Growth Hormone in Athletes

Doping with growth hormone (GH) is a well-known problem both among elite athletes and among people training at gyms. It is mainly the anabolic and, to some extent, lipolytic effect of GH that is valued by its users. However, no reliable method to detect GH doping has been available, and the role of GH as an effective doping agent has been discussed. The aim of this thesis was to investigate markers of the GH/IGF-I axis and specific bone markers in athletes in connection with a maximum exercise test and longitudinally for one year, to validate the use of these markers in a forthcoming doping test for GH. Furthermore, the effects of one month’s administration of supraphysiological GH doses on body composition, exercise performance and IGFBP-4 and IGFBP-5 concentrations in well-trained healthy subjects were studied. The response to a maximum exercise test displayed a fairly uniform pattern, with peak concentrations of markers of the GH/IGF-I axis and bone markers immediately after exercise, followed by a subsequent decrease to baseline levels. The time to peak value for GH was significantly shorter for females compared with males. Some of the markers show strong evidence of high inter- or intra-individual variations in resting samples during one year, based on analyses focusing on the right tail of the distribution in relation to a normal distribution. Post-competition values differed from resting values for several of the GH/IGF-I axis and bone markers. Ranges for post competition values and for each marker in each gender at specific time points in connection with a maximum exercise test, are presented. The administration of supraphysiological doses of growth hormone for one month causes a dramatic increase in IGF-I levels, a reduction in body fat and an increase in the extracellular water volume. However, no significant increase in intracellular water volume was found, indicating limited anabolic effects by the supraphysiological GH doses. Administration of supraphysiological doses of GH during one month did not improve power output or oxygen uptake in a bicycle exercise test. Serum levels of IGFBP-4 and IGFBP-5 are increased by supraphysiological GH doses. Some of the effect of GH on IGFBP-4 and IGFBP-5 appears to be IGF-I dependent. However, the results do not support an obvious role for IGFBP-4 and IGFBP-5 as potential markers in a test for detecting GH doping. In conclusion, this thesis describes different aspects of markers of the GH/IGF-I axis and specific bone markers in connection to rest and exercise, to be used in a forthcoming test for GH doping, in which IGFBP-4 and IGFBP-5 do not seem to have a role. Finally, no obvious anabolic effects on body composition or performance-enhancing effects were seen with supraphysiological GH doses; thus, questioning the role of GH as a potent doping agent

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

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 carboxylterminal 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

Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential as a marker of GH abuse in sports: A double blind, placebo-controlled study

The effects of GH on bone remodeling in healthy adults have not been systematically investigated. An analysis of these effects might provide insights into GH physiology and might yield data useful for the detection of GH doping in sports. The aim of this study was to evaluate the effects of GH administration on biochemical markers of bone and collagen turnover in healthy volunteers. Ninety-nine healthy volunteers of both sexes were enrolled in a multicenter, randomized, double blind, placebo-controlled study and assigned to receive either placebo (40 subjects) or recombinant human GH (0.1 IU/kg day in 29 subjects and 0.2 IU/kg day in 30 subjects). The treatment duration was 28 days, followed by a 56-daywash-out period. The biochemical markers evaluated were the bone formation markers osteocalcin and C-terminal propeptide of type I procollagen, the resorption marker type I collagen telopeptide, and the soft tissue marker procollagen type III. All variables increased on days 21 and 28 in the two active treatment groups us. levels in both the baseline (P < 0.01) and placebo (P < 0.01) groups. The increment was more pronounced in the 0.2 IU/kg day group and remained significant on day 84 for procollagen type III (from 0.53 +/- 0.13 to 0.61 +/- 0.14 kU/L; P < 0.02) and osteocalcin (from 12.2 +/- 2.9 to 14.6 +/- 3.6 UG/L; P < 0.02), whereas levels of C-terminal propeptide of type I procollagen and type I collagen telopeptide declined after day 42 and were no longer significantly above baseline on day 84 (from 3.9 +/- 1.2 to 5.1 +/- 1.5 mu g/L and from 174 +/- 60 to 173 +/- 53 mu g/L, respectively). Gender-related differences were observed in the study; females were less responsive than males to GH administration with respect to procollagen type III and type I collagen telopeptide (P < 0.001). In conclusion, exogenous GH administration affects the biochemical parameters of bone and collagen turnover in a dose- and gender-dependent manner. As GH-induced modifications of most markers, in particular procollagen type III and osteocalcin, persist after GH withdrawal, they may be suitable markers for detecting GH abuse

The effect of four weeks of supraphysiological growth hormone administration on the insulin-like growth factor axis in women and men

Measurements of serum insulin-like growth factor I (IGF-I) and related markers are routinely used in the diagnosis and treatment of GH deficiency and excess. The validity of these markers for assessment of exogenous GH exposure in healthy adults is, however, unknown. We therefore conducted a double blind, placebo-controlled GH treatment trial in 99 healthy subjects [49 women and 50 men; mean +/- SE age, 25.6 +/- 0.6 (women)/25.7 +/- 0.6 yr (men)]. Blood was collected weekly during a 4-week treatment period (days 1-28), and the subjects were subsequently followed for additional 8 weeks (days 29-84). The treatment arms included: I) 0.1 IU/kg.day GH (n = 30; GK 0.1), II) 0.2 IU/kg.day GH (n = 29; GH 0.2), and III) placebo (n = 40). At baseline no gender-specific differences existed, except that the acidlabile subunit (ALS) levels were higher in females. Serum insulin-like growth factor I (IGF-I) levels in males receiving GH increased significantly through day 42 with no significant difference between the 2 doses. The absolute IGF-I response was significantly lower in females, and there was a clear dose-response relationship. ALS levels in males increased through day 30 (P < 0.001). In females ALS levels were only modestly increased on day 28 compared with those in the placebo group (P < 0.02). IGF-binding protein-3 (IGFBP-3) levels in males increased significantly in the GH 0.1 and the GH 0.2 groups on day 30 (P < 0.03), whereas no solid IGFBP-3 increase was detected in females. IGFBP-2 levels decreased insignificantly during GH exposure in both genders. A gender-specific upper normal range for each analyte was arbitrarily defined as 4 sn above the mean level at baseline. On the basis of IGF-I levels alone, GH exposure in the GH 0.2 group was detected in 86% of the males and in 50% of the females on day 21. On day 42 GK exposure was only weakly detectable in males and was not detectable in females. We conclude that 1) males are significantly more responsive than females to exogenous GH; 2) the increase in IGF-I is more robust compared with those in IGFBP-3 and ALS; 3) IGFBP-2 changes very little during GH treatment; and 4) among IGF related substances, IGF-I is the most specific marker of supraphysiological GH exposure