The effects of 3-weeks estrogen hormone replacement on cognition in elderly healthy females

Rationale: Estrogen concentrations decline with age and menopause is often followed by an acceleration of the age effects on cognition. It is suggested that replacement of estrogen would reinstate, at least in part, cognitive abilities. Effects of estrogens on memory have been reported in studies with women in a clinical setting who either needed or wished to have the estrogen replacement and are mostly in the perimenopausal age-band. Objective: The present study investigated the effects of estradiol on memory and on frontal lobe function in elderly female subjects who did not suffer any of the 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 female subjects. Memory, frontal lobe functions (inhibition and planning) and visuospatial abilities (mental rotation) were tested before and after treatment. Estrogen plasma levels were measured to confirm the result of EHR. Cortisol plasma levels were also measured before and after cognitive performance in order to evaluate the effects of EHR on the sensitivity of the hypothalamopituitary-adrenal (HPA) axis to mild mental stress. Results: Plasma estradiol 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 visuospatial abilities as measured by a mental rotation task improved significantly with 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 well-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, as indicated by an increase in cortisol plasma levels. Conclusions: The present study has provided evidence of a beneficial effect of EHR on cognitive abilities given for first time to healthy elderly women. Furthermore, the present study has demonstrated a differential effect of EHR on memory, visuospatial abilities and frontal lobe function.