Migraine without Aura May Increase Stroke Risk for Women Taking Combined Hormonal Contraceptives

In a large cohort of reproductive-age women using combined hormonal contraceptives, those with a history of migraine had a significantly increased risk for ischemic stroke compared with those without a history of migraine, according to new findings published in the journal Headache.

However, the investigators reported, the elevated risk of stroke was only sigificant among those who had migraine without aura compared with those without migraine, a finding in stark contrast with clinical guidelines that “discourage the use of combined hormonal contraceptives (CHC) in women who experience migraine with aura due to concerns about ischemic stroke,” Pelin Batur, MD, a professor of OB/GYN and reproductive biology at the OB/GYN & Women’s Health Institute at Cleveland Clinic, and colleagues wrote.

Guidance of this nature significantly limits women’s choices for CHC use, given that one-third of patients with migraine have accompanying aura, observe the authors. Importantly it may also lead to nonadherence with a contraceptive method if that method does not meet a woman’s needs or interests, and potentially to an unplanned pregnancy.

Batur et al also note that current information on how factors such as dose of estrogen and migraine history and subtype impact the risk of stroke associated with low-dose CHC “is not only based on limited observational data, but also has been contradictory."

“Thus, it is of utmost importance to know if there are ways to prescribe CHCs that may mitigate these risks,” they wrote.

The researchers conducted a case-control analysis to better understand whether migraine history compounds stroke risk in CHC users and whether stroke risk differed based on more commonly used doses of ethinyl estradiol (EE) dose (30–35 vs <30 μg EE). The study included 203 853 women cared for in a large urban academic tertiary care center, aged 18 to 55 years who had used CHCs between Jan. 1, 2010, to Dec. 31, 2019.

Overall, 127 women had confirmed cases of stroke while taking CHC at the time and were placed into the case cohort, while 635 women were placed into a control cohort. The investigators found that on average, women who had experienced a stroke while on CHC were overweight (mean BMI 29.4 kg/m2), White (84%), and had never smoked (70%). While obvious risk factors for stroke were not common, among those that were identified, the most common was hypertension (35%), followed by hyperlipidemia (16%), and diabetes (12%).

Batur and colleagues found that a higher proportion of patients in the case cohort had a diagnosis of migraine (26.8%) compared with those in the control cohort (17.3%). Also, among the case cohort, 11.0% reported migraine with aura vs 8.5% of controls; 15.7% of the case cohort reported migraine without aura versus 8.7% of controls.

Investigators reported that use of a CHC with an EE dose ≥of 30 g was more common among participants in the case cohort vs those in the control group (62.2% vs. 51.7%; p = 0.030).

Patients who received an EE dose ≥30 g had an increased risk for stroke compared with those prescribed <30 g EE (OR = 1.52; 95% CI, 1.02-2.26), according to the researchers.

Additionally, the odds of stroke among participants with a history of migraine were 2 times that of those with no history of migraine (OR, 2; 95% CI, 1.27-3.17).

However, when they compared participants with migraine with those with no migraine history, the researchers found that stroke risk was only significant in those with migraine without aura (OR = 2.35; 95% CI, 1.32-4.2), not among those with migraine with aura.

“Our findings highlight the importance of appropriate patient education on ischemic stroke risks and shared decision-making for all women who start a CHC with a history of migraine, even those without aura. This should include a shared decision-making process in which stroke risk associated with the use of CHCs is compared to stroke risks during pregnancy.

“Women with migraines who prefer to be on estrogen-containing contraceptives for pregnancy prevention or a medical need should consider options that have <30 μg EE, and possibly <20 μg, if medically appropriate, the authors concluded.

The authors point to several study limitations, including the retrospective design, use of electronic medical records to obtain data for CHC codes, length of the observation period which could allow for a variety of exposures as well as physiologic changes.

Reference: Batur P, Yao M, Bucklan J, et al. Use of combined hormonal contraception and stroke: A case-control study of the impact of migraine type and estrogen dose on ischemic stroke risk. Headache. Published online February 18, 2023. doi:10.1111/head.14473