The human competitive nature is not only innate but essential in evolutionary and survival terms. In the sporting arena, this manifests as an all-consuming drive to win. The enormous financial gains successful sportsmen and -women can accrue and the political imperative for a national side to achieve have led some professional athletes to resort to cheating to win. The use of performance-enhancing substances has become increasingly sophisticated, and there are concerns that the athlete who wins no longer has the best physiology but the best pharmacologist.
Growth hormone (GH)1 was first isolated from the pituitary gland in 1957 (1). By the 1980s, its anabolic actions had been well described, and GH was established as a drug of abuse (2). Detection of the abuse of exogenous GH provides considerable challenges, which are only now being met.
In this review, we will discuss the context in which GH is abused as well as the reasons why. We will also describe the research that has led to methodologies that can now detect GH abuse with high specificity and sensitivity.
Brief History of Doping
Doping is defined in the World Anti-Doping Agency (WADA) code as "the administration of or use by an competing athlete of any substance foreign to the body or any physiological substance taken in abnormal quantity, or taken by an abnormal route of entry into the body with the sole purpose of increasing in an artificial and unfair manner their performance in competition." The use of artificial means to enhance performance dates back to Ancient Greco-Roman times when figs were used to assist performance. The term "doping" comes from the word "dop", which is a substance made from grape skins used by Zulu warriors to enhance battle prowess (3).
The first recorded drug-related fatality occurred in 1886 when Andrew Linton died on the Bordeaux-Paris cycle race, allegedly from an overdose of strychnine, heroin, and a compound known as "trimethyl". In 1967, the International Olympic Committee established a Medical Commission and formulated an official list of prohibited substances.
The first systematic testing began at the 1972 Olympic Games in Munich with the analysis of more than 2000 urine samples by gas chromatography (GC) with nitrogen-selective detection for stimulants. Systematic urinary screening was introduced in 1983 at the Pan American Games, and blood testing was used for the first time in 1994 in the Lillehammer XVII Olympic Winter Games in an attempt to detect blood doping (4).
WADA was established in 1999 and has produced a list of banned substances that have been classified according to their mode of action. An athlete is considered to have violated the regulations if the prohibited substance is discovered in the athlete’s body fluids or if the athlete attempts to use a prohibited substance or method, fails to submit a sample once requested, or fails to make him- or herself available for out-of-competition testing, unless the athlete can demonstrate that the presence of the substance is the result of a physiologic or pathologic condition (5).
The fear of detection and subsequent disgrace and loss of income is a stronger deterrent than the thought of personal harm. In a survey by Sports Illustrated, 195 of 198 athletes said that they would take a performance-enhancing drug if they were guaranteed to win and not be caught; 50% stated that they would still take the substance even if they would die from a side effect of the drug after 5 years of successful competition (6).