Assessing the Effects of Dehydroepiandrosterone Replacement on the Mood of Adrenalectomised/Hypoadrenal Subjects

The role of dehydroepiandosterone (DHEA) and its sulphated ester (DHEAS) [together known as DHEA(S)] in humans remains to be fully elucidated. They are the most abundant circulating steroid hormones in humans with the principle source of production being the adrenal glands. In adrenalectomised or hypoadrenal subjects it is not standard clinical practice to replace this hormone. Whilst this lack of DHEA(S) is clearly not life threatening, the published literature on the psychological effects of replacement in this population has shown some benefit in quality of life but data concerning the metabolic effects is conflicting and incomplete. We wish to carry out a study to measure the effect of DHEA(S) replacement in a group of adrenalectomised / hypoadrenal subjects and measure the outcome of a number of psychological and metabolic parameters both prior to and after twelve weeks of 50 mg/day DHEA(S) in a double blind randomised cross over design.

Mood, quality of life and sexual well being will be assessed using validated questionnaires. In addition, we will utilise the GCRC facility to measure body composition using total body water and DEXA. We will measure insulin sensitivity, exercise performance, muscle fatigability and VO2 max. Pre- and post- intervention muscle biopsies will assess DHEA(S) effects on myosin heavy chain isoform expression; skeletal muscle mitochondrial ATP production and be used to assess muscle enzyme levels.