The effects of 3-week estrogen hormone replacement on cognition in elderlyhealthy females

Rationale: Estrogen concentrations decline with age and menopause is often followed by an acceleration of the age effects on cognition. It is suggeste d that replacement of estrogen would reinstate, at least in part, cognitive abilities. Effects of estrogens on memory have been reported in studies wi th women in a clinical setting who either needed or wished to have the estr ogen replacement and are mostly in the perimenopausal age-band. Objective: The present study investigated the effects of estradiol on memory and on fr ontal lobe function in elderly female subjects who did not suffer any of th e postmenopausal symptoms and had never taken estrogen hormone replacement (EHR) previously. Methods: EHR (Progynova TS, transdermal estradiol; n=19) or placebo (n=18) was given for a period of 3 weeks to elderly healthy fema le subjects. Memory, frontal lobe functions (inhibition and planning) and v isuospatial abilities (mental rotation) were tested before and after treatm ent. Estrogen plasma levels were measured to confirm the result of EHR. Cor tisol plasma levels were also measured before and after cognitive performan ce in order to evaluate the effects of EHR on the sensitivity of the hypoth alamopituitary-adrenal (HPA) axis to mild mental stress. Results: Plasma es tradiol levels in the drug group increased to levels equivalent to that of a fertile woman (0.21+/-0.5 nmol/l). Memory function as well as visuospatia l abilities as measured by a mental rotation task improved significantly wi th EHR. However, there was no effect of EHR on frontal lobe functions. The cognitive effects were not dependent on an improvement in mood or general w ell-being as may be the case with EHR in women at peri- or post-menopausal stage. EHR was found to increase the HPA response to task-induced stress, a s indicated by an increase in cortisol plasma levels. Conclusions: The pres ent study has provided evidence of a beneficial effect of EHR on cognitive abilities given for first time to healthy elderly women. Furthermore, the p resent study has demonstrated a differential effect of EHR on memory, visuo spatial abilities and frontal lobe function.