Short-term transdermal estradiol therapy, cognition and depressive symptoms in healthy older women. A randomised placebo controlled pilot cross-over study.

The potential role of estrogen in protecting women from cognitive decline and reducing depressive symptoms is of great therapeutic interest. In a pilot randomised placebo controlled cross-over study, we aimed to determine the short-term effects of transdermal estradiol therapy on cognition and depressive symptoms in healthy cognitively normal post-menopausal women over 60 years of age. Nineteen cognitively normal women, without clinical depression whom had undergone a hysterectomy in the past were recruited. Women were randomised to receive either transdermal estradiol 50 microg/24 h (Femseven) or transdermal placebo for 12 weeks before crossing over to the other medication for a further 12 weeks. Cognition was assessed every 6 weeks by the cognitive drug research (CDR) computerised assessment which recorded both accuracy and speed in the following cognitive tests; simple reaction time, choice reaction time, digit vigilance, visual tracking, spatial working memory, immediate and delayed word recall and delayed face and picture recall. Depressive symptoms were measured using the brief assessment scale depression card (BASDEC) depression rating scale at baseline, 12 and 24 weeks. Participants had a mean age of 71, IQ of 115 and MMSE of 29. Simple reaction time and the BASDEC depression rating scale improved after 12 weeks of estradiol use. All other tests were unaltered by estradiol. Twelve weeks of transdermal estradiol therapy did not consistently improve the speed or accuracy of older women in various cognitive tests. However, the results do support the concept that depressive symptoms may be reduced by estradiol, and not simply due to the relief of climacteric symptoms.