Purpose:We investigated the effect of menopausal duration on cognitive function using adjunctive hormone replacement therapy(HRT) in postmenopausal women with depression. Method:Twelve postmenopausal women with depressive disorder were enrolled. Six patients having menopausal duration of less than 3 years was assigned to the short duration group and six patients of more than 3 years to the long duration group. Each patient was treated with conjugated equine estrogen(1.25mg) plus medroxyprogesterone(5mg) for 8 weeks. Cognitive performance was measured by the Verbal Memory Test, Visual Memory Test, Trail Making Test, Digit Symbol Test, and Attention Shift Test. The Beck Depression Inventory was used for evaluation of depressed mood. The reproductive hormone levels were also measured. Results:The long duration group showed the lower performance only in Trail Making Test B compared with the short duration group at baseline. After 8 weeks, the long duration group performed significantly better in the Trail Making Test B compared with the short duration group. The differences in change of depressive mood and gonadal hormone level between two groups were not significant. Conclusion:Menopausal duration before HRT may influence the effect of estrogen on cognition in some cognitive domains. This might be related with estrogen receptor hypersensitivity which induced by the longer estrogen deficiency.