Growth hormone, IGF-I and insulin and their abuse in sport / R.I.G. Holt, P.H. Sönksen. - (British Journal of Pharmacology 154 (2008) 3 (June); p. 542-556)

• PMID: 18376417
• PMCID: PMC2439509
• DOI: 10.1038/bjp.2008.99

Abstract

There is widespread anecdotal evidence that growth hormone (GH) is used by athletes for its anabolic and lipolytic properties. Although there is little evidence that GH improves performance in young healthy adults, randomized controlled studies carried out so far are inadequately designed to demonstrate this, not least because GH is often abused in combination with anabolic steroids and insulin. Some of the anabolic actions of GH are mediated through the generation of insulin-like growth factor-I (IGF-I), and it is believed that this is also being abused. Athletes are exposing themselves to potential harm by self-administering large doses of GH, IGF-I and insulin. The effects of excess GH are exemplified by acromegaly. IGF-I may mediate and cause some of these changes, but in addition, IGF-I may lead to profound hypoglycaemia, as indeed can insulin. Although GH is on the World Anti-doping Agency list of banned substances, the detection of abuse with GH is challenging. Two approaches have been developed to detect GH abuse. The first is based on an assessment of the effect of exogenous recombinant human GH on pituitary GH isoforms and the second is based on the measurement of markers of GH action. As a result, GH abuse can be detected with reasonable sensitivity and specificity. Testing for IGF-I and insulin is in its infancy, but the measurement of markers of GH action may also detect IGF-I usage, while urine mass spectroscopy has begun to identify the use of insulin analogues.

Detecting autologous blood transfusions: a comparison of three passport approaches and four blood markers / J. Mørkeberg, K. Sharpe, B. Belhage, R. Damsgaard, W. Schmidt, N. Prommer, C.J. Gore, M.J. Ashenden. - (Scandinavian journal of medicine & science in sports 21 (2011) 2 (April); p. 235-243)

• PMID: 19903320
• DOI: 10.1111/j.1600-0838.2009.01033.x

Abstract

Blood passport has been suggested as an indirect tool to detect various kinds of blood manipulations. Autologous blood transfusions are currently undetectable, and the objective of this study was to examine the sensitivities of different blood markers and blood passport approaches in order to determine the best approach to detect autologous blood transfusions. Twenty-nine subjects were transfused with either one (n=8) or three (n=21) bags of autologous blood. Hemoglobin concentration ([Hb]), percentage of reticulocytes (%ret) and hemoglobin mass (Hbmass) were measured 1 day before reinfusion and six times after reinfusion. The sensitivity and specificity of a novel marker, Hbmr (based on Hbmass and %ret), was evaluated together with [Hb], Hbmass and OFF-hr by different passport methods. Our novel Hbmr marker showed superior sensitivity in detecting the highest dosage of transfused blood, with OFF-hr showing equal or superior sensitivities at lower dosages. Hbmr and OFF-hr showed superior but equal sensitivities from 1 to 4 weeks after transfusion compared with [Hb] and Hbmass, with Hbmass being the only tenable prospect to detect acute transfusions. Because autologous blood transfusions can be an acute practice with blood withdrawal and reinfusion within a few days, Hbmass seems to be the only option for revealing this practice.

Biochemistry, physiology, and complications of blood doping: facts and speculation / Giuseppe Lippi, Massimo Franchini, Gian Luca Salvagno, Gian Cesare Guidi. - (Critical Reviews in Clinical Laboratory Sciences 43 (2006) 4; p. 349-391)

• PMID: 16769597
• DOI: 10.1080/10408360600755313

Abstract

Competition is a natural part of human nature. Techniques and substances employed to enhance athletic performance and to achieve unfair success in sport have a long history, and there has been little knowledge or acceptance of potential harmful effects. Among doping practices, blood doping has become an integral part of endurance sport disciplines over the past decade. The definition of blood doping includes methods or substances administered for non-medical reasons to healthy athletes for improving aerobic performance. It includes all means aimed at producing an increased or more efficient mechanism of oxygen transport and delivery to peripheral tissues and muscles. The aim of this review is to discuss the biochemistry, physiology, and complications of blood doping and to provide an update on current antidoping policies.

Erythropoiesis-stimulating agents and other methods to enhance oxygen transport / S. Elliott. - (British Journal of Pharmacology 154 (2008) 3 (June); p. 529-541). - Special Issue: Themed Section: Drugs in Sport: Guest Editors: Professor J.C. McGrath and Professor D.A. Cowan

• PMID: 18362898
• PMCID: PMC2439521
• DOI: 10.1038/bjp.2008.89

Abstract

Oxygen is essential for life, and the body has developed an exquisite method to collect oxygen in the lungs and transport it to the tissues. Hb contained within red blood cells (RBCs), is the key oxygen-carrying component in blood, and levels of RBCs are tightly controlled according to demand for oxygen. The availability of oxygen plays a critical role in athletic performance, and agents that enhance oxygen delivery to tissues increase aerobic power. Early methods to increase oxygen delivery included training at altitude, and later, transfusion of packed RBCs. A breakthrough in understanding how RBC formation is controlled included the discovery of erythropoietin (Epo) and cloning of the EPO gene. Cloning of the EPO gene was followed by commercial development of recombinant human Epo (rHuEpo). Legitimate use of this and other agents that affect oxygen delivery is important in the treatment of anaemia (low Hb levels) in patients with chronic kidney disease or in cancer patients with chemotherapy-induced anaemia. However, competitive sports was affected by illicit use of rHuEpo to enhance performance. Testing methods for these agents resulted in a cat-and-mouse game, with testing labs attempting to detect the use of a drug or blood product to improve athletic performance (doping) and certain athletes developing methods to use the agents without being detected. This article examines the current methods to enhance aerobic performance and the methods to detect illicit use.

