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      Detecting growth hormone misuse in athletes

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          Abstract

          Athletes have been misusing growth hormone (GH) for its anabolic and metabolic effects since the early 1980s, at least a decade before endocrinologists began to treat adults with GH deficiency. Although there is an ongoing debate about whether GH is performance enhancing, recent studies suggest that GH improves strength and sprint capacity, particularly when combined with anabolic steroids. The detection of GH misuse is challenging because it is an endogenous hormone. Two approaches have been developed to detect GH misuse; the first is based on the measurement of pituitary GH isoforms and the ratio of 22-kDa isoform to total GH. The second is based on the measurement of insulin like growth factor-I (IGF-I) and N-terminal propeptide of type III procollagen (P-III-NP) which increase in a dose-dependent manner in response to GH administration. Both methodologies have been approved by the World Anti-Doping Agency (WADA) and have led to the detection of a number of athletes misusing GH.

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          Most cited references58

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          The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency.

          In a double-blind, placebo-controlled trial, we studied the effects of six months of growth hormone replacement in 24 adults with growth hormone deficiency. Most of the patients had acquired growth hormone deficiency during adulthood as a consequence of treatment for pituitary tumors, and all were receiving appropriate thyroid, adrenal, and gonadal hormone replacement. The daily dose of recombinant human growth hormone (rhGH) was 0.07 U per kilogram of body weight, given subcutaneously at bedtime. The mean (+/- SE) plasma concentration of insulin-like growth factor I increased from 0.41 +/- 0.05 to 1.53 +/- 0.16 U per liter during rhGH treatment. Treatment with rhGH had no effect on body weight. The mean lean body mass, however, increased by 5.5 +/- 1.1 kg (P less than 0.0001), and the fat mass decreased by 5.7 +/- 0.9 kg (P less than 0.0001) in the group treated with growth hormone; neither changed significantly in the placebo group. The basal metabolic rate, measured at base line and after one and six months of rhGH administration, increased significantly; the respective values were 32.4 +/- 1.4, 37.2 +/- 2.2, and 34.4 +/- 1.6 kcal per kilogram of lean body mass per day (P less than 0.001 for both comparisons). Fasting plasma cholesterol levels were lower (P less than 0.05) in the rhGH-treated group than in the placebo group, whereas plasma triglyceride values were similar in the two groups throughout the study. We conclude that growth hormone has a role in the regulation of body composition in adults, probably through its anabolic and lipolytic actions.
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            Growth hormone and the heart.

            Impaired cardiovascular function has recently been demonstrated to potentially reduce life expectancy both in GH deficiency and excess. Experimental and clinical studies have supported the evidence that GH and IGF-I are implicated in cardiac development. In most patients with acromegaly a specific cardiomyopathy, characterized by myocardial hypertrophy with interstitial fibrosis, lympho-mononuclear infiltration and areas of monocyte necrosis, results in biventricular concentric hypertrophy. In contrast, patients with childhood or adulthood-onset GH deficiency (GHD) may suffer both from structural cardiac abnormalities, such as narrowing of cardiac walls, and functional impairment, that combine to reduce diastolic filling and impair left ventricular response to peak exercise. In addition, GHD patients may have an increase in vascular intima-media thickness and a higher occurrence of atheromatous plaques, that can further aggravate the haemodynamic conditions and contribute to increased cardiovascular and cerebrovascular risk. However, several lines of evidence have suggested that the cardiovascular abnormalities can be partially reversed by suppressing GH and IGF-I levels in acromegaly or after GH replacement therapy in GHD patients. Recently, much attention has been focussed on the ability of GH to increase cardiac mass suggesting its possible use in the treatment of chronic nonendocrine heart failure. In fact, GH administration can induce an improvement in haemodynamic and clinical status in some patients. Although these data need to be confirmed in more extensive studies, such promising results seem to open new perspectives for GH treatment in humans.
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              Systematic review: the effects of growth hormone on athletic performance.

              Human growth hormone is reportedly used to enhance athletic performance, although its safety and efficacy for this purpose are poorly understood. To evaluate evidence about the effects of growth hormone on athletic performance in physically fit, young individuals. MEDLINE, EMBASE, SPORTDiscus, and Cochrane Collaboration databases were searched for English-language studies published between January 1966 and October 2007. Randomized, controlled trials that compared growth hormone treatment with no growth hormone treatment in community-dwelling healthy participants between 13 and 45 years of age. 2 authors independently reviewed articles and abstracted data. 44 articles describing 27 study samples met inclusion criteria; 303 participants received growth hormone, representing 13.3 person-years of treatment. Participants were young (mean age, 27 years [SD, 3]), lean (mean body mass index, 24 kg/m2 [SD, 2]), and physically fit (mean maximum oxygen uptake, 51 mL/kg of body weight per minute [SD, 8]). Growth hormone dosage (mean, 36 microg/kg per day [SD, 21]) and treatment duration (mean, 20 days [SD, 18] for studies giving growth hormone for >1 day) varied. Lean body mass increased in growth hormone recipients compared with participants who did not receive growth hormone (increase, 2.1 kg [95% CI, 1.3 to 2.9 kg]), but strength and exercise capacity did not seem to improve. Lactate levels during exercise were statistically significantly higher in 2 of 3 studies that evaluated this outcome. Growth hormone-treated participants more frequently experienced soft tissue edema and fatigue than did those not treated with growth hormone. Few studies evaluated athletic performance. Growth hormone protocols in the studies may not reflect real-world doses and regimens. Claims that growth hormone enhances physical performance are not supported by the scientific literature. Although the limited available evidence suggests that growth hormone increases lean body mass, it may not improve strength; in addition, it may worsen exercise capacity and increase adverse events. More research is needed to conclusively determine the effects of growth hormone on athletic performance.
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                Author and article information

                Journal
                Indian J Endocrinol Metab
                Indian J Endocrinol Metab
                IJEM
                Indian Journal of Endocrinology and Metabolism
                Medknow Publications & Media Pvt Ltd (India )
                2230-8210
                2230-9500
                October 2013
                : 17
                : Suppl1
                : S18-S22
                Affiliations
                [1] Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, UK
                Author notes
                Corresponding Author: Prof. Richard IG Holt, IDS Building (MP887), Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. E-mail: R.I.G.Holt@ 123456southampton.ac.uk
                Article
                IJEM-17-18
                10.4103/2230-8210.119494
                3830297
                24251151
                34e6f50a-0adc-40bf-81b0-8d6ca36dfe80
                Copyright: © Indian Journal of Endocrinology and Metabolism

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Review Article

                Endocrinology & Diabetes
                athletes,clinical trial,discriminant function,growth hormone,igf-i,misuse,performance,p-iii-np

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