Estrogen, migraine, and vascular risk

Migraine has a predilection for female sex and the course of symptoms is influenced by life stage (presence of menstrual cycle, pregnancy, puerperium, menopause) and use of hormone therapy, such as hormonal contraception and hormone replacement therapy. Hormonal changes figure among common migraine triggers, especially sudden estrogen drop. Moreover, estrogens can modulate neuronal excitability, through serotonin, norepinephrine, dopamine, and endorphin regulation, and they interact with the vascular endothelium of the brain. The risk of vascular disease, and ischemic stroke in particular, is increased in women with migraine with aura (MA), but the link is unclear. One hypothesis posits for a causal association: migraine may cause clinical or subclinical brain lesions following repeated episodes of cortical spreading depression (CSD) and a second hypothesis that may explain the association between migraine and vascular diseases is the presence of common risk factors and comorbidities. Estrogens can play a differential role depending on their action on healthy or damaged endothelium, their endogenous or exogenous origin, and the duration of their treatment. Moreover, platelet activity is increased in migraineurs women, and it is further stimulated by estrogens.This review article describes the course of migraine during various life stages, with a special focus on its hormonal pathogenesis and the associated risk of vascular diseases.