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Spirit of Sport – July, 2014

Building on the existing tests for growth hormone (GH) abuse in sport, scientists continue to make advancements in successfully detecting doping in sport. Now, research appearing in Clinical Chemistry, the journal of the American Association of Clinical Chemistry, shows that measuring insulin-like growth factor 1 (IGF-1) as a biomarker of GH activity, through a chemistry technique known as liquid chromatography-tandem mass spectrometry (LC-MS/MS), could increase the ability to detect GH doping and enhance inter-laboratory precision.

A team of researchers from five laboratories in three countries, formed an unprecedented international working group on this topic, led by USADA’s Chief Science Officer, Larry D. Bowers Ph.D. and funded by the Partnership for Clean Competition (PCC). The PCC is a unique research collaborative founded by USADA, the United States Olympic Committee (USOC), Major League Baseball (MLB), and the National Football League (NFL) for the express purpose of supporting the world’s top scientists and innovators in conducting high quality anti-doping research and development, to help generate effective methods and resources for detecting and deterring the use of performance-enhancing substances and methods. The working group, established in 2011 as part of an initiative to develop new tests for GH biomarkers, has demonstrated that using LC-MS/MS instead of antibodies to measure IGF-1 concentrations increases measurement precision. For anti-doping purposes, the LC-MS/MS method has a second significant advantage over immunoassay – as IGF-1 is identified in addition to being quantified. The results may contribute to the development and global adoption of the biomarkers GH test in anti-doping.

Currently, two approaches have been developed for detecting GH in sport applications. The GH isoforms test, reported in Clinical Chemistry in 20091, has been successfully used for a number of years to identify athletes abusing GH; however, it is limited by a short detection window. The biomarkers test, which measures serum concentrations of IGF-1 and another protein produced by the action of GH, has a much longer detection window, potentially up to a number of weeks. The two tests complement each other, and could be used in tandem to greatly enhance the ability to detect prohibited GH use by athletes.

Athletes purportedly abuse GH to obtain its musclebuilding and fat breakdown activity. Some actions of GH are the result of increased IGF-1 concentrations in the blood from the response of the liver to GH stimulation. Anecdotal evidence suggests that IGF-1 abuse may also be on the rise. Side effects of this abuse include diabetes, aggravation of heart disease, and abnormal organ growth, among others.

“Not only are these research results groundbreaking, but the selfless work and cooperation of the members of this working group, with the PCC’s support, demonstrates the power of collaborative research,” said Bowers, USADA Chief Science Officer and PCC Scientific Advisory Board Chair. “Bringing together top scientists and innovators in focused research to identify and resolve analytical problems is critical to advancing anti-doping science.” Additionally, the PCC IGF-1 LC-MS/MS working group’s study demonstrates the benefits of the harmonization of – or ensuring uniformity among – clinical laboratory test results, an important healthcare issue.

“In addition to being an important anti-doping testing advancement, new testing methodology arising from these findings could also aid in the diagnosis and treatment of disorders caused by the natural over- or under-production of GH,” said Andy Hoofnagle, M.D., Ph.D, and an associate professor of Laboratory Medicine and Pathology at the University of Washington and a senior author on the paper.