In a compelling advancement within stroke research, a new study unveiled at the European Stroke Organisation Conference (ESOC) 2025 has linked the use of combined oral contraceptives (OCs) to a substantially increased risk of cryptogenic ischemic stroke (CIS) in young women. This revelation underscores the critical need for deeper exploration into the vascular effects of hormonal contraception, particularly among women of reproductive age, a demographic for which stroke risk factors have been historically understudied and underreported.
Cryptogenic ischemic stroke—characterized by the absence of identifiable causes following extensive diagnostic evaluation—constitutes a perplexing and significant subset of ischemic strokes, especially in the younger population. Representing nearly 40% of ischemic stroke cases in young adults, CIS remains a diagnostic enigma, often leaving clinicians without a clear pathophysiological explanation or targeted preventive strategies. While traditional stroke risk factors—such as hypertension, smoking, migraine with aura, and obesity—have been extensively documented, the sex-specific contributors, and notably the influence of hormonal contraceptives, have received limited focused scrutiny until now.
The cornerstone of this new research is the SECRETO (Searching for Explanations for Cryptogenic Stroke in the Young) study, which methodically evaluated 268 young women aged 18 to 49 years with cryptogenic ischemic stroke alongside an equal number of age-matched controls devoid of stroke history. Conducted across 14 centers in Europe, this robust multi-center investigation provides compelling epidemiological evidence by comparing combined OC usage in affected individuals versus controls. Within the cohort, 66 stroke patients and 38 control participants reported active use of combined oral contraceptives, enabling a rigorous evaluation of stroke risk linked directly to hormonal contraceptive exposure.
Statistical analyses adjusted for confounding factors including age and established vascular risk variables yielded a striking finding: combined oral contraceptive use was associated with a threefold increase in the odds of cryptogenic ischemic stroke, reflected by an adjusted odds ratio of 3.00 with a 95% confidence interval ranging from 1.61 to 5.57. Importantly, no significant interactions emerged between OC use and other risk factors, suggesting that the elevated stroke risk operates independently, thereby implicating novel pathogenic pathways or mechanisms intrinsic to hormonal contraception itself.
Dr. Mine Sezgin, the study’s lead investigator and neurologist specializing in stroke research at Istanbul University, emphasized the significance of these findings. She highlighted that while previous literature has noted a general association between oral contraceptives and stroke, this investigative effort specifically isolates cryptogenic stroke—a subtype lacking direct etiological clarity—and demonstrates a robust association independent of classical risk factors. Dr. Sezgin posited the potential involvement of genetic predispositions or yet-uncharacterized biological pathways, thereby opening new avenues for mechanistic research into how hormonal contraceptives may contribute to cerebrovascular vulnerability.
Most participants utilizing combined oral contraceptives were prescribed formulations centered on ethinylestradiol, with a median estrogen dose measured at 20 micrograms. Additionally, the study cataloged a heterogeneous distribution of other estrogen types—namely estradiol hemihydrate and estradiol valerate—illuminating the pharmacological diversity among contraceptive agents. To standardize comparisons, researchers calculated equivalent estrogen doses, allowing finer resolution in assessing dose-dependent risk dynamics across different hormonal formulations, although definitive conclusions on formulation-specific risks remain pending further investigation.
Dr. Sezgin underscored the clinical implications of the findings, advocating for heightened vigilance when prescribing combined OCs to women who present additional vascular risk factors or harbor a historical predisposition toward ischemic stroke. She stressed that while hormonal contraception remains a cornerstone of reproductive healthcare, this emerging evidence necessitates personalized risk assessment frameworks to balance contraceptive benefits against cerebrovascular risk, particularly in young women whose stroke risk had previously been underappreciated.
The study also raises critical questions regarding the underlying biological mechanisms that confer risk independently of comorbidities such as hypertension or smoking. Potential mechanisms might include prothrombotic effects induced by estrogenic compounds, alterations in coagulation cascades, endothelial dysfunction, or complex interactions with genetic polymorphisms affecting vascular integrity and hemostasis. Unraveling these pathways is essential to develop safer contraceptive methodologies and to better stratify patients based on individualized risk profiles.
As the researchers prepare for future prospective studies, they aim to dissect the genetic and molecular underpinnings contributing to the heightened stroke risk. Understanding whether specific genetic variants, such as those involved in coagulation factor regulation or vascular inflammation, interact with hormonal contraceptive use could revolutionize stroke prevention strategies tailored to women’s unique physiological and reproductive contexts.
The presentation of these data at ESOC 2025 carries significant implications for both clinical practice and public health policy. It urges clinicians, neurologists, and gynecologists alike to integrate vascular risk assessments into contraceptive counseling and to re-examine guidelines surrounding hormonal contraception prescriptions, particularly for women in demographics traditionally considered low-risk but who may harbor unrecognized vulnerabilities to cryptogenic ischemic stroke.
Moreover, this pivotal study galvanizes the broader scientific community to prioritize sex-specific research in stroke and cardiovascular disease more broadly. Given that stroke remains a leading cause of morbidity and mortality worldwide, delving into underexplored domains such as hormonal influences in young women represents an essential frontier for reducing global stroke burden.
In summary, the SECRETO study’s findings articulate a compelling narrative: combined oral contraceptives significantly elevate the risk of cryptogenic ischemic stroke in young women independent of other vascular risk factors. These data not only reinforce the need for cautious prescribing but also beckon a paradigm shift in how we understand, research, and ultimately mitigate stroke risk within the female population. As research accelerates in this domain, personalized medicine approaches tailored to women’s unique biological contexts may become integral in safeguarding cardiovascular health.
Subject of Research: The association between combined oral contraceptive use and the risk of cryptogenic ischemic stroke in young women.
Article Title: Combined Oral Contraceptives and Cryptogenic Ischemic Stroke Risk in Young Women: Insights from the SECRETO Study Presented at ESOC 2025
News Publication Date: 21 May 2025
References:
- Sezgin, M., et al. Hormonal contraception increases the risk of cryptogenic stroke in young women. Abstract O049, European Stroke Organisation Conference; 21 May 2025; Vienna, Austria.
- Yaghi, S., & Elkind, M. S. (2014). Cryptogenic stroke: A diagnostic challenge. Neurology. Clinical Practice, 4(5), 386–393.
Keywords: Hormonal contraception, oral contraceptives, cryptogenic ischemic stroke, stroke risk, young women, vascular risk factors, ethinyloestradiol, cerebrovascular disease, sex-specific risk, stroke prevention, neurology, SECRETO study.
