Graham et al et al 2003). A large proportion of GHD adults complain of low energy levels, emotional lability, and mental fatigue and have an impaired QoL, and psychiatric morbidity, which improves after one month of growth hormone treatment (Mahajan et al 2004). The Hospital Anxiety and Depression Scale (HADS) questionnaire is a simple, reliable tool for use in medical practice (Zigmond and Snaith 1983) and has been used to determine the disturbed emotional state of groups of psychosomatic patients (Karakula et al 1996). HADS scores screen for psychiatric morbidity (Janson et al 1994), predicts psychosocial and physical outcome (Herrmann 1997), and have been used extensively with high validity in psychiatric outpatients (Martin et al 2003). This information is freely available to informed individuals in the recreational ﬁtness industry and elite sport who wish to improve their physiques (Baker et al 2006). Such individuals who abuse AAS, rhGH, and insulin, are aware that rhGH increases fat loss and that insulin prevents proteolysis, as a consequence they abuse both these hormones either alone or in combination, with or without AAS. Effects of hGH on anthropometry, strength, and exercise performance RhGH administration has therapeutic value as a replacement therapy for GHD adults, increasing lean body mass (LBM) and reducing total and visceral fat (Johannsson et al 1997). Aerobic performance (V˙O2 peak) increased in GHD and reversed following cessation (Gullestad et al 1997). Five years of rhGH replacement therapy in elderly adults with GHD normalized knee ﬂexor strength, knee extensor strength, and handgrip strength (Gotherstrom et al 2005). rhGH increases lipid mobilization and oxidation, decreasing protein oxidation and increasing protein synthesis (Horber and Haymond 1990). The use of acipimox (an antilipolytic) with rhGH administration in a 37-hour fasting state, which eliminated the ability of hGH to restrict fasting protein loss, indicated that stimulation of lipolysis by hGH is its principle protein- conserving mechanism (Nørrelund et al 2003). Such effects are associated with signiﬁcantly increased lean body mass and have been translated into signiﬁcantly increased aerobic performance (Liu et al 2003). Myostatin, a cytokine impli- cated in differentiated skeletal muscle growth, is a member of the transforming growth factor-beta (TGFß) family that has gained attention due to its remarkable expression proﬁle and dramatic actions. Myostatin messenger-ribonuceleic acid (mRNA) expression is signiﬁcantly inhibited by rhGH. Myostatin mRNA expression was signiﬁcantly inhibited to 590 31% by rhGH, compared with controls and sustained after 18 months, signiﬁcantly increasing V˙O2 peak, in GHD (Liu et al 2003). In humans, hyper-catabolic states such as human immunodeﬁciency virus (HIV) associated wasting, have been categorised by marked upregulation of myostatin (Gonzalez- Cadavid et al 1998). Reproduction of such results has not been forthcoming in healthy young adults, but has been identiﬁed in an infant with a mutation of the myostatin gene and was associated with gross muscle hypertrophy (Schuelke et al 2004). Effects in apparently healthy individuals The ﬁrst researchers experimented on athletes using bio- synthetic methionyl hGH (met-hGH), consisting of 192 amino-acids, as opposed to recombinant hGH, consisting of 191 amino acids (Crist et al 1988). Met-hGH (2.67 mg [~8 IU] 3 days per week) for 6 weeks in 8 well-trained exercising adults (22–33 years of age) who trained with progressive resistance exercise significantly decreased body fat and signiﬁcantly increased LBM. Five sub- jects had a suppressed hGH response to stimulation from either L-dopa, arginine or sub-maximal exercise (Crist et al 1988). One might postulate that rhGH administration would beneﬁt elderly males, decreasing adiposity and increasing LBM (principally muscle). Rudman and colleagues (1990, 1991) demonstrated such evidence. However, they did not demonstrate increased strength. Acute administration of either rhGH, or IGF-I, in normal healthy humans in the post-absorptive state, signiﬁcantly increased forearm net balance of amino acids (Fryburg et al 1991). The effects are claimed to occur through the stimulation of protein synthesis rather than decreased protein breakdown. However, increased LBM does not appear to have been translated into increased strength or power in young healthy individuals who have never previously used per- formance-enhancing drugs. For example, administration of rhGH appears to cause no further increase in muscle mass or strength than provided by resistance training in any healthy young athletes with a mean age of 23 years (Crist et al 1988; Yarasheki et al 1992, 1993; Deyssig 1993) or indeed in healthy elderly males with a mean age of 67 years (Taaffe et al 1994; Yarasheki et al 1995). There has been no substantial evidence that it can increase strength in healthy males and females greater than sixty years of age (Zachwieja and Yarasheki 1999). The rate of protein synthesis, identiﬁed as the rate of incorporation of amino acids labelled with stable isotopes into Therapeutics and Clinical Risk Management 2008:4(3)