5 How much, and by what mechanisms, does growth hormone replacement improve the quality of life in GH-deficient adults?

The majority of studies (but not all) have demonstrated that adults with hypopituitarism of both childhood and adult onset have a diminished quality of life (QOL) in comparison with the normal population. Reductions in physical and mental energy, dissatisfaction with body image and poor memory have been reported most consistently. A specific role for growth hormone (GH) deficiency, as opposed to multiple pituitary hormone deficiency, has been observed for the memory deficit, which extends to both short-and long-term momory. Comparisons with normal siblings have confirmed the reduced QOL, although differences have been small. There is less consensus for a reduction in QOL when hypopituitary subjects are compared with patients with other chronic diseases, with studies supporting (in comparison with diabetics) and refuting (in comparison with patients following mastoid surgery) the reduction in QOL. GH replacement in adult has improved QOL, particularly in the domains of energy level and self-esteem, and memory has improved. The social impact of these changes may be considerable, with patients requiring fewer days' sick leave. A major placebo effect is present, however, and neutral results as well as positive have been reported in placebo-controlled trials. Where a positive effect has been observed, it has been more likely to occur in patients with a low QOL at the outset. It is otherwise impossible to predict at the outset those who will benefit from GH replacement. GH treatment has effects on body composition, exercise capacity, muscle strength, total body water and intermediary metabolism which would be expected to improve QOL. Replacement therapy also has side-effects, and it is the variable balance of the positive and negative effects, coupled with the difficulties of measuring QOL, which have led to the disparate results in the literature. There is probably also a true inter-individual variation, although the mechanisms of this are currently unknown.