This 2025 mini-review from Brown University examines how dysfunction of the hypothalamic-pituitary-ovarian (HPO) axis in conditions like menopause, primary ovarian insufficiency (POI), and polycystic ovary syndrome (PCOS) elevates risk for cognitive decline and neurodegeneration. Beyond the well-known neuroprotective role of estradiol, the authors highlight underappreciated contributions of elevated gonadotropins—particularly FSH and LH—to neurodegenerative pathology. They also explore how systemic inflammation acts as an additional HPO axis disruptor. The review calls for a multisystem research approach and argues that hormone replacement therapy targeting only estrogen is insufficient to address brain aging risks in women with ovarian disorders.
