Exogenous estrogen exposures and stroke risk in migraine with aura
Embargo Date
2027-05-13
OA Version
Citation
Abstract
Combined oral contraceptives are contraindicated in persons with migraine with aura due to stroke risk. Similarly, some guidelines for hormone therapies used for treatment of menopausal symptoms recommend caution in persons with migraine with aura. However, this guidance is informed by sparse or older evidence reflective of higher doses than typically prescribed today. This dissertation aims to, among female individuals with migraine with aura, describe the utilization of estrogen-containing oral contraceptives and hormone therapy for menopause and to evaluate the impact of use of these medications with respect to risk of stroke. The first study describes the utilization of oral contraceptives, including those with and without estrogen, as well as hormone therapy for menopause among individuals with migraine with aura at relevant age ranges corresponding with typical use. This study evaluates use before and after diagnosis with migraine with aura, overall and over calendar time. The second study compares the risk of ischemic and any stroke among individuals of reproductive age initiating use of combined oral contraceptives and progestogen-only pills. The third study evaluates the risk of ischemic, hemorrhagic, and any stroke among individuals with migraine with aura of plausible menopausal age initiating hormone therapy for menopause compared with non-users. Both comparative studies use inverse probability of treatment and censoring weighting to account for confounding and differential censoring and estimate absolute and relative risks to help contextualize findings for public health decision making. All three studies are conducted using the Clinical Practice Research Datalink (CPRD) Aurum, longitudinal primary care medical record data from the United Kingdom. Linked hospital data, available for most individuals, are also leveraged for outcome assessment in the comparative studies. This dissertation found that, despite contraindications, utilization of combined oral contraceptives decreased but did not fully cease after diagnosis with migraine with aura, with 15% of individuals of reproductive age prescribed combined oral contraceptives post-diagnosis. Initiation and continued use of combined oral contraceptives was associated with approximately one additional ischemic stroke per 10,000 people in the first year of use compared with progestogen-only pills. Utilization of hormone therapy for menopause was common among individuals of post-reproductive age with diagnosed migraine with aura, with nearly half having a prescription. Initiation and continued use of hormone therapy was associated with approximately 10 fewer ischemic strokes per 10,000 people in the first year of use compared with non-use, with this reduction predominantly driven by use of transdermal and vaginal formulations. While some findings were imprecisely measured, this work provides reassurance that the risk of stroke associated with these estrogen-containing medications is not greatly increased among individuals with migraine with aura relative to historical estimates in more general populations.
Description
2026