Human Growth Hormone (hGH)Recombinant human growth hormone rhGH has been on the list of forbidden substances since availability of its recombinant form improved in the early s. Although its effectiveness in enhancing physical performance is still unproved, the compound is likely used for its potential anabolic effect on the muscle growth, and also in combination with other products androgens, erythropoietin, etc. The degree of similarity between the endogenous and the recombinant forms, the pulsatile human growth hormone professional sports and marked interindividual can topical steroids cause immunosuppression makes detection of doping difficult. Two approaches proposed to overcome this problem are: This article gives an human growth hormone professional sports of what is presently known about hGH in relation to sport. The available methods of detection are also evaluated.
Growth hormone in sports - Wikipedia
Recombinant human growth hormone rhGH has been on the list of forbidden substances since availability of its recombinant form improved in the early s.
Although its effectiveness in enhancing physical performance is still unproved, the compound is likely used for its potential anabolic effect on the muscle growth, and also in combination with other products androgens, erythropoietin, etc. The degree of similarity between the endogenous and the recombinant forms, the pulsatile secretion and marked interindividual variability makes detection of doping difficult. Two approaches proposed to overcome this problem are: This article gives an overview of what is presently known about hGH in relation to sport.
The available methods of detection are also evaluated. Review of the literature on GH in relation to exercise, and its adverse effects and methods of detection when used for doping. The main effects of exercise on hGH production and the use and effects of rhGH in athletes are discussed.
Difficulties encountered by laboratories to prove misuse of this substance by both indirect and direct analyses are emphasised. The direct method currently seems to have the best reliability, even though the time window of detection is too short. To date the most promising method appears to be the direct approach utilising immunoassays. The human growth hormone hGH is a naturally occurring peptide hormone secreted by the pituitary gland.
In the late s, recombinant hGH rhGH was developed through genetic engineering and has been used with good results in the treatment of patients with hGH deficiency—allowing bone growth and impacting on the patient's final stature. Its misuse has been suspected in sport because of its anabolic properties.
Athletes and bodybuilders claim that hGH increases lean body mass and decreases the fat mass. The use of hGH in sport today is not only based on its anabolic properties, but also on its effect on carbohydrate and fat metabolism. International federations and the International Olympic Committee have had hGH on the list of forbidden compounds since , when it became obvious that the development of biotechnology products based on the recombination of DNA made hGH much more easily available on the regular and black markets.
The effect of acute exercise on production of GH in the body has been widely described in the literature. Furthermore, it appears that hGH response is more closely related to the peak intensity of exercise than the total work output. This appears evident when the training is very hard and above the aerobic threshold.
Thus, it is hard to differentiate between the physiological increase in hGH levels seen in exercise and what can be from external hGH administration as in doping. This problem makes the purely quantitative approach of measuring directly the total circulating GH not feasible in case of doping, except if the conditions of collection of biological samples are well controlled.
Somatotrope cells in the anterior pituitary secrete hGH in a pulsatile fashion. The secretion is regulated by two hypothalamic peptides, growth hormone releasing hormone, which stimulates hGH secretion, and somatostatin, which inhibits hGH secretion by back regulation. Secretion of hGH is slightly higher in women than in men, 11 with the highest levels observed at puberty. Human GH is prescribed for both childhood and adulthood hGH deficiency and for girls with Turner's syndrome.
High doses of hGH are used for relief from excessive burns or other thermal injuries. Since the late s, children with GH deficiency have been treated with hGH extracted from cadaver pituitary glands. Recently, due to the better availability of rhGH, hGH deficiency in adults has been recognised as a clinical syndrome and studied in clinical trials.
Long term GH administration studies have shown an increase in bone mass and persistence of the positive effects of hGH therapy. The positive effects on the body composition are essentially due the anabolic, lipolytic, and antinatriuretic properties of GH.
Among the effects that have been observed are: With therapeutic doses, no adverse side effects have been observed. GH has been considered as an ergogenic drug since the late s. The attractiveness of the product is based on popular knowledge that it is efficient, hard to detect, and without major side effects if well dosed.
GH misusers primarily try to benefit from the known anabolic action of the drug, to increase their muscle mass and power. GH is often taken in cycles of four to six weeks, as is the case for anabolic steroids in bodybuilding. In endurance sport, little is known about the optimum utilisation of hGH doping in combination with other products. It is highly individual and empirical. The effectiveness of rhGH in the improvement of sport performance is still under debate among users.
The positive effects described in hGH deficient adults are not that clear among athletes. Although many of these underground reports indicate some positive effect on muscle mass, it is difficult to differentiate benefits obtained when hGH is taken in combination with anabolic steroids or even if the hGH used was a less effective product.
The use of hGH as an anabolic agent still seems to be widespread, but it is difficult to investigate the extent of the phenomenon. Not only is the anabolic effect of hGH favored by high power output athletes, but its use is also gaining acceptance in endurance sport in combination with methods for enhancing oxygen transport.
As the results of controlled studies are generally not in agreement with subjective underground reports by misusers, it is difficult to draw any definite conclusions regarding the effects of excessive hGH administration on skeletal muscle function.
