Adult growth hormone replacement: current understanding

Initial studies of growth hormone (GH) replacement in adults used weight- and surface area-based dosing regimes extrapolated from paediatric practice. Much of the beneficial effects were pharmacological rather than physiological. Furthermore, weight-based dosing regimens resulted in lower overall doses in females who require approximately threefold greater GH secretion in health to maintain a similar insulin-like growth factor-I level to males. This inequality of dosing explains studies reporting that males respond more efficaciously to GH replacement. Recent studies individualising GH doses to normalize serum insulin-like growth factor-I level have shown a similar spectra of beneficial effects to earlier weight-based studies; however, the degree of these effects on biological sequelea was reduced. Using this individualised dosing regimen, both genders responded equally to GH replacement for most biological end-points. The effect of GH replacement on bone mineral content is complex, and is dependent on the onset of GH deficiency, age of the patient and dosing regimen. GH is increasingly recognized as being intricately involved in regulation of surrogate markers of vascular risk and endothelial dysfunction, replacement of which normalises these indices. Definitive data on the effect of GH on mortality is awaited. Studies of 5-10 years duration suggest that beneficial effects of GH are maintained long-term. A depot preparation of GH is currently under investigation and, if proven to be efficacious and safe, might be a more acceptable therapy to a proportion of patients.