AAS, growth hormone, and insulin abuse Figure 2 The growth hormone somatropin, in its correct 22-kD-hGH form.Three-dimensional structure, generated from the protein data base SWISS PROT. Structural data supplied with the help of the program RasMol.The n-terminal amino acid (at the bottom left hand corner) is marked yellow, as are the disulphide bridges (and the sequence range missing on the 20 kDa hGH variant).The ranges with an α-Helix-structure are marked in red. induces cell proliferation and is thought to inhibit apoptosis (O’Reilly et al 2006). IGF-binding proteins (IGFBP) and their proteases regulate the access of ligands to the IGF-I receptor affecting its action. Levels of IGF-I are at their peak during late ado- lescence and decline throughout adulthood, mirror imaging hGH (Milani et al 2004). IGF-I levels reﬂect the secretory activity of growth hormone and are one of a potential num- ber of markers for identiﬁcation of hGH-deﬁciency (GHD), hGH-excess (acromegaly), or rhGH administration in sport (Powrie et al 2007). In conjunction with hGH, IGF-I has varying differential effects on protein, glucose, lipid, and calcium metabolism and therefore body composition (Mauras and Haymond 2005). Growth hormone, anxiety, and depression Much of our knowledge of the psychological effects of hGH has been learned from the GHD model. Using the Not- tingham Health Proﬁle (NHP) and the Psychological Well- being Schedule (PGWS), hGH replacement for 6 months in deﬁcient adults has been shown to improve mental state and quality of life (QoL), such as mood and energy levels, (McGauley 1989). GHD adults have been noted to have a disturbed sleep pattern, which returns to normal on rhGH replacement (Aström et al 1990). Decreased psychologi- cal well-being has been reported in hypopituitary patients Therapeutics and Clinical Risk Management 2008:4(3) despite pituitary replacement with all hormones but growth hormone (Stabler et al 1992). HGH replacement in GHD has been shown to improve emotional control and well-being, accompanied by lower scores on anxiety, in adult males with altered body image (underestimated body size), low self- esteem and depression (Riva and Molinari 1995). Interest- ingly, the hGH response to physiological stimuli is reduced in healthy young males with higher psychometrically measured depressiveness (Harro et al 1999) and depressed patients have a blunted hGH response to hGH releasing hormone (Dahl et al 2000). Consequently there has been an increasing attraction in hormone replacement therapy to improve health and QoL of the healthy elderly, with age-related decline in hormone levels, the somatopause (Savine and Sonksen 2000). A new 21-item age-related hormonal decline (A-RHDQoL) questionnaire is an individualized questionnaire measuring perceived impact of age-related hormonal decline in the QoL of older males. The internal consistency reliability and content validity of the A-RHDQoL are established, but the measure is at an early stage of its development and its sen- sitivity to change and other psychometric properties needs to be evaluated in clinical trials of hormone replacement in older males (McMillan et al 2003). Discontinuation of rhGH treatment of young adults with GHD and then recommencing treatment, demonstrated that intra-subject IGF-I levels were negatively correlated with depression, fatigue, tension, and anxiety and positively with vigor and memory (Stouthart 589