It must be stressed that the regimen of hGH use in sport is designed to fulfil purposes other than just an increase in athletes' muscle mass. The doses involved are certainly specific to a discipline, its training model, and tailored to the regimen of other ergogenic substances being used concurrently. Among these are the amino supplements such as arginine, ornithine, lysine, and tryptophan, but there are no clearly established results.
The effectiveness of rhGH is also widely discussed among its users in the underground literature or in internet chat rooms without a clear positive position.
Several aspects can be debated, but because of its price, some proportionality in the effects is to be expected by the users. There are few controlled studies on the effectiveness of GH on the performance of top level athletes. In general these studies have been performed with supraphysiological dosages but not with the large amounts claimed to be effective, for instance, by bodybuilders. The results of most of these controlled studies are generally less impressive than the claims of those who misuse the substance.
A study of volunteers under heavy resistance training found decrease of free fatty mass but no difference in the muscle strength. We believe that most of the time misusers will take rhGH as a part of their cocktail of specific preparations, rather than considering rhGH as a unique pharmaceutical preparation.
The effects of GH on the metabolism are so widespread that one can be certain that this is taken in combination with other products. And the final effect generally occurs elsewhere, rather than in what is tested in the laboratories. The long term risks of hGH use are not well known since epidemiological data regarding this type of treatment in healthy sportsmen are unavailable.
Acromegaly, which results from a pathological increase in endogenous production of GH, is often cited as one of the major risks associated with excessive use of hGH.
The major symptoms are swelling of the hands and feet, coarsened facial appearance, dentition problems, arthralgias, fluid retention, and excessive sweating. Acromegalic patients have an increased risk for diabetes mellitus and hypertension that can lead to premature mortality from cardiovascular diseases. There is also a risk of cardiomyopathy, osteoporosis, menstrual irregularities, and impotence. Some of these side effects are reversible after withdrawal of the drug.
Even though cadaveric GH is now rare in the black market, its use is associated with a high risk of developing Creutzfeldt—Jakob disease, which is characterised by slowly progressive dementia. The peptidic nature of the substance forced analysts to investigate other methods than those used in the classic analyses for anabolic steroids or stimulants with relatively low molecular weights.
Secretion of hGH by the pituitary gland is pulsatile, leading to highly fluctuating levels in the circulation. Moreover, hGH is considered to be a stress hormone regulated by factors such as sleep, nutritional status, exercise, and emotion.
Thus, there is high intraindividual and interindividual variability in the secretion of hGH. Quantifying the hormone itself is not sufficient to detect exogenous rhGH. More stable serum variables implied in the biological cascade produced by hGH secretion, or a doping application, may be the route of successful detection of hGH.
This hormone is used by some athletes in combination with either anabolic steroids to increase their muscle mass or EPO to increase their aerobic power. Detection of rhGH is still controversial, but it appears that the direct method based on the ratio of several circulating forms is the most promising one. Because of its convenient availability and relatively unlimited volume, attempts have been made to use urine for peptide detection.
For example, urine has been used for successful detection of EPO because of the glycosylated form of this hormone. The average urine concentration of hGH is between and times less than in blood. The lack of discrimination and specificity of the result made the urinary test less promising than a blood test.
Nevertheless, today, improvements in the organisation of target testing are quite obvious. It is considered feasible to do a urine test for GH in the morning, with an unannounced urine test outside any exercise session for other hormonal analyses. This may eventually be a solution for effective screening. Two main strategies are currently being followed to detect hGH doping using blood: A main objective of the study was to investigate the variation of these secondary variables during or after exercise.
These variables showed slight but significant changes after acute exercise. Moreover, the interindividual variability in the reaction to GH administration makes the use of indirect measurements almost impossible in a forensic description of GH misuse. It is obvious that rather than depending on the observation of a single value, a solution may be found in an algorithm combining all the biological variables from the cascade.
Nevertheless, all these investigations clearly show that the indirect approach can certainly be used for screening and targeting purposes when a biological follow up of athletes will be acceptable in the sport community.
But it cannot stand in front of a court as an absolute proof of doping. The regular evaluation of individual normal ranges in sportspeople could in fact lead to, as is currently done with haematological substances, better screening and targeting of the athletes and direct detection of hGH misuse as proposed in the following section.
The direct method of detection, based on double immunological tests needs to be well evaluated and validated. This review has described the difficulty sports authorities will face to prove hGH doping. At present, the short time window of detection of any method and the effect of exercise on natural hGH secretion still make any approach quite risky.
The proposed test was used during the Olympics in Athens and in Torino A second double sample test was used for confirmation purposes. It is thought that hGH doping, to be efficient, needs multiple injections.
Environmental influences, such as exercise, have been evaluated by Wallace et al. They concluded that all isoforms increased during exercise, peaked at the end, and declined after exercise. But it is considered that these changes will not invalidate the test after competition. Moreover, even if GH was used out of competition, this test should act a deterrent for its use.
Since the test was introduced in , no adverse analytical findings have been declared from any of the WADA laboratories that have validated the tests. A ratio is then calculated between the signal given by assay 1 to the signal given by assay 2.