Estrogen Exposure from Modern Hormonal Contraceptives and Vascular Risk in Women with Migraine: A Nationwide Electronic Health Record Database Study
Keiko Ihara1, William Pike2, Gavin Hui2, Saurabh Gombar2, Alison Callahan2, Michael L. Jackson2, Gretchen Tietjen3, Chia-Chun Chiang4
1Keio University School of Medicine, 2Atropos Health, 3University of Toledo, 4Mayo Clinic
Objective:
To assess vascular risk associated with estrogen-containing combined hormonal contraceptives (CHCs) in migraine by leveraging a nationwide electronic health record (EHR) database
Background:
Several guidelines list migraine with aura (MwA) as a contraindication to CHC use due to increased vascular risks. However, modern CHCs contain substantially lower dosages of estrogen than when first introduced in 1960. The vascular risk associated with modern CHCs in patients with migraine is understudied.
Design/Methods:
Using a US-nationwide de-identified EHR database, we included female patients aged 18-45 with a migraine diagnosis who had ≥3 office visits within 3 years and were prescribed ≥1 migraine-specific medication within 6 months following the first outpatient visit. Data after 2010 was used, excluding patients with prior cardiovascular events. We compared the incidence of a composite endpoint, consisting of acute ischemic stroke, acute myocardial infarction, deep vein thrombosis/pulmonary embolism, and intravenous thrombolytic administration, between CHC users and non-users, and between MwA and MwoA subgroups in the overall migraine cohort and in each subgroup by high-dimensional propensity score matching.
Results:
We identified 5535 CHC users and 21520 non-users with migraine. 114 (2.06%) users and 547 (2.54%) non-users had ≥1 vascular event. For the overall migraine group, and separately in the MwA and MwoA subgroups, there was no significant difference in the composite endpoint between users and non-users. Among users, MwA and MwoA did not significantly differ in the outcomes. For non-users, MwA was associated with a higher incidence of acute ischemic stroke (HR 2.45; 95%CI, 1.58–3.78; p<0.001) and composite endpoint (HR 1.34; 95%CI, 1.08–1.67); p=0.008), compared to MwoA.
Conclusions:
Our real-world, large data analysis showed that in young female migraine patients, estrogen exposure from CHCs was not associated with vascular risks, suggesting the need for re-evaluation of current guidelines. We also confirmed that aura increased vascular risk in patients with migraine not using CHCs.
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