Maturitas 54 (2006) 222–228 Effects of estrogens on cognition and brain morphology: Involvement of the cerebellum R. Ghidoni a , M. Boccardi b , L. Benussi a , C. Testa b , A. Villa a , M. Pievani b , L. Gigola a , F. Sabattoli b , L. Barbiero a , G.B. Frisoni b , G. Binetti a,∗ a NeuroBioGen Lab-Memory Clinic, IRCCS “Centro San Giovanni di Dio-Fatebenefratelli”, Brescia, Italy b Laboratory of Epidemiology Neuroimaging and Telemedicine (LENITEM), IRCCS “Centro San Giovanni di Dio-Fatebenefratelli”, Brescia, Italy Received 15 April 2005; received in revised form 31 October 2005; accepted 3 November 2005 Abstract Objectives: Sex steroid hormones are implicated in the cognitive processes of the adult brain. Among studies reporting a positive effect of estrogen replacement therapy (ERT) on cognition, the most consistent evidence is that it enhances verbal memory and visuospatial functions. In the present study we investigated the effect of ERT on cognition and on brain morphology in healthy postmenopausal women, taking into account the distinction in current and past ERT users. Methods: Participants were postmenopausal nondemented women recruited from the community: ERT users were 40 (23 current users, 17 past users), while never users were 43. Forty of recruited subjects gave consent to undergo 3D high resolution MRI (16 current users, 7 past users and 17 never users). Participants underwent MMSE and a battery of neuropsychological tests measuring memory, language, intelligence, attention and visuo-spatial abilities. Results: The past users group outperformed the never users in four tests: Token test, WCST categories, attentional matrices and Rey’s delayed list; the current users group outperformed the never users in the Rey’s list test. ERT users had greater grey matter volumes mainly in the cerebellum, but an increase was observed also in the parietal and occipital cortex. Conclusions: ERT use appears to improve linguistic, attentive and planning abilities. Interestingly, the beneficial effects on cognition were detected mainly in the past users subgroup. Here we propose that the trophic effect of estrogens on cerebellum might account for the observed improvement in cognition. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: ERT; Aging; Cognition; Cerebellum; Brain morphology ∗ Corresponding author at: NeuroBioGen Lab-Memory Clinic, IRCCS “Centro San Giovanni di Dio-Fatebenefratelli”, via Pilas- troni 4, 25125 Brescia, Italy. Tel.: +39 030 3501709; fax: +39 030 3533513. E-mail address: gbinetti@fatebenefratelli.it (G. Binetti). 1. Introduction Declining in cognitive function is a growing pub- lic health concern for older adults, given the well- documented pattern of age-associated decrements in many areas of cognitive performance and the increasing 0378-5122/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.maturitas.2005.11.002