HUMAN GROWTH HORMONE
Dr. Larry Weisenthal, Personal communication, 1999.
OBJECTIVE: IGF-I and IGF binding protein (IGFBP)-3 levels in man are positively regulated by GH status; in contrast, evidence suggests an inverse relationship between GH status and IGFBP-2. We investigated the effects of somatropin administration on the serum concentrations of these analytes, together with serum and urinary concentrations of GH, to evaluate their potential as markers in the development of a test for detecting doping with GH in sports competitors.
DESIGN: Somatropin was administered subcutaneously at a dose of 0.15 U/kg bodyweight/day at 1000 h for 3 days to eight healthy men (20-32 years old).
MEASUREMENTS: Serum concentrations of GH, IGF-I, IGFBP-2 and -3 were determined in blood samples collected at 1600 h on the days prior to (day -1), during (days 0, 1 and 2), and following administration (days 3 and 7). Urine was collected continuously from days -2 to 3 and then on day 7. RESULTS: Serum and urinary concentrations of GH were only raised on the days of administration whereas, following cessation of somatropin, the increases in the serum concentrations of IGF-I and IGFBP-3 were sustained for at least 1 day (30 h). Serum IGFBP-2 decreased during the period of administration and was still suppressed on day 3. The concentration ratios of IGFBP-3 to IGFBP-2 and IGF-I to IGFBP-2 increased markedly with administration and both ratios were still significantly augmented compared with basal values 30 h after the last administration.
CONCLUSION: With acute administration of somatropin to healthy men the serum concentration of IGFBP-2 decreases and the ratios of serum IGF-I/ IGFBP-2 and IGFBP-3/IGFBP-2 increase. These ratios should be considered in the development of a test for detecting somatropin administration in sport.
We report the results from blood sampling taken for the first time during doping control in athletics. The study includes samples from 99 athletes tested during IAAF-meetings in 1993-94. Blood doping with allogenic blood was not detected. The distribution of hemoglobin levels in athletes did not differ markedly from that found in controls. Erythropoietin (EPO) values were markedly lower in athletes than in controls, and 58% had EPO lower than the detection limit for the assay. This may be due to high-altitude residence before testing. Measurements of growth hormone (GH) and insulin-like growth factor 1 did not suggest GH-misuse in any athlete tested. One third of the male athletes had testosterone levels that were lower than the normal reference interval. This may at least partly be due to the combination of sampling at night and after strenuous exercise. One female athlete was found to have a grossly elevated testosterone level. In conclusion, the present results show the importance of taking into account the special circumstances during sampling when interpreting results from blood testing in athletes. Future research should focus on developing more sensitive and specific tests to detect doping with endogenous substances such as GH and EPO.
The 13C/12C isotope ratios have been measured for human pituitary growth hormone and three commercial growth hormone products in an attempt to differentiate endogenous versus exogenous origin. This might be a strategy to detect doping, as has recently been recognized for testosterone. While all preparations are statistically different from each other, we find that only Humatrope from Lilly has a carbon isotope ratio that is markedly different from those of human growth hormone or Genentech's Nutropin and Protropin. The low renal clearance of growth hormone reduces the applicability of this concept.
OBJECTIVE: To summarize the literature describing the epidemiology, pharmacology, efficacy, and adverse effects associated with growth hormone (GH), caffeine, aerobic metabolism facilitator (AMF), and sympathomimetic use among athletes.
DATA SOURCES: Relevant articles were identified from a MEDLINE search using the search terms "Doping in Sports," "Blood," "Caffeine," "Cocaine," "Erythropoietin," "Somatotropin," and "Sympathomimetics (exploded)." Additional references were found in bibliographies of these articles.
STUDY SELECTION/DATA EXTRACTION: We reviewed studies of ergogenic drug (ED) use among athletes. Interpretation of these studies is difficult because of poor research design and the paucity of information available. This necessitated the inclusion of many anecdotal or conjectural reports in our review.
