Use of combined hormonal contraception and stroke: A case-control study of the impact of migraine type and estrogen dose on ischemic stroke risk.

Abstract

To clarify how factors such as estrogen dose and migraine history (including migraine subtype) impact ischemic stroke risks associated with combined hormonal contraceptive (CHC) use. CHC use in those with migraine with aura has been restricted due to concerns about stroke risk. We conducted a case-control analysis of stroke risk associated with estrogen dose and migraine history among CHC users in a large tertiary care center. All women aged 18-55 who used a CHC between January 1, 2010, and December 31, 2019, were identified. Those with a stroke diagnosis were identified using ICD codes and confirmed via chart and imaging review. Details of personal and family medical history, stroke evaluation, ethinyl estradiol dosing (EE; ≥30 vs. <30 μg), and demographics were collected. From a random sample of 20,000 CHC users without stroke, a control cohort (n=635) was identified and matched based on patient characteristics, medical and family histories, as well as stroke risk factors, to assess association between migraine diagnosis, migraine subtype, estrogen dose, and stroke. Of the 203,853 CHC users in our cohort, 127 had confirmed stroke (0.06%; CI 0.05%, 0.07%). In unadjusted analyses, a higher number of patients in the case cohort had a diagnosis of migraine (34/127, 26.8%) compared to controls (109/635, 17.2%; p=0.011). 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). Compared to no migraine, personal history of migraine increased the odds of stroke (OR, 2.00; CI 1.27, 3.17; p=0.003). 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). Overall stroke risk in our cohort of CHC users was low. When CHCs are used in those with migraine, formulations containing ≤30 μg EE are preferred. Shared decision-making should include discussions about ischemic stroke risks in patients with migraine, even those without aura.