Graham et al Figure 1Testosterone is a steroid hormone from the androgen group.It is the principal male sex hormone and the “original” anabolic steroid. often with significant co-morbidity (Gruber and Pope 2000). Fifty six percent demonstrated hypomania during the “administration-phase” and 40% reported depressive symptoms during withdrawal. These athletes also displayed several psychiatric syndromes, previously ill-deﬁned, such as obsessive compulsive disorder (OCD), rigid dietary practice, nontraditional gender roles, and chronic dissat- isfaction and preoccupation with their physiques (muscle dysmorphia). Pagonis and colleagues (2006b) has shown in a study of 160 AAS-abusing athletes compared with 160 placebo and controls that the wide range of psychiatric side effects induced by the abuse of AAS is correlated to the severity of abuse. The force of these side effects intensiﬁes as the abuse escalates. The latest substances being abused by individuals, associ- ated with sport, include recombinant human growth hormone (rhGH) or rhGH in combination with insulin (Sonksen 2001; Rennie 2003). Both are being used as ergogenic aids and as doping agents. They are currently taken in the belief that they increase skeletal muscle mass and improve performance (Jenkins 2001). In Gruber and Pope’s study (1999), 14% of surveyed subjects also abused insulin and AAS. Insulin has a shorter history as a ‘doping agent’ when compared with both GH and AAS (Sonksen 2001). The use of AAS, rhGH, and insulin in the UK in bodybuilding and other sports has increased (Baker et al 2006) compared with a survey in 2001 (Grace et al 2001). AAS use has increased by 17%, insulin by 6%, and rhGH by 18%. Unless caught by urinalysis in the act, convicting a competitive sporting individual who has taken rhGH (Powrie et al 2007) and insulin (Coghlan 2001) is not possible. Insulin in acute abuse is inﬁnitely more danger- ous than rhGH. The few cases that have been published 588 are case histories of individuals who have been admitted to hospital following accidental insulin overdose (Konrad et al 1998; Rich et al 1998; Evans and Lynch 2003). They have a distorted body image and reported the condition of “reverse anorexia”, where they believed they were small and weak, despite being large and muscular (Pope et al 1993). The reasons for use of these anabolic agents appear to be based not only on peer review, but also scientiﬁc research (Sonksen 2001). Low self-esteem and unrealistic, muscular male body ideals, puts individuals at risk for negative body images and unhealthy eating and exercise habits. These individuals resort to drug-taking to counteract their altered body images. The legislation in the UK would appear to be permissive in allowing the bodybuilding fraternity no prob- lems in obtaining their insulin supplies (Elkin et al 1997). Dawson (2001) identiﬁed that 10% of 450 patients attending a needle exchange programme self-prescribed insulin for nontherapeutic purposes. Physiological and biochemical aspects of growth hormone The ability of the somatotroph cells in the anterior pituitary to synthesize and secrete the polypeptide, hGH, is determined by a gene called the Prophet of Pit-1 (PROP1). When hGH is translated, 70%–80% is secreted as a 191-amino-acid, 4-helix bundle protein, and 20%–30% as a less abundant 176-amino-acid form (Baumann 1991; Wu et al 1999) (Figure 2). Hypothalamic-releasing and hypothalamic- inhibiting hormones acting via the hypophysial portal system control the secretion of hGH, which is secreted into the circulation (Melmed 2006). In healthy persons, the hGH level is usually 0.2 µ g.L−1 throughout most of the day. There are approximately 10–12 intermittent secretory bursts in a 24 hour period, mostly at night, when the level can rise to as much as 30 µ g.L−1 (Melmed 2006). HGH secretion declines at 14% per decade from the age of 20 years (Iranmanesh et al 1991). HGH action is mediated by an hGH receptor, which is expressed mainly in the liver and is composed of dimers that change conformation when occupied by an hGH ligand (Brown et al 2005). Cleavage of the hGH receptor provides a circulating hGH binding protein (GHBP), prolonging the half-life and mediat- ing the transport of hGH (Argetsinger et al 1993). Intracellular hGH signalling is decreased by suppres- sors of cytokine signaling. HGH induces the synthesis of peripheral insulin-like growth factor I (IGF-I) (Le Roith et al 2001) while endocrine, autocrine, and paracrine IGF-I Therapeutics and Clinical Risk Management 2008:4(3)