The neurobiology of menopause: Implications for brain aging and Alzheimer's risk

A growing body of evidence implicates the menopausal transition as a neurobiological inflection point in women's brain aging and Alzheimer's disease (AD) vulnerability. Menopause is a midlife neuroendocrine transition characterized by a decline in sex steroid hormones and widespread systemic effects. The brain is not a passive recipient of ovarian hormones but an active endocrine-sensing organ. Menopause, however, does not act in isolation: the ovarian-brain axis is established embryonically, activated at puberty, remodeled during pregnancy and postpartum, and reconfigured during the menopausal transition, with implications for later-life brain aging. This review places menopause within a lifespan neuroendocrine framework, examining mechanisms by which the transition may influence the brain, including altered hormone signaling, bioenergetics, synaptic plasticity, neurovascular function, inflammation, and AD-related pathology. It then reviews evidence linking menopausal timing to neurobiological and AD vulnerability, discusses estrogen therapy, and considers menopause as a biologically plausible window for risk stratification and prevention.