Oral contraceptives triple stroke risk in young women

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The risk of cryptogenic stroke in young women is increased 3-fold by the use of combined oral contraceptives (OCs), according to a recent study presented at the European Stroke Organization Conference 2025.¹

This data is supported by prior research about the impact of hormonal contraception on vascular risk in reproductive-aged women. However, this is one of the first studies to evaluate risk factors of cryptogenic stroke in this population.¹

Persistent risk

“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,” said Mine Sezgin, MD, lead study author from the Department of Neurology at Istanbul University.¹

Up to 40% of ischemic strokes in young adults are cryptogenic, which have no identifiable cause. Investigators evaluated combined OCs as a risk factor in the Searching for Explanations for Cryptogenic Stroke in the Young study.¹

Understanding cryptogenic stroke

Women aged 18 to 49 years with cryptogenic ischemic stroke (CIS) were included in the analysis, alongside age-matched stroke-free controls. Each group had 268 patients, with 66 and 38, respectively, reporting combined OC use. Adjustments were made for age and comorbidities such as smoking, hypertension, migraine with aura, and abdominal obesity.¹

Investigators determined the OC status in female stroke patients for comparisons with healthy controls.² Assessments were performed using multivariable conditional logistic regression models.

OC use independently associated with increased stroke risk

Patients were aged a median of 39.8 years, and CIS patients had increased diabetes, hypertension, smoking, abdominal obesity, and migraine with aura rates in the unadjusted analysis compared with controls. Combined OC was reported in 68 CIS patients and 38 controls, with ethinylestradiol use reported in 68% of the study population.²

A median dose of 20 μg was reported for ethinylestradiol and its equivalents in the CIS group. Odds ratios for CIS were 2.37, 2.37, 5.19, and 9.13 for smoking, abdominal obesity, migraine with aura, and age over 35 years, respectively.²

An adjusted odds ratio of 3 was reported for CIS risk in women with OC use. As OC use was not significantly linked to risk factors of CIS, this indicated an independent association with increased stroke risk. Investigators recommended additional research but warned clinicians to remain cautious when prescribing combined OCs to women with known vascular risk factors.¹

Clinical implications and supporting data

“Our findings should prompt more careful evaluation of stroke risk in young women, particularly those with additional risk factors,” said Sezgin.¹

This data is supported by a study published in The BMJ in the first quarter of 2025.³ Multiple forms of hormonal contraceptives were evaluated, with oestrogen products leading to the greatest risks in women aged 15 to 49 years. Contraception use was determined based on prescription fills.

The final analysis included 2,025,691 women with 22,209,697 person years of follow-up time. Among these patients, an adjusted incidence rate ratio of 2 was reported for ischemic stroke when using oral contraceptives with oestrogen and progestin. This highlighted hormonal contraceptives as a risk factor for ischemic stroke.³

References

1. Combined oral contraceptives triple risk of cryptogenic stroke in young women, new study shows. Beyond. May 20, 2025. Accessed May 29, 2025. https://www.eurekalert.org/news-releases/1084372.
2. Sezgin M, Sarkanen T, von Sarnowski B, et al. Hormonal contraception increases the risk of cryptogenic stroke in young women. Abstract. Presented at the European Stroke Organization Conference, May 21, 2025, Vienna, Austria.
3. Krewson C. Hormonal contraceptives linked to increased stroke and heart attack risk. Contemporary OB/GYN. February 13, 2025. Accessed May 29, 2025.