Objective: to determine whether the decline of testosterone during ageing would make this nucleus more vulnerable for NF changes (i.e. hyperphosphorylated-tau) in men, or that the decline of estrogens in the postmenopausal period would protect the infundibular nucleus in women. Methods: We investigated the infundibular nucleus in postmortem subjects. Brain materials obtained from 29 subjects in the Netherlands Brain Bank were further classified as control subjects and subjects with abnormal hormone conditions. Procedures consisted of tissue collection, immunochemical staining, and analysis of the staining intensity. Results then were collected and concluded using observational methods. Results: Elderly male subjects with low testosterone conditions showed more severe NF changes in the infundibular nucleus than postmenopausal women. The occurrence of NF changes in elderly subjects was generally accompanied by the presence of basket-like nerve terminals staining for ERÎ². Conclusion: The sex difference in NF changes in the infundibular nucleus in the elderly is due to hyperphosphorylated-tau induction in low testosterone and ageing condition in men, while in postmenopausal women the declining estrogen levels seem to protect against NF changes in this brain area.