What are the risks of cerebrovascular accident (CVA) or stroke associated with the use of various oral contraceptive pills (OCPs)?

From the Guidelines

Hormonal contraceptive pills with lower doses of ethinyl estradiol are recommended to minimize potential increased stroke risk, as stated in the 2024 guideline for the primary prevention of stroke by the American Heart Association/American Stroke Association 1. The risk of stroke associated with hormonal contraception varies depending on the type and formulation of the contraceptive method. Combined oral contraceptives (COCs) containing both estrogen and progestin pose a higher stroke risk than progestin-only pills, with lower-dose estrogen pills (containing 20-35 mcg ethinyl estradiol) being safer than higher-dose formulations 1. Some key points to consider when evaluating the risk of stroke with hormonal contraception include:

• The dose of estrogen in the contraceptive method, with lower doses associated with reduced risk 1
• The type of progestin used in the contraceptive method, with some progestins potentially affecting lipid profiles and glucose metabolism 1
• The presence of additional risk factors, such as smoking, hypertension, migraines with aura, age over 35, or previous cardiovascular issues, which may increase the risk of stroke with hormonal contraception 1
• The effectiveness of the contraceptive method, with some methods being more effective than others in preventing pregnancy 1 In terms of specific contraceptive methods, the following options are associated with varying levels of stroke risk:
• Progestin-only pills: no increased risk of stroke 1
• Progestin IUD: no increased risk of stroke 1
• Progestin implantation: no increased risk of stroke 1
• Combined oral contraception with ≤20 µg ethinyl estradiol: mild increase in stroke risk 1
• Combined oral contraception with 30-40 µg ethinyl estradiol: moderate to severe increase in stroke risk 1 For women with multiple risk factors, non-hormonal methods like copper IUDs or barrier methods offer effective contraception without stroke risks, and regular blood pressure monitoring is recommended for all women using hormonal contraception 1.

From the FDA Drug Label

Oral contraceptives have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes), although, in general, the risk is greatest among older (>35 years), hypertensive women who also smoke Hypertension was found to be a risk factor for both users and non-users, for both types of strokes, while smoking interacted to increase the risk for hemorrhagic strokes In a large study, the relative risk of thrombotic strokes has been shown to range from 3 for normotensive users to 14 for users with severe hypertension The relative risk of hemorrhagic stroke is reported to be 1. 2 for non-smokers who used oral contraceptives, 2.6 for smokers who did not use oral contraceptives, 7.6 for smokers who used oral contraceptives, 1.8 for normotensive users and 25. 7 for users with severe hypertension

The risk of stroke amongst various contraceptive pills is increased, particularly in older women (>35 years) who are hypertensive and smoke. The relative risk of thrombotic strokes ranges from 3 to 14, and the relative risk of hemorrhagic stroke is reported to be 1.2 to 25.7, depending on the presence of hypertension and smoking. Key factors that increase the risk of stroke include:

• Age: Women over 35 years
• Hypertension: Presence of high blood pressure
• Smoking: Interaction with smoking to increase the risk of hemorrhagic strokes It is essential to consider these risk factors when prescribing contraceptive pills, and to use the lowest possible dose formulation that is effective 2 2.

From the Research

Stroke Risks Amongst Various Contraceptive Pills

• The use of combined hormonal contraception (CHC) has been associated with an increased risk of ischemic stroke, particularly in women with migraine 3, 4, 5, 6.
• A case-control study found that CHC use in women with migraine with aura has been restricted due to concerns about stroke risk, and that formulations containing ≤30 μg ethinyl estradiol (EE) are preferred when CHCs are used in those with migraine 3.
• The study also found that stroke risk was higher with ≥30-μg EE doses compared to those using a <30-μg dose (OR, 1.52; CI 1.02,2.26; p = 0.040) 3.
• Another study found that limited evidence suggests a two- to fourfold increased risk of stroke among women with migraine who use combined oral contraceptives (COCs) compared with nonuse 4.
• A consensus statement from the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESC) suggests that combined hormonal contraceptive may further increase the risk of ischemic stroke in those who have migraine, specifically migraine with aura 5.
• A systematic review found that strong data on the joint effect of migraine and CHC use on risk of ischemic stroke are lacking, especially referring to the role of aura and headache frequency 6.

Migraine and Contraceptive Use

• Migraine is common among women of reproductive age and is associated with an increased risk of ischemic stroke 4, 5, 6.
• The use of hormonal contraception among women with migraine might further elevate the risk of stroke among women of reproductive age 4, 5.
• A study found that compared to no migraine, personal history of migraine increased the odds of stroke (OR, 2.00; CI 1.27,3.17; p = 0.003), and that compared to no migraine, stroke risk was not significantly increased in those with migraine with aura, but migraine without aura increased the risk (OR, 2.35; CI 1.32,4.2; p = 0.004) 3.

Hormonal Contraceptives and Stroke Risk

• Combined hormonal contraception (CHC) are short-acting, reversible methods containing both estrogen and progestin, and are associated with an increased risk of ischemic stroke 3, 7, 4, 5, 6.
• The general principles of CHC, including mechanism of action and effectiveness, are reviewed in a study, which also discusses clinical studies and specific considerations related only to pills, patches, or rings 7.
• A systematic review found that all the four included case-control studies reported increased odds of ischemic stroke in women with migraine and low-dose CHC use compared with those without migraine not using CHCs 6.