Abstract: The aim of this study was to provide a comprehensive review on hormone-based pathophysiology of aging of the optic nerve and glaucoma, including a literature review and expert opinions. Glaucoma, a group of intraocular pressure-related optic neuropathies, is characterized by the slow progressive neurodegeneration of retinal ganglion cells and their axons, resulting in irreversible visual sensitivity loss and blindness. Increasing evidence suggests that glaucoma represents the accelerated aging of the optic nerve and is a neurodegenerative disease of the central nervous system. This review highlights the high burden of glaucoma in older women and the importance of understanding the hormone-related pathophysiology of optic nerve aging and glaucoma in women. Strong epidemiological, clinical, and experimental evidence supports the proposed hypothesis that early loss of estrogen leads to premature aging and increased susceptibility of the optic nerve to glaucomatous damage. Future investigations into the hormone-related mechanisms of aging and glaucoma will support the development of novel sex-specific preventive and therapeutic strategies in glaucoma.