Early and Premature Menopause and Brain Health Across the Adult Lifespan: A Scoping Review of Neuroimaging and Neuropathological Outcomes

Early onset menopause may have detrimental impacts on brain health, yet mechanisms underlying this association are poorly understood. This scoping review aimed to synthesize findings linking early and premature menopause to brain health across adulthood including brain volume, function, and pathology. We conducted a scoping review using Covidence systematic review software with a comprehensive search strategy using search terms related to early and premature menopause and brain health outcomes. Authors independently mapped study details onto a data-extraction tool to ensure inter-rater agreement. We reviewed 21 studies sorted into two categories by primary exposure: 1) early age at menopause (n=10), and 2) premenopausal bilateral salpingo-oophorectomy (PBSO) (n=11). Nine of 10 papers focused on early age at menopause reported at least one association with poorer brain outcomes, including smaller volumes and greater pathology. Brain regions reported to be associated with earlier menopause age in multiple studies included medial temporal lobe (i.e., hippocampus, and parahippocampus). Multiple studies observed associations with lower total gray matter and poorer white matter integrity. Among papers focused on PBSO, 7 reported worse brain outcomes and 4 originating from the same parent study reported unclear associations (i.e., group differences were attributable to estrogen use, age, or other factors besides PBSO). Despite inconsistency in definitions, methodologies, and populations of interest, over three-quarters of papers we reviewed reported poorer brain health associated with premature and early menopause. Future research would benefit from studies designed to evaluate underlying neural mechanisms and increased measurement accuracy for menopause type and timing.