Mild Cognitive Impairment in Men Following Androgen Deprivation

MCI with ageing is thought in part to be related to reduced serum sex hormones which is well-recognised, especially in females, but poorly understood. International studies assessing hormone replacement therapy (HRT) to prevent/reduce MCI are ongoing. MCI leads to morbidity, reduced quality of life and substantial healthcare costs. The commonest therapeutically induced reduction in sex hormone level in men is treatment of prostate cancer (PCa). PCa is androgen dependent and androgen-deprivation therapy (ADT) suppressing testosterone to castrate levels is key therapy for advanced disease. About one million men worldwide have received ADT for PCa, mostly using luteinising hormone releasing-hormone agonists (LHRHa) although oral oestrogens were used in the past; eventually perhaps 4% of Caucasians may be castrated. MCI as a side-effect of castration in men remains poorly researched. This pilot study will quantify the extent of MCI in men receiving ADT with LHRHa and oestrogen to inform the design of a larger study to understand mechanisms, predict affected patients and determine ways of reducing MCI. Researching relationships of sex hormones and MCI should improve understanding and interventions for slowing/preventing MCI in PCa survivors. HRT in women slows MCI. Alternatives for ADT include parenteral oestrogen. The PATCH clinical trial comparing transdermal oestrogen with LHRHa offers an opportunity to assess oestrogen as preventative for male MCI. Functional magnetic resonance imaging (fMRI), quantitative electroencephalography (qEEG) and neuropsychological tests will be used to test this hypothesis.