Headache. 2026 Apr 3. doi: 10.1111/head.70071. Online ahead of print.
ABSTRACT
BACKGROUND: Migraine is a neurologic disorder that disproportionately affects women and undergoes important changes across the menopausal transition. Estrogen fluctuations contribute to migraine expression and underlie the 3:1 female-to-male prevalence. Perimenopause, marked by hormonal variability and rising cardiometabolic risk, presents unique diagnostic and therapeutic challenges. Despite its high prevalence, evidence specific to perimenopausal and postmenopausal women remains limited.
OBJECTIVE: This review synthesizes current evidence on the epidemiology, pathophysiology, and management of migraine across the menopausal transition, with attention to hormone therapy, comorbidities, and emerging treatments.
METHODS: We conducted a narrative review of clinical and translational studies published within the past 5 years, supplemented by seminal mechanistic, epidemiologic, and guideline-defining studies published earlier. Relevant guideline statements from neurology, gynecology, and cardiovascular societies were also incorporated.
RESULTS: Unstable estradiol and progesterone levels during perimenopause can worsen migraine frequency and predictability. Migraine without aura often improves after menopause, whereas migraine with aura tends to persist and independently increases the risk of ischemic stroke and other vascular events. Midlife comorbidities-including vasomotor symptoms, sleep disturbance, mood disorders, and metabolic disease-further complicate management. Menopausal hormone therapy has variable effects. Oral estrogen, particularly at higher doses, may worsen migraine and elevate vascular risk, especially in women with aura. In contrast, low-dose transdermal estrogen-recommended by the North American Menopause Society-appears safer and better tolerated. Continuous progestogen regimens may reduce withdrawal-related attacks compared with cyclic regimens. Nonhormonal options, particularly selective norepinephrine reuptake inhibitors, may be considered when vasomotor symptoms coexist, whereas migraine-specific prevention should follow established evidence-based therapies. Traditional migraine therapies (triptans, NSAIDs, beta-blockers, topiramate, antidepressants) remain central but require tailoring to vascular, bone, and metabolic health. Newer agents-including calcitonin gene-related peptide monoclonal antibodies, gepants, and ditans-offer effective, non-vasoconstrictive alternatives, especially for women with cardiovascular contraindications.
CONCLUSIONS: Migraine during the menopausal transition reflects the interplay between hormonal dynamics and systemic health. Management requires balancing efficacy with vascular and metabolic safety while incorporating patient preferences. Evidence gaps include the lack of trials stratified by menopausal stage or migraine subtype. Multidisciplinary, menopause-informed care and prospective studies are needed to optimize outcomes in this population.
PMID:41934093 | DOI:10.1111/head.70071