Migraine and menopause as converging factors in brain vulnerability: a hypothesis-driven perspective
Abstract
Migraine is a highly prevalent neurological disorder with a pronounced female predominance, yet its relationship with brain aging remains incompletely understood. Across the female lifespan, migraine interacts with neuroendocrine transitions, particularly menopause, a period characterized by substantial hormonal, metabolic, and neuroimmune changes. This hypothesis-driven narrative perspective synthesizes evidence across clinical, neuroimaging, and mechanistic domains to explore whether migraine, particularly in chronic or hormonally sensitive forms, may reflect altered neural vulnerability in a subset of women across midlife. A conceptual neuroendocrine framework is proposed in which recurrent migraine-related processes, including network stress, neuroinflammatory signaling, and bioenergetic demand, and altered sensory processing, may interact with estrogen-dependent regulatory mechanisms across adulthood. The menopausal transition, characterized by hormonal instability followed by sustained estrogen decline, may represent a period during which previously compensated neural differences become more clinically apparent. Evidence from neuroimaging and biomarker studies suggests partial overlap between migraine-related alterations and biological processes implicated in brain aging; however, findings remain heterogeneous and are not consistently linked to long-term cognitive outcomes. Within this framework, migraine is not interpreted as a deterministic or causal factor in…
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