Blood doping : infusions, erythropoietin and artificial blood / E. Randy Eichner. - (Sports Medicine 37 (2007) 4-5 (April); p. 389-391)

• PMID: 17465616
• DOI: 10.2165/00007256-200737040-00030

Abstract

As science marches on, athletes and coaches march close behind. Researchers have long been interested in how red cell mass and blood volume affect exercise capacity. Interest in blood doping soared after the 1968 Mexico City Olympics. Studies in the 1970s and 1980s suggested that transfusing red cells could speed endurance performance. Diverse athletes of the time were accused of blood doping. In the late 1980s, recombinant human erythropoietin (EPO) began to supplant transfusion for doping. EPO use is a suspect in nearly 20 deaths in 4 years in European cyclists. In the 1998 Tour de France, a team was ejected for using EPO and six other teams quit the race. The beat goes on; in recent years, diverse endurance and sprint athletes have been caught or accused of using EPO. Tests to detect EPO are improving but are not yet foolproof. As EPO tests improve, blood transfusion is back in vogue and some athletes may have infused artificial blood. Tests for detecting artificial blood also exist, but it seems it will take widespread, year-round, unannounced, out-of-competition testing and stern penalties to deter blood doping.

Factors influencing the steroid profile in doping control analysis / Ute Mareck, Hans Geyer, Georg Opfermann, Mario Thevis, Wilhelm Schänzer. - (Journal of Mass Spectrometry 43 (2008) 7 (July); p. 877-891)

• PMID: 18570179
• DOI: 10.1002/jms.1457

Abstract

Steroid profiling is one of the most versatile and informative screening tools for the detection of steroid abuse in sports drug testing. Concentrations and ratios of various endogenously produced steroidal hormones, their precursors and metabolites including testosterone (T), epitestosterone (E), dihydrotestosterone (DHT), androsterone (And), etiocholanolone (Etio), dehydroepiandrosterone (DHEA), 5alpha-androstane-3alpha,17beta-diol (Adiol), and 5beta-androstane-3alpha,17beta-diol (Bdiol) as well as androstenedione, 6alpha-OH-androstenedione, 5beta-androstane-3alpha,17alpha-diol (17-epi-Bdiol), 5alpha-androstane-3alpha,17alpha-diol (17-epi-Adiol), 3alpha,5-cyclo-5alpha-androstan-6beta-ol-17-one (3alpha,5-cyclo), 5alpha-androstanedione (Adion), and 5beta-androstanedione (Bdion) add up to a steroid profile that is highly sensitive to applications of endogenous as well as synthetic anabolic steroids, masking agents, and bacterial activity. Hence, the knowledge of factors that do influence the steroid profile pattern is a central aspect, and pharmaceutical (application of endogenous steroids and various pharmaceutical preparations), technical (hydrolysis, derivatization, matrix), and biological (bacterial activities, enzyme side activities) issues are reviewed.

Exploring the potential ergogenic effects of glycerol hyperhydration / Jeff L. Nelson, Robert A. Robergs. - (Sports Medicine 37 (2007) 11; p. 981-1000)

• PMID: 17953468
• DOI: 10.2165/00007256-200737110-00005

Abstract

During athletic competition or recreational pursuits, a body's hydration level can become compromised, resulting in a decrement in performance. Glycerol (1,2,3-propanetriol) has been used to induce hyperhydration in an attempt to offset the deleterious effects of dehydration. When glycerol is consumed orally, it is rapidly absorbed primarily in the small intestine. It is reported to be evenly distributed among all fluid compartments, with the exception of the cerebral spinal fluid and aqueous humour, and promotes hyperhydration by inducing an osmotic gradient. Through an increase in the kidney's medullary concentration gradient, water absorption in the nephron is enhanced. When glycerol is consumed, the plasma glycerol concentration increases in proportion to the dose ingested, which easily exceeds the glycerol saturation point resulting in urinary glycerol excretion. Thus, without supplemental glycerol ingestion, there will be a decrease in the osmotic gradient resulting in a loss of hyperhydration. The ergogenic nature of glycerol has been investigated as to its effect on fluid retention, thermoregulation, cardiovascular responses and performance. While many studies provide evidence of hyperhydration, others do not. Only two studies reviewed showed a thermoregulatory advantage. Furthermore, the preponderance of evidence neither weighed for or against cardiovascular or performance advantages. What makes one study provide favourable results while another study does not is unclear. Possible explanations may include subject characteristics, environmental factors, research design, whether fluids with or without glycerol were given during exercise, the rate at which fluids are initially given to induce hyperhydration, the time between peak hyperhydration/peak plasma glycerol concentration and the trial (i.e. exercise), the glycerol dose (i.e. 1.0 g/kg body mass) and what it is based upon, the percentage glycerol solution (i.e. 5%, 20%), the variation of time between the end of the hydration protocol and the beginning of exercise, or perhaps the intensity of exercise (fixed, variable, percentage maximum oxygen uptake). What is clear is that glycerol has the capacity to enhance fluid retention. In so doing, glycerol hyperhydration may be a logistically preferred method due to concomitant decrease in urine output and free-water clearance, which may give a performance advantage by offsetting dehydration. Future research should focus on maintaining plasma glycerol concentrations at levels necessary to maintain osmotic forces required to support continued hyperhydration. Potential benefits of glycerol should be further explored to identify the circumstances or factors that may contribute to an ergogenic effect.

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