DATA SYNTHESIS: There are no studies documenting an ergogenic effect associated with GH use in humans or animals. It is still unknown whether GH abuse causes adverse effects in healthy adults, although GH-induced acromegaly has been suspected. Amphetamines, cocaine, and caffeine are thought to improve performance via enhanced concentration among athletes. Amphetamines and cocaine may increase aggressiveness. The ergogenic effects of other sympathomimetics including ephedrine and phenylpropanolamine are unclear. AMFs (e.g., blood doping, epoetin) enhance aerobic metabolism and endurance by increasing the oxygen-carrying capacity of the blood. Risks associated with excessive AMF use include increased blood viscosity and clotting.
CONCLUSIONS: Athletes view EDs as an essential component for success. Without adequate intervention measures, ED abuse is likely to continue unchecked.
In 1989 the Medical Commission of the International Olympic Committee (IOC) introduced the new doping class of 'peptide hormones and analogues,' which include human chorionic gonadotrophin (hCG) and related compounds, adrenocorticotrophic hormone (ACTH), human growth hormone (hGH), all the releasing factors of these listed hormones, and erythropoietin (EPO). Currently there are no IOC approved definitive tests for these hormones but highly specific immunoassays combined with suitable purification techniques may be sufficient to warrant IOC approval. The importance of measuring hCG and luteinizing hormone (LH) in the control of testosterone misuse is discussed and strategies for the detection of hGH, ACTH and EPO administration are suggested.
It has been estimated that as many as 250,000 adolescents are using anabolic steroids (AS). Recently, anecdotal reports suggest that athletes may also be using human growth hormone (HGH). The purpose of the present study was to determine the following: 1) if adolescents in two suburban midwestern high schools (83% white, 14% Asian, and 3% black) were using HGH; 2) knowledge of its effects; 3) reasons for use; and 4) concurrent AS use. After we obtained informed written consent, 224 male and 208 female 10th-grade students were surveyed using a 15-item questionnaire. Of male students surveyed, 5% (n = 11) reported past or present use of HGH, and one female student reported use. Our data suggest that among male adolescents surveyed, a majority had heard of this substance, and 31% of males reported knowing someone who was using HGH. Chi-square analysis found a significant association between AS and HGH use where seven AS users reported past or present use of HGH. Most HGH users were unaware of its side effects and reported first use between 14 and 15 years of age. No differences in sports activity, ethnicity, or age were found between users and nonusers of HGH.
Growth hormone is a powerful anabolic hormone that affects all body systems and plays an important role in muscle growth. It is released from the anterior pituitary in response to a variety of stimuli including exercise, sleep, stress, and the administration of a variety of drugs and amino acids. Serum levels are variable and are dependent on such factors as age, sex, body composition and level of fitness. Animal experiments have shown that growth hormone can partially reverse surgically induced muscle atrophy and weakness. Growth hormone administration to normal animals leads to muscle hypertrophy, but this muscular growth is not accompanied by increased strength. Growth hormone excess leads to acromegaly, a disease with significant morbidity, including a myopathy in which muscles appear larger but are functionally weaker. Although there is no scientific evidence documenting an improvement in athletic performance following growth hormone supplementation, it is reported that this practice is becoming more widespread among athletes wishing to avoid detection with current doping control measures. There are anecdotal reports that athletes are injecting cadaveric or biosynthetic forms of growth hormone, both of which are associated with potentially serious complications. In addition, some athletes are ingesting drugs and amino acids in the belief that their endogenous growth hormone secretion will be increased. There have been no scientific studies on the effects of growth hormone supplementation, and the anecdotal reports have been equivocal, with some individuals reporting spectacular results while others report no change. Despite the lack of valid evidence for its efficacy and its potentially serious side effects, it has been predicted that growth hormone use may increase. Growth hormone use and abuse has the potential to dramatically change the future conduct of athletics and may prove to be a threat to the concept of fair competition.
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