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AE Nelson is the
Scientific Project
Manager of the
Australia–Japan
Growth Hormone
Doping Project and
KKY Ho is Head
of the Pituitary
Research Unit, Garvan
Institute of Medical
Research and Head
of the Department
of Endocrinology, St
Vincent’s Hospital,
Sydney, Australia.
Correspondence
*Pituitary Research Unit
Garvan Institute of Medical
Research
384 Victoria Street
Darlinghurst
Sydney
New South Wales 2010
Australia
k.ho@garvan.org.au
Received 5 September 2006
Accepted 17 November 2006
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doi:10.1038/ncpendmet0429
198 NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM
Abuse of growth hormone by athletes
Anne E Nelson and Ken KY Ho*
Growth hormone (GH) use was banned in
competitive sport by the World Anti-Doping
Agency because such use presents health risks
to the athlete and violates the spirit of sport.
Despite this ban, anecdotal evidence exists that
GH abuse is widespread. A Google search shows
3.0 million hits for ‘human growth hormone’ of
which approximately 1.2 million are for ‘human
growth hormone supply’. The perceived benefits
of GH abuse are broadly related to the known
anabolic actions of GH and its effects on carbo-
hydrate and fat metabolism; nevertheless, the
efficacy of GH in the enhancement of athletic
performance is largely unproven and long-term
abuse is not without risk.
Administration of GH to adults with GH defi-
ciency has demonstrated benefits; however, the
balance of evidence is weak for any beneficial
effect of GH on strength and fitness in young
healthy adults.1 Although GH induces a measur-
able protein anabolic effect in healthy adults,2
double-blind, placebo-controlled studies in
trained adult athletes have not demonstrated
that GH enhances either muscle strength
or performance.1 The adverse effects of GH
excess—the extent of which is dose-related and
duration-related—arise from its actions on
metabolic processes and tissue growth.3,4 GH
excess causes insulin resistance and increases the
risk of diabetes in susceptible individuals. GH
also has potent antinatriuretic properties that
cause fluid retention, which in turn might result
in edema, carpal tunnel syndrome, arthralgia,
myalgia, or pseudotumor cerebri.4 The human
disease acromegaly suggests that long-term
abuse of GH could result in facial disfigure-
ment, sleep apnea, hypertension, osteoarthritis,
cardiomyopathy, and a possible increased risk
of malignancy. Ironically, muscle structure and
function become impaired in patients with
acromegaly after many years of exposure to
excess GH.1 Of additional concern is the indirect
adverse effects of GH abuse, which include hepa-
titis or HIV contracted from shared needles,
and transmission of prion diseases (such as
Creutzfeldt–Jakob disease) from cadaver tissue,
which is still a source of illicit GH.
The pressure to excel in sport is immense.
In a frequently cited survey by Bamberger and
Yeager (reviewed elsewhere5), over 50% of the
elite athletes questioned said they would take a
performance-enhancing substance if they could
guarantee they won every competition for the
next 5 years and would not get caught, even
if they would die from its adverse effects. The
abuse of GH can start at a young age—surveys
have reported abuse by 5% of 10th grade boys
and by 3.5% of college athletes in the US.5 Doses
of GH used by athletes are estimated at 3–8 mg
daily for 3–4 days each week,3 which results in
an average daily dose of 1–2 mg—approximately
two to three times the daily endogenous GH
secretion by the pituitary gland.
There is strong evidence that ‘polypharmacy’
is widely practiced, in which GH is abused
concurrently with other agents. For example, a
web-based survey reported that 25% of anabolic
androgen steroid (AAS) abusers also took 1–
10 mg GH daily.6 Consideration of the long-term
health risks of GH abuse must, therefore, also take
into account the concurrent use of other doping
agents. AAS abuse may have adverse effects on
the cardiovascular system and mental health,
and is possibly associated with an increased risk
of neoplasia. Many of the adverse effects of GH
abuse are synergistic with those of AAS abuse,
which potentially enhances their overall severity.
GH and testosterone exert independent anti-
natriuretic actions that in combination exacer-
bate fluid retention. Direct effects of AAS abuse
on the myocardia of power athletes have been
reported and are potentiated by concomitant GH
abuse. In addition, case reports in body builders
have described adverse effects of concomitant
GH and AAS abuse that include bilateral median
neuropathy, multiple entrapment neuropathy,
and cardiomyopathy. An increased incidence
of premature mortality that has been reported
among power lifters has also been attributed to
AAS and concomitant GH abuse.
