A new anti-doping test to detect Growth Hormone misuse in sport
Submitting InstitutionUniversity of Southampton
Unit of AssessmentClinical Medicine
Summary Impact TypeTechnological
Research Subject Area(s)
Medical and Health Sciences: Clinical Sciences, Public Health and Health Services
Summary of the impact
High-profile cases of growth hormone misuse by leading international
sports stars have made the development of an effective detection test a
main priority of global anti-doping organisations. A research team headed
by the University of Southampton developed a new test, adopted at the 2012
Olympic Games, which identified two drugs cheats at the London Paralympic
Games just weeks after it was first introduced. The subsequent bans serve
to act as a powerful deterrent to other athletes and help restore public
confidence in fair competition. The World Anti-Doping Agency has announced
its commitment to rolling out the test internationally.
The development of a test to detect growth hormone (GH) misuse has long
been a major priority of the World Anti-Doping Agency (WADA) to combat
cheating in professional sport. Several high-profile athletes including
Ben Johnson, Marion Jones and Tim Montgomery have admitted taking GH and a
2007 report by former U.S. Senator George Mitchell exposed the scale of GH
misuse in Major League Baseball.
Detecting GH is a significant scientific challenge because, unlike many
substances of abuse, GH is a naturally occurring protein, the
concentration of which varies widely throughout the day. Traditional
antidoping methods are ineffective and although a GH test was introduced
in 2004, it only detects GH up to 24 hours after administration, meaning
users could stop taking it on the eve of the competition without fear of
The GH-2004 team, based at the University of Southampton and led by
Professor Richard Holt (Professor in Diabetes and Endocrinology
2000-current), has developed a method to detect GH misuse up to several
weeks after administration by measuring two GH-sensitive serum markers,
IGF-I and P-III-NP. The method principle was established by Peter Sönksen
(then Professor of Endocrinology, St Thomas's Hospital) who led the
multinational GH-2000 project. When this project ended in 1999, several
issues remained, most notably the possible effects of injury and ethnicity
on test results. The International Olympic Committee requested further
validation to identify "beyond reasonable doubt" GH dopers with minimal
risk of false accusation.
Sönksen joined Southampton as a Visiting Professor (2002-current) and the
GH-2004 project was established by Holt and Sönksen in December 2002 to
address these questions. All clinical studies were undertaken at
Southampton; other Southampton academics included research fellows Dr
Cathy McHugh (2003-2006), Dr Ioulietta Erotokritou-Mulligan (2003-2007)
and Dr Nishan Guha (2007-2011). Laboratory analysis was undertaken at the
WADA-accredited Drug Control Centre at King's College London and
statistical analysis at the Universities of Southampton and Kent. The team
has disseminated its research findings. The project was funded by $2.7m in
WADA grants from 2003 to 2012 and $1m from the US Anti-Doping Agency
The GH-2004 team found small variations in IGF-I and P-III-NP
concentrations with ethnicity but these had no effect on the test
performance (2003-05) [3.2, 3.3], and they found no significant
ethnic effects on peak or maximal responses of IGF-I and P-III-NP to the
recombinant human growth hormone (2004-07) [3.3]. While injury
increases P-III-NP concentration, it does not significantly affect the
test performance (2004-06) [3.1]. The team determined how
adolescence affects marker concentration (2006-08) [3.6] and found
no significant biological variation of marker concentration within
athletes. The team validated the test in two independent data sets [3.4,
3.5] (2005, 2012).
Further studies focused on the practical implementation of the test. The
GH-2004 team determined the optimal pre-analytical collection and storage
conditions (2006, 2011), determined the definitive decision limits for use
by anti-doping laboratories (2010-11), coordinated a successful test pilot
in the London and Rome WADA-accredited laboratories (2011) and wrote the
approved WADA technical manual for implementing the test (2011) ahead of
its first use at the London 2012 Olympics.
References to the research
3.1 Erotokritou-Mulligan I, Bassett EE, Bartlett C, Cowan D,
McHugh C, Seah R, Curtis B, Wells V, Harrison K, Sönksen PH, Holt RI;
GH-2004 Group. The effect of sports injury on insulin-like growth factor-I
and type 3 procollagen: implications for detection of growth hormone abuse
in athletes. J Clin Endocrinol Metab. 2008;93:2760-3.
3.2 Erotokritou-Mulligan I, Bassett EE, Cowan DA, Bartlett C,
McHugh C, Sönksen PH, Holt RI; GH-2004 group. Influence of ethnicity on
IGF-I and procollagen III peptide (P-III-P) in elite athletes and its
effect on the ability to detect GH abuse. Clin Endocrinol (Oxf).
