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Effects of testosterone on visuospatial function and verbal fluency in postmenopausal women: results from a functional magnetic resonance imaging pilot study

Davis, Susan R. MBBS, FRACP, PhD1; Davison, Sonia L. MBBS, FRACP, PhD1; Gavrilescu, Maria PhD2; Searle, Karissa BSci (Hons)2; Gogos, Andrea PhD3,4; Rossell, Susan L. PhD5,6; Egan, Gary F. PhD3,7; Bell, Robin J. MBBS, PhD1

doi: 10.1097/GME.0b013e3182a065ed
Brief Reports

Objective This study aims to investigate the effects of testosterone on cognitive performance during functional magnetic resonance imaging (fMRI) in healthy estrogen-treated postmenopausal women.

Methods This was an open-label study in which postmenopausal women on nonoral estrogen therapy were treated with transdermal testosterone for 26 weeks. Women performed tests of verbal fluency (number of words) and mental rotation (reaction time and accuracy) during pretreatment and posttreatment fMRI. Blood oxygen level–dependent (BOLD) signal intensity was measured during fMRI tasks.

Results Nine women with a mean (SD) age of 55.4 (3.8) years completed the study. Twenty-six weeks of testosterone therapy was associated with significant decreases in BOLD intensity during the mental rotation task in the right superior parietal, left inferior parietal, and left precuneus regions, and during the verbal fluency task in the left inferior frontal gyrus, left lingual gyrus, and medial frontal gyrus (all P < 0.05), with no change in task performance, accuracy, or speed.

Conclusions Testosterone therapy is associated with reduced BOLD signal activation in key anatomical areas during fMRI verbal fluency and visuospatial tasks in healthy estrogen-treated postmenopausal women. Our interpretation is that testosterone therapy facilitates preservation of cognitive function with less neuronal recruitment.

From the 1Women’s Health Research Program, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; 2Howard Florey Institute and 3Center for Neuroscience, University of Melbourne, Parkville, Victoria, Australia; 4Mental Health Research Institute of Victoria, Parkville, Victoria, Australia; 5Monash-Alfred Psychiatry Research Center, Central Clinical School, Faculty of Medicine, Nursing, and Health Sciences, Alfred Hospital, Prahran, Victoria, Australia; 6Brain and Psychological Sciences Research Center, Swinburne University, Hawthorn, Victoria, Australia; and 7Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia.

Received April 18, 2013; revised and accepted June 11, 2013.

S.R.D. and S.L.D. are joint first authors.

Funding/support: This study was supported by an unrestricted research grant from FemPharm Pty Ltd (Melbourne, Australia), National Health and Medical Research Council of Australia grants 490938 and 465145, the Vincent Fairfax Family Foundation Fellowship, and the Royal Australasian College of Physicians Research and Education Foundation. S.R.D. is a principal research fellow of the National Health and Medical Research Council of Australia (grant 490938).

Australian clinical trials registry number: ACTRN12608000429358.

Financial disclosure/conflicts of interest: S.R.D. has received investigator-initiated research grant support from Biosante USA and Bayer Pharma AG; has acted as a consultant to Warner Chilcott, Biosante USA, and Trimel Canada; and is an investigator for Bayer Pharma AG and Trimel.

Address correspondence to: Susan R. Davis, MBBS, FRACP, PhD, Women’s Health Research Program, School of Public Health and Preventive Medicine, Monash University, Level 6, The Alfred Center, 99 Commercial Road, Melbourne, VIC 3004, Australia. E-mail:

© 2014 by The North American Menopause Society.