Hormonal Contraceptives and Migraine: Is It Time to Revisit Stroke Risk?

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Current oral contraceptive products contain lower doses of estrogen than those used in the past, prompting reconsideration of risks and benefits.
Current oral contraceptive products contain lower doses of estrogen than those used in the past, prompting reconsideration of risks and benefits.

Migraine with aura affects an estimated one-third of migraineurs1 and has been linked to an elevated stroke risk, especially among young women. A study published in 2016 in Neurology found a significant association between migraine with visual aura and ischemic stroke compared with controls without headache (hazard ratio [HR] 1.7; 95% CI, 1.2-2.6, P =.008), particularly cardioembolic stroke (HR 3.7; 95% CI, 1.6-8.7, P =.003).2

The use of combined hormonal contraceptives (CHC) is another factor that is independently associated with increased risk of stroke, and CHC use has been found to further increase the stroke risk associated with migraine – one recent review found a 2-fold to 4-fold risk of stroke among migraineurs using CHCs vs those not using CHCs.3

In light of such findings, current guidelines advise against the prescription of CHCs for women who experience migraine with aura.4 However, some experts have suggested that this recommendation is outdated. In a review published in 2017 in the Cleveland Clinic Journal of Medicine, Calhoun and Batur stated that “this contraindication is based on data from the 1960s and 1970s, when oral contraceptives contained much higher doses of estrogen. Stroke risk is not significantly increased with today's preparations, many of which contain less than 30 μg of ethinyl estradiol.”5

They point to results of a 5-year Danish case-control study published in 2002 that showed the stroke risk associated with CHCs to be directly correlated with estrogen dose.6 No increased risk was observed with a formulation containing 20 µg, while the 50-µg formulation was linked with a 4.5 odds ratio. In addition, a large US study published in 1998 observed no increase in stroke risk among women using low-dose CHCs.7 Calhoun and Batur added that continuous use of ultra-low-dose formulations (containing ≤20 μg of ethinyl estradiol) may reduce aura frequency and prevent menstrual migraine.

They concluded that if pregnancy prevention is the only goal for a patient with migraine with aura, they would recommend a contraceptive without estrogen. “However, we would consider prescribing a combined hormonal contraceptive in a low-dose regimen if the patient prefers this regimen for other health benefits (eg, acne control), if she has no other risk factors for stroke, and if she gives her informed consent after a discussion of the risks and benefits,” they wrote. 

For additional perspectives, Neurology Advisor consulted Nauman Tariq, MD, assistant professor of neurology and director of the Headache Center at Johns Hopkins Hospital, and Andrew Charles, MD, professor of neurology at the David Geffen School of Medicine at UCLA and director of the UCLA Goldberg Migraine Program.

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