Higher Stroke Risk Associated With Estrogen Contraceptives in Women With Migraine

Women with migraine with aura are at an increased risk for stroke if they are taking high-dose estrogen-containing contraceptives, according to findings from a systematic review published in Headache.

Researchers conducted a review of randomized controlled trials and observational studies assessing female patients with migraine with aura taking combined hormonal contraceptives (CHCs) at varying doses. In addition, all studies reported ischemic or hemorrhagic stroke outcomes in these patients.

A total of 15 studies were included in the final analysis. Of women with migraine who used CHCs with estrogen of any dose, point estimates for odds ratios (ORs) for ischemic stroke ranged from 2.08 to 16.9. In the 7 included studies that assessed an interaction effect between CHC use and migraine, the researchers found no such effect.

There was an increased risk for stroke among women with migraines who used CHCs in 2 studies (OR 2.1 [95% CI, 1.0-4.6] and 2.15 [95% CI, 0.85-5.45]). According to findings from 1 study, there was an increased risk for stroke among patients with migraine with aura vs those without migraine aura (OR 6.1; [95% CI, 3.1-12.1] vs 1.8 [95% CI, 1.1-2.9], respectively).

Women with migraine with aura who smoked and used CHCs also had a 7.0-fold greater chance of stroke (95% CI, 1.4-73.7) vs similar patients who did not smoke.

The observational studies included in this systematic review all held low GRADE levels of evidence, limiting the overall findings. In addition, some of the reported ORs were based on studies featuring small patient numbers. Some of the studies did not describe the doses of contraceptives used by participants. Also, a few articles in this review used self-reports instead of medical assessment for identifying migraine.

Because the review also found that women taking ≥50 µg ethinyl estradiol had a greater risk for stroke compared with those taking ≤35 µg ethinyl estradiol, the investigators indicate, “it seems reasonable to recommend that the lowest possible dose of estrogen be used if a CHC is prescribed to a woman with migraine.”

The review article’s authors further suggest that individualized assessments of risks and benefits of prescribing oral contraceptives should be discussed with patients, as the absolute risk for stroke was “low even in the presence of these risk factors,” and there may be patients who may benefit from the medication.

Reference

Sheikh HU, Pavlovic J, Loder E, Burch R. Risk of stroke associated with use of estrogen containing contraceptives in women with migraine: a systematic review [published online November 15, 2017]. Headache. doi:10.1111/head.13229