
News Publication Date: 2-Jan-2026
Web References:
DOI link: http://dx.doi.org/10.1001/jamanetworkopen.2025.51878
Keywords: Clinical medicine, cardiovascular disease, hormonal contraception, stress disorders, PTSD, anxiety, depression, thrombosis, women’s health, neurocardiology, precision medicine
