New research presented at the European Stroke Organisation Conference (ESOC) 2025 in Helsinki, Finland, found that combined oral contraceptives are associated with a threefold increased risk of cryptogenic ischemic stroke in young women, independent of other established risk factors.
Researchers for the Searching for Explanations for Cryptogenic Stroke in the Young (SECRETO) study analyzed data from 268 women aged 18 to 49 years with cryptogenic ischemic stroke and 268 age-matched stroke-free controls across 14 European centers. Among participants, 66 patients and 38 controls were using combined oral contraceptives (OCs) at the time of assessment.
After adjusting for age and established comorbidities, including hypertension, smoking, migraine with aura, and abdominal obesity, OC use was associated with an adjusted odds ratio of 3 (95% confidence interval [CI] = 1.61-5.57). Notably, researchers found no significant interactions between OC use and these risk factors.
"Our findings confirm earlier evidence linking oral contraceptives to stroke risk," said Mine Sezgin, MD, Department of Neurology, Istanbul University, and lead author of the study, in a press release. "What's particularly notable is that the association remains strong even when accounting for other known risk factors, which suggests there may be additional mechanisms involved—possibly genetic or biological."
Cryptogenic ischemic stroke, defined as stroke with no identifiable cause, accounts for up to 40% of all ischemic strokes in young adults. Despite this prevalence, the contribution of sex-specific risk factors, such as contraceptive use, has remained underexplored. SECRETO is among the few studies to focus specifically on cryptogenic stroke in young women.
Most OC users in the study were taking ethinylestradiol-based formulations, for which the median dose was 20 micrograms. Other documented estrogen types included estradiol hemihydrate and estradiol valerate.
The researchers standardized their analysis by calculating equivalent estrogen doses for each patient. "While our data provides important initial insights, larger studies are needed to determine if certain formulations carry different levels of risk. This knowledge could help guide more personalised contraceptive choices for women," Dr. Sezgin explained.
"Our findings should prompt more careful evaluation of stroke risk in young women, particularly those with additional risk factors," concluded Dr. Sezgin.
The researchers plan to explore biological and genetic mechanisms underlying the observed association between combined OC use and increased stroke risk to better understand how hormonal contraceptives may independently elevate stroke risk.
Source: Conference Press Release
