Migraine and menopause as converging factors in brain vulnerability: a hypothesis-driven perspective
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
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 neurode
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 neurodegeneration, but rather as a potential clinical indicator of context-dependent alterations in neural vulnerability influenced by comorbidities, hormonal factors, and individual resilience. The proposed model is exploratory and highlights the need for longitudinal and mechanistic studies to clarify whether migraine-related features have relevance for long-term brain health. By integrating perspectives from neuroscience, endocrinology, and pain research, this work aims to generate testable hypotheses and to support further development of sex-informed approaches to studying brain aging in women. Abs1