Toward the development of a test for growth hormone (GH) abuse: a study of extreme physiological ranges of GH-dependent markers in 813 elite athletes in the postcompetition setting.
ABSTRACT There is a need to develop a test to detect GH abuse by elite athletes. Measured levels of GH in blood or urine, however, provide little information on the GH-IGF-I axis. Previous studies have identified a series of indirect markers of GH action that are markedly altered by the administration of GH, but to a lesser degree by acute exercise. This study was undertaken to determine the physiological range of these GH-dependent variables in elite athletes after a competitive event to determine whether such values differ from resting values in normal and athletic subjects and to establish whether any adjustments to this range are required on the basis of age, gender, demographic characteristics, or the nature of the exercise performed. Serum samples were collected from 813 elite athletes (537 males and 276 females; age range, 17-64 yr) from 15 sporting disciplines within 2 h of completion of a major competitive event. IGF-I, IGF-binding protein 2 (IGFBP-2), IGFBP-3, acid-labile subunit, and the bone and soft tissue markers, osteocalcin, carboxyl-terminal propeptide of type I procollagen, carboxyl-terminal cross-linked telopeptide of type I collagen, and procollagen type III were measured. Sporting category, gender, age, height, weight, body mass index (BMI), and racial group of the athlete were documented, and results were compared both to normative data and to values obtained from elite athletes under resting conditions. Forty-one percent of IGF-I values in male athletes and 41% of values in female athletes were above the upper limits of 99% reference ranges derived from resting values in a normal population. Postcompetition levels of all variables except carboxyl-terminal propeptide of type I procollagen and carboxyl-terminal cross-linked telopeptide of type I collagen differed from resting values. There was a consistent age-dependent fall in measured levels of all variables (P < 0.0001) with the exception of IGFBP-2, which increased with age (P < 0.0001). BMI, but not height, exerted a small, but significant, influence on several variables. After adjustment for age, there were no significant differences in the levels of any of the measured variables between sporting categories. IGFBP-2 and IGFBP-3 were lower in 35 black athletes compared with those in 35 white athletes matched for age, gender, height, BMI, and sporting category. We have demonstrated that there are predictable age-dependent levels of GH-dependent markers in elite athletes that are consistent even at the extremes of physical exertion and that these are independent of sporting category. Normative data applicable to white athletes are provided. This provides important groundwork for the development of a test for GH abuse, although these values may be specific for the reagents and assays used.
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ABSTRACT: Key PointsThe relationship between age and physiological function remains poorly defined and there are no physiological markers that can be used to reliably predict the age of an individual.This could be due to a variety of confounding genetic and lifestyle factors, and in particular to ill-defined and low levels of physical activity.This study assessed the relationship between age and a diverse range of physiological functions in a cohort of highly active older individuals (cyclists) aged 55–79 years in whom the effects of lifestyle factors would be ameliorated.Significant associations between age and function were observed for many functions. was most closely associated with age, but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual.The data suggest that the relationship between human ageing and physiological function is highly individualistic and modified by inactivity.AbstractDespite extensive research, the relationship between age and physiological function remains poorly characterised and there are currently no reliable markers of human ageing. This is probably due to a number of confounding factors, particularly in studies of a cross-sectional nature. These include inter-subject genetic variation, as well as inter-generational differences in nutrition, healthcare and insufficient levels of physical activity as well as other environmental factors. We have studied a cohort of highly and homogeneously active older male (n = 84) and female (n = 41) cyclists aged 55–79 years who it is proposed represent a model for the study of human ageing free from the majority of confounding factors, especially inactivity. The aim of the study was to identify physiological markers of ageing by assessing the relationship between function and age across a wide range of indices. Each participant underwent a detailed physiological profiling which included measures of cardiovascular, respiratory, neuromuscular, metabolic, endocrine and cognitive functions, bone strength, and health and well-being. Significant associations between age and function were observed for many functions. The maximal rate of oxygen consumption ( showed the closest association with age (r = −0.443 to −0.664; P < 0.001), but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual. The results of this cross-sectional study suggest that even when many confounding variables are removed the relationship between function and healthy ageing is complex and likely to be highly individualistic and that physical activity levels must be taken into account in ageing studies.The Journal of Physiology 01/2015; · 4.38 Impact Factor
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ABSTRACT: To athletes, insulin-like growth factor-I (IGF-I) is an attractive performance-enhancing drug, particularly as an alternative to growth hormone (GH) because IGF-I mediates many of the anabolic actions of GH. IGF-I has beneficial effects on muscle protein synthesis and glycogen storage that could enhance performance in several sporting disciplines. Recombinant human IGF-I (rhIGF-I) is used in clinical practice, but a variety of IGF-I compounds and IGF-I analogues are also advertised on the internet and many have been available on the black market for several years. Although methods for detecting GH misuse are now well established and there have been several cases in which athletes have tested positive for GH, no test is yet in place for detecting IGF-I misuse. The GH-2004 research group has been investigating methods for detection of IGF-I misuse and a test is being developed on the basis of the principles of the successful GH-2000 marker method, in which markers from the IGF axis and markers of collagen and bone turnover are used to detect GH misuse. Commercial immunoassays for these markers have been validated for anti-doping purposes but new methods, including IGF-I measurement by use of mass spectrometry, should improve the performance of the tests and help in the detection of athletes who are doping with these peptide hormones.Analytical and Bioanalytical Chemistry 08/2013; · 3.66 Impact Factor
Article: Growth hormone doping: a review.[Show abstract] [Hide abstract]
ABSTRACT: The use of growth hormone (GH) as a performance enhancing substance was first promoted in lay publications, long before scientists fully acknowledged its benefits. It is thought athletes currently use GH to enhance their athletic performance and to accelerate the healing of sporting injuries. Over recent years, a number of high profile athletes have admitted to using GH. To date, there is only limited and weak evidence for its beneficial effects on performance. Nevertheless the "hype" around its effectiveness and the lack of a foolproof detection methodology that will detect its abuse longer than 24 hours after the last injection has encouraged its widespread use. This article reviews the current evidence of the ergogenic effects of GH along with the risks associated with its use. The review also examines methodologies, both currently available and in development for detecting its abuse.Open Access Journal of Sports Medicine 01/2011; 2:99-111.