3.3 Holt RI, Erotokritou-Mulligan I, McHugh C, Bassett EE,
Bartlett C, Fityan A, Bacon JL, Cowan DA, Sönksen PH. The GH-2004 project:
the response of IGF1 and type III pro-collagen to the administration of
exogenous GH in non-Caucasian amateur athletes. Eur J Endocrinol.
2010 Jul;163(1):45-54. Epub 2010 Apr 26
3.4 Erotokritou-Mulligan I, Guha N, Stow M, Bassett EE, Bartlett
C, Cowan DA, Sönksen PH, Holt RI. (2012) The development of decision
limits for the implementation of the GH-2000 detection methodology using
current commercial insulin-like growth factor-I and amino-terminal
pro-peptide of type III collagen assays. Growth Horm IGF Res.
3.5 Erotokritou-Mulligan I, Bassett EE, Kniess A, Sönksen PH, Holt
RI. Validation of the growth hormone (GH)-dependent marker method of
detecting GH abuse in sport through the use of independent data sets. Growth
Horm IGF Res. 2007;17:416-23.
3.6 Guha N, Erotokritou-Mulligan I, Burford C, Strobridge G, Brigg
J, Drake T, Bassett EE, Cowan
D, Bartlett C, Sönksen PH, Holt RI. Serum insulin-like growth factor-I
and pro-collagen type III N-terminal peptide in adolescent elite athletes: implications
for the detection of growth hormone abuse in sport. J Clin
Endocrinol Metab. 2010 Jun;95(6):2969-76. Epub 2010 Apr 21.
|US Anti-doping Agency
||Jan 03 – July 05
The development of a methodology for detecting abuse with growth hormone
in sport: GH-2004. Pilot study on ethnic effects 2 ½ years RIG Holt, PH
|World Anti-Doping Agency grants
||Mar 03 – Dec 12
The development of a methodology for detecting abuse with growth hormone
and IGF-I in sport: GH-2004. Pilot study on ethnic effects RIG Holt, PH
Sonksen, EE Bassett, DA Cowan, N Guha
|Partnership for Clean Competition
||Mar 11 – Dec 13
GH-2004: Novel biomarkers for the detection of IGF-I abuse. RIG Holt, PH
Sonksen, EE Bassett, DA Cowan, N Guha, I Erotokritou-Mulligan. *Further
funding up to $200,000 has been agreed subject to results in phases II of
Details of the impact
Research led by the University of Southampton resulted in the
implementation of a more effective test, backed by international
anti-doping organisations, to detect GH misuse. The test had an immediate
impact. During its first use, at the 2012 London Olympic and Paralympic
Games [5.1], the International Paralympic Committee announced
two-year suspensions for two Russian powerlifters found guilty of GH
misuse after returning a positive test [5.2, 5.3].
The effectiveness of GH-2004's new test was demonstrated almost
immediately as neither of these athletes failed the previously available
WADA test for GH misuse; this was introduced in 2004 and has a much
shorter window of opportunity of ~12 to 24 hours making in-competition
detection of GH misuse difficult.
The successful development of a test for GH has been a major goal for the
International Olympic Committee, WADA and national anti-doping agencies
for more than a decade in order to preserve the integrity of and restore
public confidence in professional sport. WADA President John Fahey said:
"We are confident that (the new test) will prove a significant tool in the
fight against doping in sport. It will complement the test that has been
in use since the 2004 Athens Olympic Games, the major difference being
that the anti-doping community now has a much longer detection window to
work with." [5.4].
Although exact numbers are confidential, a significant proportion of
athletes at the London Games were tested for GH misuse using the
Southampton-led test. The implementation of the test will not only lead to
better detection of athletes who are taking GH but crucially act as a
strong deterrent to other athletes considering taking
News of the suspension of the Russian powerlifters through the new
testing procedure generated significant global media interest, leading to
more than 500 online articles [5.5, 5.6]. As well as acting as a
deterrent, this blanket coverage serves to demonstrate to the
sports-viewing public that cheating athletes are being punished and
reassures clean athletes that cheats are not at an unfair advantage.
Andy Parkinson, UK Anti-Doping Agency (UKAD) Chief Executive, said:
"Continual improvement in testing science is fundamental to the global
anti-doping movement, ensuring that sophisticated dopers are caught and
those at a tipping point are deterred. I am delighted that this UK
developed test ... was used at the 2012 Paralympic Games to such good
effect." [5.3]. As Parkinson alludes to in his statement, another
beneficiary of the research is UK science as a whole. The test, created
and refined in the UK, is set to be used around the world.
