Women who have migraines with aura are at increased risk of stroke. Now, a new systematic review suggests that use of combined hormonal contraceptives by these patients raises their stroke risk over and above the already increased risk.
Women who have migraines with aura are at increased risk of stroke. Now, a new systematic review suggests that use of combined hormonal contraceptives (CHCs) by these women raises their stroke risk over and above the already increased risk. The association is less clear with newer formulations that use lower doses of estrogen.
“The association was clear for women using high estrogen dose (≥50 mg ethinyl estradiol) combined hormonal contraceptives. There is insufficient evidence to determine whether stroke risk is also increased with the use of low estrogen dose (<35 mg ethinyl estradiol) combined hormonal contraceptives in this population,” wrote first author Huma Sheikh, MD, of Mt Sinai-Icahn School of Medicine, New York, NY, and colleagues.
About 3 times as many women suffer from migraines as men. Women with migraine have roughly double the risk of ischemic stroke as women without migraine, and those who have migraine with aura are particularly at risk. Moreover, women are more likely to suffer from migraines during their reproductive years, precisely the time when they may be taking oral contraceptives.
Both WHO and ACOG guidelines warn about using CHCs in women with migraine with aura. The recommendations are based on past studies suggesting that CHCs may further increase the risk of stroke associated with migraine, and that the estrogen component may be responsible. However, most of this evidence comes from older studies in which CHCs contained higher estrogen content. Most currently used CHCs contain low-dose estrogen. That raises the question whether newer formulations are safer in women with migraines, and whether guidelines should be updated.
To investigate the issue, researchers searched 3 different databases for studies in English published from inception through January 2016. The review included 15 studies, of which 11 were case-control studies.
In general, the review showed that most studies were small and lacked good quality evidence. Overall, the risk of ischemic stroke was increased 2 to 17 times in women with migraine who used CHCs. But that was over a broad range of estrogen doses. Newer studies were more likely to show no clear association between CHCs and stroke risk, which may reflect the decreasing dose of estrogen over time, according to authors.
Studies were limited by poor reporting of estrogen type and dose. Just 1 study specifically analyzed stroke risk associated with estrogen dose. That study found increased likelihood of stroke with higher dose estrogen (>50 ug) in women with migraine. But the authors did not report the odds of stroke in women with migraines on CHCs containing higher dose estrogen. Likewise, only 6 studies distinguished between presence or absence of migraine with aura. And, only 1 study assessed risk of stroke based on migraine subtype. That study was the largest, with 1884 women who used CHCs within 90 days of stroke: increased risk in women with aura was increased 6-fold.
The authors stressed that, even though studies suggest increased risk of stroke with CHC use in women with migraine, the absolute risk is still relatively low. Evidence suggests that excess stroke risk from CHCs in women with migraine with aura is about 18 per 100,000 women per year. They also mentioned several benefits of CHCs, including avoidance of unintended pregnancy (pregnancy itself carries increased stroke risk), treatment for endometriosis, menstrual cramps, dysmenorrhea, menorrhagia (and associated anemia), acne, and hirsutism. Some evidence also suggests CHCs may improve menstrual migraine.
“Given all of these factors, it may be reasonable to base the decision regarding use of CHCs in women with migraine with aura on an individualized assessment of risks and benefits rather than continuing a strict prohibition on use. Other risk factors for stroke, such as age over 35, family history, and obesity, should be taken into account,” they concluded, emphasizing that the lowest possible dose of estrogen should be prescribed. Larger, better quality studies are needed to evaluate the effect of estrogen dose on stroke risk in women with migraine more fully.
-Systematic review found combined hormonal contraceptives (CHCs) increase the risk of stroke over and above the already increased stroke risk carried by women with migraine with aura
-Newer studies were more likely than older ones to show no clear association between CHCs and stroke risk, which may reflect the decreasing dose of estrogen in CHCs over time
-The decision to use CHCs in women with migraine with aura should be individualized, based on a thorough discussion of risks and benefits
-More research is needed to evaluate the effect of estrogen dose on stroke risk
1. Sheikh HU, Pavlovic J, Loder E, et al. Risk of stroke associated with use of estrogen containing contraceptives in women with migraine: a systematic review. Headache. 2018;58:5-21.
2. Chang C, Donaghy M, Poulter N. Migraine and stroke in young women: case-control study. BMJ. 1999;318:13-18.
3. Champaloux SW, Tepper NK, Monsour M, et al. Use of combined hormonal contraceptives among women with migraines and risk of ischemic stroke. Am J Obstet Gynecol. 2017;216:489.e1-489.e7.