Accumulating evidence suggests that estrogen deficiency contributes to the pathogenesis of depression via multiple interconnected mechanisms, including dysregulation of monoamine neurotransmission, hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, decreased brain-derived neurotrophic factor (BDNF) expression, impaired mitochondrial function and bioenergetics, neuroinflammation mediated by glial cells, and disruption of gut-brain axis communication. Here, BDNF is linked to major depressive disorder.