Cognition in women - the effect of testosterone on the cognitive abilities of women investigated via functional Magnetic Resonance Imaging

The lifetime risk of dementia in women is double that of men, and it has been hypothesised that differences in endogenous androgen levels (male hormones, including testosterone) may contribute to this sex difference. Women and men perform differently in tests of cognitive function (brain function, including memory), and women with higher testosterone levels have performed better on specific cognitive tasks compared to those with lower levels. Testosterone levels decline in women with advancing age, such that there is a 50percent reduction between age 20 and 40 years. Preliminary studies suggest that testosterone administration to women may enhance cognitive performance, even in the acute setting. Mild cognitive impairment is predictive of dementia, yet subtle changes in cognition are difficult to detect using standardised tests, which are prone to a learning effect. This study will assess the effects of 6 months of daily transdermal (skin spray) testosterone administration on cognition in postmenopausal women aged 45 to 60 years, and to determine the time course to any changes identified. The study will be based at the Womens Health Program, Central and Eastern Clinical School, Alfred Hospital, Victoria, and each participant will be required to attend 5 visits. Sensitive tests of cognitive function (CogState) will be utilised in order to attempt to identify even minor changes in cognition. In addition, functional magnetic resonance imaging (fMRI) will allow cognitive testing to occur within the MRI scanner, such that anatomical localisation of any effects of testosterone administration within the brain is possible. The cognitive tasks administered whilst in the scanner will assess verbal fluency, executive functioning, and mental rotation ability. CogState will occur at weeks 0, 12 and 26 whilst the fMRI testing will occur at weeks 0 and 26. Blood tests for testosterone levels will be taken at the screening visit and then at weeks 6, 12 and 26. This study will serve as a pilot study prior to a randomised placebo-controlled study of the effects of testosterone administration in postmenopausal women. Ultimately if testosterone is found to enhance cognitive function in women, it may be a future therapeutic option in postmenopausal women at high risk of developingdementia.