Abstract
Athletes have enjoyed almost a thirty year amnesty of rhGH abuse, which they consider has contributed to the winning of medals and the breaking of world records. Such a reprieve is almost at an end, since WADA have identified a method to detect rhGH abuse. Or have they?
The anecdotal word “on the street” is that rhGH is still undetectable and athletes believe that the benefits, at the dosages they administer, far outweigh the risks!
Since the availability of GH, athletes have been trying to extrapolate these effects from the deficiency state to the healthy corpus and increase their sporting prowess.
Past confessions from athletes, such as Ben Johnson, Kelly White, Tim Montgomery, Marion Jones and currently Dwain Chambers have demonstrated that they are prepared to tread the very fine lines that separate the “men from the boys”. Rewards are so great, that anonymous surveys have identified that athletes will risk ill health, if they believe they can cheat, win and not get caught.
The question that still needs to be answered is, “does growth hormone enhance performance”?
Recent research suggests that it could. There is also a suspicion that in “cycled” low supraphysiological doses, it is no where near as harmful as WADA claim it to be.
Introduction
Since the isolation of human growth hormone (GH) by Li and Papkoff [1] and the synthesis of recombinant human growth hormone (rhGH) by recombinant DNA technology in the late 1970s [2], sportspersons have been trying to extrapolate the proven benefits of replacement therapy in GH deficiency (GHD) to promote athletic supremacy, in competition [3].
Physical exercise is a “knife edge” physiological state of homeostasis, which the elite athlete aspires to tip the balance in favour of anabolism.
Contemporary evidence appears to contradict the proven anabolic effect of rhGH in deficiency, in drug naïve healthy human muscle, that could improve athletic performance [4], [5], [6]. Administration of rhGH causes no further increase in muscle mass or strength, than that provided by resistance training in healthy young athletes [7], [8], [9], [10].
Difficulties arise in targeting an appropriate dose range in such subjects, given the cardiovascular and metabolic hazards involved and the associated ethical issues.
A supraphysiological effect of rhGH on muscle in athletes is comparable with the early pathological effects of acromegaly, which can initiate a GH resistant state. In acromegaly, true muscle hypertrophy cannot be evaluated in a sporting context, since acromegaly is only identified when the pathology becomes fulminant. It is only at this stage that such patients come under the auspices and management of clinicians, with little or no knowledge or experience of its application to sport.
Despite no overt proof of performance enhancement, the use of rhGH in “sport” has increased dramatically from 6% [11] to 24% [12] over a 5 year period. The question is why?
The USA Federal investigation into the shenanigans of the Bay Area Laboratory Co-operative (BALCO) in the provision of the sublingual “designer steroid” tetrahydrogestrinone (THG) coded as ‘The Clear’ which was supplied to high profile athletes [13]. The “Mitchell Report” has provided us with some of the clues [14]. The BALCO affair, attracted media attention not least because of the supply of THG but also the supply of a transdermal preparation, ‘The Cream’, that contained testosterone (T) and epitestosterone (E), produced specifically to evade a doping T/E ratio urinalysis.
The “Mitchell Report”, released in 2007, covers the history of the use of illegal performance-enhancing substances by players in the Major League Baseball (MLB) Joint Drug Prevention and Treatment Program.
According to the report, after mandatory random testing began in 2004, rhGH became the substance of choice among players, as it is not detectable in tests. Also, it was noted that at least one player from each of the thirty MLB teams was involved in the alleged violations.
The office of the New York Attorney General has estimated that fraudulent sales of human growth hormone and other prescription drugs have amounted to 10% of New York’s $3 billion in Medicaid drug expenses in 2002.
The “Mitchell Report” identified that rhGH was the substance most frequently sold to players by Kirk Radomski, a former New York mets clubhouse employee who was a significant source of illegal performance-enhancing substances until late 2005.
Also many players have purchased rhGH through “anti-aging” centres using dubious prescriptions written by physicians who have never examined, nor even met, the “customers” for whom they were writing prescriptions.
In February 2007, a government task force executed search warrants on “Signature Compounding Pharmacy”, in Orlando, Florida and other businesses, including several so-called “rejuvenation centres”, exposing another source of illegal performance-enhancing substances.
The Food and Drug Administration (FDA) does not approve the use of rhGH to treat an athletic injury, to become leaner, nor to improve athletic performance. Its use is a violation of federal law if it is not for an authorised purpose, even if a legitimate prescription is provided.
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Section snippets
The beneficial effect of rhGH in athletes
The knowledge that multiple studies have demonstrated a decreased psychological well-being in hypopituitary patients, despite replacement with all hormones but GH [15] has been applied to the sporting arena.
The first researchers experimented on athletes using biosynthetic N-methionyl hGH (met-hGH), consisting of 192 amino acids, as opposed to rhGH (191 amino acids). The administration of met-hGH (2.67 mg 3 days per week) for 6 weeks in 8 well-trained exercising adults, with an age range of 22–33
The effects of different dosages of rhGH
Despite supraphysiological dosages of rhGH being administered to drug naïve athletes, approximating acromegalic levels of GH, no performance enhancement has been identified by the scientific community. It is possible that the cohort sizes used by researchers, to date, have been too low to achieve the results that are still anecdotally claimed to be as a result of self-administration. Professional bodybuilders and power lifters are believed to administer dosages of the hormone, up to 0.066 mg kg−1
Beneficial effects of rhGH in GH resistant states
When rhGH is given in conjunction with the corticosteroid, prednisone, it counteracts the protein catabolic effects of prednisone in healthy volunteers and results in increased whole body protein synthesis rates, with no effect on proteolysis [28].
The infusion of rhGH over 24 h causes a net glutamine release from skeletal muscle into the circulation and increased glutamine synthetase messenger ribonucleic acid (mRNA) levels. This could compensate for reduced glutamine precursor availability,
Recent studies in simulated catabolic states in sport
With the knowledge that physical exercise may result in catabolism, if optimum conditions are not adhered to and despite the knowledge that sportspersons may be abusing very high dosages of rhGH, studies have been conducted in a simulated catabolic state in apparently healthy sportspersons.
A cohort of 24 abstinent androgenic-anabolic steroid (AAS) using males administering 0.019 mg kg−1 day−1 rhGH, a comparatively small supraphysiological dose, were compared with a cohort of 24 abstinent AAS using
What makes rhGH the anabolic agent to abuse?
The major actions of GH are that it is a very potent anabolic agent, promoting protein synthesis and simultaneous lipolysis. These benefits are commonly acknowledged in sport.
It probably stimulates protein synthesis through mobilisation of amino acid transporters in a similar manner to insulin and glucose transporters [57].
In the optimum nutritional and training environment, rhGH may enhance constructive skeletal muscle development, to a supraphysiological status. This is a genuine belief by
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Where applicable, the experiments described received approval for the investigations from an institutional human research committee here and conform with the principles of the World Medical Association’s Declaration of Helsinki, 1975.View full text
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