There are reports that exogenous recombinant human IGF-I (rhIGF-I) is already being misused by athletes either alone or in combination with GH.
IGF-I has been available for research for many years and more recently a combination of rhIGF I and rhIGFBP-3 has been developed by Insmed. This combination of IGF-I with its binding protein is better tolerated as it is less likely to cause hypoglycaemia or jaw pain.
The US Federal Drug Administration approved the use of IGF-I in a number of clinical settings, such as GH insensitivity syndrome in 2005. The availability of IGF-I has increased since then and with increased availability it is likely that misuse by athletes will increase. Like GH, it use is banned under the International Olympic Committee (IOC) and World Anti-Doping Agency (WADA) list of prohibited substances.
Free IGF-I is available but is associated with the significant side effects of hypoglycaemia and jaw pain. The combination with IGFBP3 is known to reduce the risk of hypoglycaemia.
The detection of exogenously administered rhIGF-I poses a formidable challenge, as it is identical to the endogenously produced hormone. The methods for detecting the misuse of androgenic anabolic steroids and related substances measured by mass spectroscopy are highly sophisticated but such methods are still under development for the testing for misuse with peptide and glycoprotein hormones such as IGF-I. Immuno-assays and blood sampling are currently required for the detection of these substances and, because they are rapidly degraded in the body, urine analyses are not an option.
We recruited 56 volunteers aged between 18 and 35 years who exercised regularly, to take part in the study. In addition to developing the doping test we investigated the reasons why athletes may wish to misuse IGF-I by studying its effects on these healthy volunteers. Baseline assessments were performed at our physiology laboratory in the Southampton Wellcome Trust Clinical Research Facility. These included investigations of body composition using skin fold measurements and dual energy X-ray absorptiometry (DEXA) scanning. The volunteers also performed a treadmill test to assess their physical fitness.
The growth hormone-dependent markers IGF-I and P-III-NP were measured at baseline and volunteers were then randomly assigned to receive either IGF-I or placebo injections. The participants self-administered treatment for 28 days and then the baseline assessments were repeated. The biomarkers were monitored throughout the treatment period and for 8 weeks after the completion of treatment. The blood results are being used to construct formulae to discriminate between those who have taken IGF-I from those in the placebo group. We hope that this project will lead to the creation of a doping test for IGF-I misuse.
The initial results of the double blind study have been published in the Journal of Clinical Endocrinology and Metabolism (3) and Drugs Testing and Analysis (1).
(1) Guha N, Erotokritou-Mulligan I, Nevitt SP, Francis M, Bartlett C, Cowan DA, Bassett EE, Sonksen PH, Holt RI. Biochemical markers of recombinant human insulin-like growth factor-I (rhIGF-I)/rhIGF binding protein-3 (rhIGFBP-3) misuse in athletes. Drug Test Anal 2013 November;5(11-12):843-9.