Combined Oral Contraceptive Use May Triple the Risk of Cryptogenic Stroke in Young Women

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New research suggests that young women who use combined oral contraceptives may have a higher risk of cryptogenic ischemic stroke (CIS) than age-matched stroke-free controls.1

According to findings from the Searching for Explanations for Cryptogenic Stroke in the Young (SECRETO) study presented at the European Stroke Organization Conference (ESOC) 2025, the use of combined OCs was associated with a threefold increase in the risk of CIS among women aged 18 to 49 years.1

“[CIS] encompasses up to 40% of ischemic strokes in young adults despite comprehensive diagnostic investigations,” lead author Mine Sezgin, MD, of the Department of Neurology at Istanbul University, and colleagues wrote. “The role of sex-specific risk factors, such as [OC], and their interplay with other risk factors has not been thoroughly explored in young CIS.”1

Sezgin and colleagues conducted the prospective case-control and multicenter study of 268 women with CIS (median age, 39.8 years) and 268 age-matched stroke-free controls across 14 centers in Europe. Of the participants, 66 women with CIS and 38 controls received combined OCs, researchers noted.1

After adjusting for age and established comorbidities such as hypertension, smoking, migraine with aura, and abdominal obesity, investigators observed OC use remained associated with a significantly elevated stroke risk (adjusted odds ratio, 3.00, 95% CI 1.61–5.57). No significant interactions were found between OC use and these risk factors, suggesting that the increased stroke risk may operate independently of other known contributors.1

“Our findings confirm earlier evidence linking oral contraceptives to stroke risk,” Sezgin said 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.”2

Most study participants who used OCs (68%) were taking formulations containing ethinylestradiol, with a median dose of 20 µg. Other estrogen types included estradiol hemihydrate and estradiol valerate. Researchers calculated an equivalent estrogen dose across users to ensure consistency in analysis.1,2

“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,” Sezgin said in the press release.2

Sezgin emphasized the need for further investigation to determine whether risk differs by formulation and to explore potential underlying biological or genetic mechanisms. In the interim, clinicians are advised to carefully assess vascular risk when prescribing combined OCs, especially for women with known risk factors or a history of ischemic stroke. “Our findings should prompt more careful evaluation of stroke risk in young women, particularly those with additional risk factors,” Sezgin concluded.2

References:

1. Sezgin, M, Sarkanen T, von Sarnowski B, et al. Hormonal contraception increases the risk of cryptogenic stroke in young women (abstract O049). Presented at the European Stroke Organisation Conference; 21 May 2025; Vienna, Austria.

2. Combined oral contraceptives triple risk of cryptogenic stroke in young women, new study shows. News release. European Stroke Organization. May 20, 2025. Accessed May 23, 2025. https://www.eurekalert.org/news-releases/1084372