The successful implementation of the GH-2004 test followed years of close
collaboration between Holt's team and international authorities during the
impact period. WADA, USADA and UKAD held two-day annual meetings with the
academics to review the science. From 2008, Holt established a close
working relationship with UK Sport and UKAD through meetings five times a
year. A statement from UK Sport said: "Any gap in our testing armoury
obviously concerns us as it damages our ability to tackle doping in sport.
As such, to be actively involved in a research project in partnership with
the GH-2004 team at Southampton University and the WADA-accredited
laboratory at King's College ... is of real importance and invaluable in
continuing the drive to combat doping in sport." [5.7].
Holt has been proactive in disseminating the results. From 2003 and
continuing throughout the REF period, he has spoken to a vast range of
media outlets about the GH test, including BBC Radio, newspapers and
television (e.g. the Richard & Judy Show on Channel 4). He has given
lectures at events that have included the 2008 Major League Baseball GH
Summit, Los Angeles (reported by the Los Angeles Times [5.8]
and USA Today [5.9] quoting Holt) and the joint USADA and UK
Sport anti-doping science symposium, London (2011).
At present WADA undertakes ~5000 tests for GH per annum but this is
likely to increase with the introduction of a more effective test. WADA's
goal is to roll out the test internationally and laboratories worldwide
will apply for approval to administer the test. The test is not confined
to athletics. After discussions with Holt, the U.S. National Football
League [5.10] and Major Baseball League made internal
recommendations to commission anti-doping labs in the U.S. to carry out
the test. The test has already been used outside the Olympics in other UK
sports although the details remain confidential. WADA intends to include
the test in athletes' biological passports, which will ensure GH detection
is even more effective.
Sources to corroborate the impact
5.1 David Howman, director general of the World Anti-Doping
Agency, announces the introduction of the test at the London Olympic
Games. This story was picked up by many news agencies including the BBC.
London 2012: Selsouli to miss Games after failed drugs test. http://www.bbc.co.uk/sport/0/olympics/18985217.
Published 25 July 2012. Accessed 6 June 2013.
5.2 Report of suspension of Nikolay Marfin and Vadim Rakitin by
International Paralympic Committee following their positive test at the
London Paralympic Games. Latest Testing Methods Result in Suspension of
Two Russian Powerlifters for Anti-Doping http://www.paralympic.org/press-release/latest-testing-methods-result-suspension-two-russian-powerlifters-anti-doping. Published 8 Sept 2012. Accessed 6 June
5.3 Report of suspension of Nikolay Marfin and Vadim Rakitin by
International Paralympic Committee by UK Anti-Doping including quote by
Andy Pakinson, UK Anti-Doping Agency (UKAD) Chief Executive. UK research
leads to new Growth Hormone test and positive findings. http://www.ukad.org.uk/news/article/uk-research-leads-to-new-growth-hormone-test.
Published 19 Sept 2012. Accessed 6 June 2013.
5.4 Reported on the European Commission website. New test to catch
illegal drug doping in sports including quote by WADA President John
Published 8 October 2012. Accessed 6 June 2013.
5.5 Example of media coverage of the positive GH test at the
Paralympics. New test detects longer-term growth hormone abuse. http://www.topnews.in/healthcare/content/22939new-test-detects-longer-term-growth-hormone-abuse. Published 17 September
2012. Accessed 6 June 2013.
5.6 Example of media coverage of the positive GH test at the
Paralympics. University of Southampton develops better test for banned
human growth hormone.
Published 17 September 2012. Accessed 6 June 2013.
5.7 The UK
Sport perspective on detecting growth hormone abuse. Stow MR, Wojek
N, Marshall J. Growth Horm IGF Res. 2009 Aug;19(4):375-7
5.8 Report of GH summit in Los Angeles. Researchers cite progress
Published 11 November 2008. Accessed 6 June 2013.
5.9 Report of GH summit in Los Angeles. MLB won't be testing for
HGH any time soon.
Published 11 November 2008. Accessed 6 June 2013.
5.10 Evidence of NFL commitment to testing for GH. NFL wants its
players tested for human growth hormone. http://www.nfl.com/news/story/09000d5d81ef2988/article/nfl-wants-its-players-tested-for-human-growth-hormone. Published 25 November 2011.
Accessed 6 June 2013.