MARCH 2007 VOL 3 NO 3

Tests to detect the presence of exogenous GH
have been developed that should deter GH abuse
in sport. One approach exploits the fact that
the pituitary gland produces several different
isoforms of GH. Administration of recombinant
GH (a single isoform of 22 kDa) suppresses serum
concentrations of the endogenous GH isoforms
and alters their ratio to predominantly reflect the
22 kDa isoform.7,8 These differences can be distin-
guished by specific immunoassays. This method
was implemented by the World Anti-Doping
Agency for the Athens Olympics in 2004. As GH
is usually taken by athletes in the off-season, this
test is expected to be most effective when used in
an out-of-competition setting without advance
notice. A second approach to test for the presence
of exogenous GH measures serum levels of GH-
responsive proteins, such as insulin-like growth
factor 1 (IGF1) and components of collagen turn-
over (e.g. procollagen III). Studies from the GH-
2000 group9 have shown the potential of these
GH-responsive proteins as sensitive markers of
exogenous GH administration, in particular IGF1
and procollagen III propeptide. We have demon-
strated that in elite athletes age is the main demo-
graphic factor responsible for variation in IGF1
and collagen marker levels, whereas the effect of
ethnicity is minor.10 The GH-responsive markers
approach should, therefore, complement the
GH-isoforms approach and extend the window
of detection after GH administration ceases.
We are currently examining the changes in GH-
responsive markers when testosterone is admin-
istered concurrently with GH, as well as inves-
tigating gene expression profiling of peripheral
blood cells to develop a novel GH detection test.
Athletes who use prohibited drugs risk serious
penalties, and medical practitioners who treat
athletes need to be aware of the banned drugs
on the World Anti-Doping Code Prohibited
List and of the athlete’s liability should they
test positive for banned substances. Medical
MARCH 2007 VOL 3 NO 3
VIEWPOINT
www.nature.com/clinicalpractice/endmet
practitioners themselves can be found guilty Competing interests
of doping violations if they traffic, prescribe, The authors declared
they have no competing
or otherwise assist athletes to take banned interests.
substances. Beyond potential involvement in
a doping violation, however, there exists the
basic duty of care of a medical practitioner.
Consideration should be given to warning
athletes of the risks and possible consequences
of GH abuse, and thought must be given
by pediatricians to the possibility of drug abuse
by young athletes. In conclusion, clinicians
need to be aware of drug abuse in sport (even
among their young patients), and be willing to
act as a person of trust who can openly discuss
the uncertain performance benefits as well as
the adverse effects of doping.
References
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growth hormone: a case of the emperor’s new clothes?
Br J Sports Med 37: 100–105
2 Healy ML et al. (2003) High dose growth hormone
exerts an anabolic effect at rest and during exercise in
endurance-trained athletes. J Clin Endocrinol Metab
88: 5221–5226
3 Saugy M et al. (2006) Human growth hormone doping
in sport. Br J Sports Med 40 (Suppl 1): S35–S39
4 Ho KK (1995) The complications of growth hormone
therapy. In Growth Hormone in Critical Illness—
research and Clinical Studies, 225–246 (Ed Torosian
MH) Austin: RG Landes Company
5 Calfee R and Fadale P (2006) Popular ergogenic drugs
and supplements in young athletes. Pediatrics 117:
e577–e589
6 Parkinson AB and Evans NA (2006) Anabolic
androgenic steroids: a survey of 500 users. Med Sci
Sports Exerc 38: 644–651
7 Wu Z et al. (1999) Detection of doping with human
growth hormone. Lancet 353: 895
8 Leung KC et al. (2002) Physiological and
pharmacological regulation of 20-kDa growth hormone.
Am J Physiol Endocrinol Metab 283: E836–E843
9 Longobardi S et al. (2000) Growth hormone (GH)
effects on bone and collagen turnover in healthy adults
and its potential as a marker of GH abuse in sports: a
double blind, placebo-controlled study. The GH-2000
Study Group. J Clin Endocrinol Metab 85: 1505–1512
10 Nelson AE et al. (2006) Influence of demographic
factors and sport type on growth hormone-responsive
markers in elite athletes. J Clin Endocrinol Metab 91:
4424–4432
NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM 199