From the Guidelines
Oral contraceptive pills (OCPs) increase stroke risk primarily through their estrogen component, which promotes blood clot formation, with a direct, linear relationship between a higher dose of estrogen in combined hormonal contraception (CHC) and an increased risk of stroke, as reported in the 2024 guideline for the primary prevention of stroke 1. The estrogen in OCPs increases production of clotting factors and fibrinogen while decreasing natural anticoagulants, creating a hypercoagulable state. This can lead to thrombus formation that may travel to cerebral vessels and cause ischemic stroke. Key factors influencing stroke risk include:
- Dose of estrogen: Higher estrogen formulations (>50 mcg) carry greater risk than modern low-dose pills (20-35 mcg ethinyl estradiol) 1.
- Duration of use: Stroke risk increases after 1 year of use, with each additional 5 years of use further elevating the risk 1.
- Presence of other stroke risk factors: Women with additional risk factors such as smoking, hypertension, migraine with aura, diabetes, or thrombophilia are at higher risk 1. The use of progestin-only pills ("mini-pills") does not significantly increase stroke risk and are safer alternatives for women with stroke risk factors, as supported by the findings of a 2020 umbrella review on the association between reproductive health and cardiovascular disease 1. In clinical practice, it is essential to consider these factors when prescribing OCPs to minimize stroke risk, particularly in women over 35 who smoke or have multiple cardiovascular risk factors, and to consider non-hormonal contraception methods or progestin-only options as alternatives.
From the Research
OCP Mechanism of Stroke
The use of Oral Contraceptive Pills (OCPs) has been associated with an increased risk of stroke, particularly ischemic stroke. The mechanism by which OCPs increase the risk of stroke is not fully understood, but several factors are thought to contribute:
- Estrogen dose: High doses of estrogen (>50μg) are associated with a higher risk of stroke, while low doses (<50μg) may carry a lower or no increased risk 2, 3, 4.
- Progestin type: All four generations of progestin have been associated with an elevated risk of ischemic stroke, although the risk may be slightly lower with fourth-generation progestins 2.
- Presence of other risk factors: The risk of stroke is greatly increased if other risk factors are present, such as hypertension, cigarette smoking, and migraine 3, 4, 5.
Types of Stroke
OCPs have been associated with an increased risk of both ischemic and hemorrhagic stroke:
- Ischemic stroke: The risk of ischemic stroke is increased with OCP use, particularly with high doses of estrogen and in the presence of other risk factors 2, 3, 4.
- Hemorrhagic stroke: The risk of hemorrhagic stroke is also increased with OCP use, although the association is less clear-cut than for ischemic stroke 3, 5.
Study Findings
Several studies have investigated the association between OCP use and stroke risk:
- A meta-analysis of observational studies found that current use of OCPs was associated with a significantly increased risk of first-ever ischemic stroke, with a pooled odds ratio of 2.47 2.
- A case-control study found that current use of combined OCPs was associated with a slightly increased risk of hemorrhagic stroke, although the increase was only significant in developing countries 3.
- A review of epidemiological studies found that high estrogen content (>50μg) increased the risk of stroke, while low estrogen content (<50μg) carried a very low or no risk of stroke 4.
- A pooled analysis of two US studies found that current use of low-dose OCPs was not associated with an increased risk of stroke, although the risk may be elevated in certain subgroups, such as women with a history of migraine 5.