Objective: Although epidemiological and clinical studies suggest that hormone replacement therapy (HRT) may protect against cognitive disorders and neurodegenerative diseases, the relation between estrogen and cognition in postmenopausal women remains controversial. Methods: In a double-blind placebo-controlled, parallel group design study the effects of HRT with the estrogen–progestogen combination Presomen 1.25 compositum® (1.25mg equine conjugated estrogens administered for 21 days plus the progestogen 5mg medrogeston given for 11 days) on event-related potentials (ERPs) in postmenopausal patients with age-related cognitive decline (DSM-IV code 780.9, ICD-10 code R 41.8) were investigated. After a pre-drug comparison with age-matched normal postmenopausal controls, 48 psychotropic drug-free patients aged 60 ± 6 years were randomized to receive either placebo or verum for 4 months. ERPs were recorded before as well as on the 91–92 days of the study, which thus fell into the estrogen phase of the treatment during the fourth cycle. Results: At baseline, patients showed a lengthening of P300 latency and an attenuation of P300 amplitudes as compared with normal controls. After HRT with Presomen, a significant shortening of P300 latency as compared with placebo was observed. Conclusions: The baseline P300 differences suggest that in the patient group the aging process was advanced, while after HRT with Presomen a significant improvement and normalization of information processing as indexed by P300 was observed.