Graham et al and during exercise in 6 endurance-trained athletes versus 5 controls, with a mean age of 31 years, measuring whole body leucine turnover. Plasma levels of glycerol and free fatty acids and glycerol rate of appearance (Ra) at rest, during and post exercise increased during rhGH treatment compared with placebo. Glucose Ra and glucose rate of disappearance (Rd) were greater during rhGH treatment compared with placebo (Healy et al 2003). Resting energy expenditure and fat oxidation were greater under resting conditions during rhGH treatment compared with placebo, in 9 males with a mean age of 24 years, a weight of 77.3 kg, body fat of 17.7%, and a V˙O2 peak 37.9 ml.kg−1.min−1, who completed 6 × 30-minute randomly assigned cycle ergometry exercise trials. An rhGH infusion (0.01 mg.kg−1, [~2.3 IU]) was followed by a 30-minute exercise trial. There were no signiﬁcant condition effects for total work, caloric expenditure, heart-rate response, the blood lactate response, or ratings of perceived exertion response (RPE). However, acute rhGH administration resulted in lower V˙O2 peak without a drop-off in power output (Irving et al 2004). The reduced V˙O2 peak may be explained by the rhGH administration improving exercise economy. This may have been as a consequence of production of free fatty acids (FFA) by rhGH’s lipolytic effect, providing the substrates for the maintenance of energy metabolism, despite the lower V˙O2 peak. There was no increase observed in the strength in 30 physically active and healthy individuals of both genders with a mean age 25.9 years. Ten subjects each received rhGH (0.033 mg.kg−1.day−1) or rhGH (0.067 mg.kg−1.day−1) or placebo for 1 month. IGF-I signiﬁcantly increased by 134%, and there were signiﬁcant increases observed for body weight (2.7%), LBM (5.3%), total body water (6.5%), and extracellular water (ECW) (9.6%). Body fat signiﬁcantly decreased by 6.6% (Ehrnborg et al 2005). There was no increase in power or V˙O2 peak in 30 physically active and healthy individuals of both gen- ders, with a mean age of 26 years who received rhGH (0.033 mg.kg−1.day−1) or rhGH (0.067 mg.kg−1.day−1) or placebo for 1 month (Berggren et al 2005). Plasma levels of glycerol and free fatty acids increased at rest and during exercise during rhGH administration (0.067 mg.kg−1.day−1) for 4 weeks, in 6 trained male athletes compared with controls. This had the effect of increasing resting energy expenditure and fat oxidation and increasing glucose production and uptake after exercise (Healy et al 2006). Six days of rhGH administration (0.019 mg.kg−1.day−1 [~5 IU.day−1]) by 24 abstinent male AAS-users, with a 592 mean age of 32 years compared with controls, increased forced expiratory volume in one second/forced vital capac- ity (FEV1/FVC), maximum inspiratory pressure, maximum expiratory pressure, and V˙O2 peak (Graham et al 2007b). It is possible that previous use of AAS, had increased the num- ber of myonuclei per muscle ﬁber, to such an extent that a 12-week washout program was an insufﬁcient time interval for return of the proportion of central nuclei to baseline (Eriksson et al 2005). Athletes continue to abuse both cadaver pituitary hGH and rhGH in the belief that such effects can be extrapolated to the healthy individual (Crist et al 1988; Deyssig et al 1993). The abuse of cadaver pituitary hGH has diminished in Europe, subsequent to its association with Jacob-Creutzfeldt disease and the abundant Internet availability of rhGH from China. The acclaim of the anabolic properties of growth hormone appeared in the underground doping literature as early as 1983 (Duchaine 1983). Its abuse has increased (Baker et al 2006) despite early research demonstrating its effect on functional abilities, is no greater than exercise alone in healthy young males (Yarasheki et al 1992) or elderly males (Yarasheki et al 1995) and the demonstration that supraphysiological dosages can have fatal consequences (Takala et al 1999). Both hGH and rhGH are believed to stimulate production of class-1 isoforms of IGF-I locally in muscles and tendons. These may have a preventative effect on rupture of muscles and tendons in AAS-induced hypertrophy (Doessing and Kjaer 2005). The transmission of force from muscle ﬁbres to bone, could be explained by the stimulating effect of hGH on collagen synthesis. Such strengthened connective tissue would provide a more strain-resistant musculo-tendinous junction and could explain why there is still a claimed effect of rhGH on athletic performance. Previous studies in humans have not shown an increase in endurance exercise or strength in drug naive young athletes, solitarily due to rhGH, but it has been suggested that such differences were not signiﬁcant due to a lack of power, given the relatively small sample sizes. The relevance of these effects for athletic performance would suggest enhancement under circumstances where an athlete cycles AAS and then administers rhGH in the abstinent phase in an attempt to circumvent a doping violation. Physiology and biochemistry of Insulin Insulin is a 2 chain (30 and 21 amino-acids) polypeptide hor- mone (51 amino-acids, 5808 molecular weight) synthesized and secreted by the beta-cells of the islets of Langerhans in Therapeutics and Clinical Risk Management 2008:4(3)