Glucocorticoids in elite sport: current status, controversies and

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VernecA, etal. Br J Sports Med 2020;54:8–12. doi:10.1136/bjsports-2018-100196

Glucocorticoids in elite sport: current status,

controversies and innovative management

strategies—a narrativereview

Alan Vernec ,

Andrew Slack,

Peter Rex Harcourt,

Richard Budgett,

Martine Duclos

Audrey Kinahan,

Katja Mjøsund,

Christian J Strasburger

Review

To cite: VernecA,

SlackA, HarcourtPR,

etal. Br J Sports Med

2020;54:8–12.

Department of Science and

Medicine, WADA, Montreal,

Quebec, Canada

Medical Affairs, Exactis

Innovation, Montreal, Quebec,

Canada

Department of Integrity,

Australian Rules Football

League (AFL), Melbourne,

Victoria, Australia

IOC, Lausanne, Switzerland

Department of Sport Medicine

and Functional Explorations,

University Hospital (CHU), G.

Montpied Hospital, Clermont-

Ferrand, France

Eirpharm, Ennis, Ireland

Paavo Nurmi Centre, Turun

Yliopisto, Turku, Finland

Endocrinology, Diabetes and

Nutritional Medicine, Charite

Universitatsmedizin Berlin,

Berlin, Germany

Correspondence to

Dr Alan Vernec,WADA,

Montreal, Canada;

Alan. Vernec@ wada- ama. org

Accepted 25 June 2019

Published Online First

20July2019

employer(s)) 2020. Re- use

permitted under CC BY- NC. No

commercial re- use. See rights

and permissions. Published

by BMJ.

ABSTRACT

The use of systemic glucocorticoids (GCs), as well

as local injections, continues to be a controversial

issue in the sport/anti- doping community. There is

widespread and legitimate use of GCs for numerous

health conditions, yet there are concerns about

side effects and the possibility of enhanced athletic

performance in limited settings. This is compounded

by the uncertainty regarding the prevalence of GC

use, mechanisms underlying physiological effects and

complex pharmacokinetics of different formulations.

While WADA continues to promote research in this

complex area, some international sporting federations,

major event organisers and professional sports leagues

have introduced innovative rules such as needle policies,

mandatory rest periods and precompetition guidelines

to promote judicious use of GCs, focusing on athlete

health and supervision of medical personnel. These

complementary sport- speciﬁc rules are helping to ensure

the appropriate use of GCs in athletes where overuse is

a particular concern. Where systemic GCs are medically

necessary, Therapeutic Use Exemptions (TUEs) may be

granted after careful evaluation by TUE Committees

based on speciﬁc and strict criteria. Continued vigilance

and cooperation between physicians, scientists and

anti- doping organisations is essential to ensure that GC

use in sport respects not only principles of fairness and

adherence to the rules but also promotes athlete health

and well- being. The purpose of this narrative review is

to summarise the use and management of GCs in sport

illustrating several innovative programmes by sport

leagues and federations.

INTRODUCTION

The use of systemic glucocorticoids (GCs) in sport

remains a vexing issue. There are some people in

the sport community who view GC treatment as

perfectly acceptable for athletes if clinically indi-

cated, while others believe that athletes with either

chronic or acute medical conditions should be

prevented from competing rather than be allowed

to use systemic GCs or local injections. There are

proponents of removing GCs entirely from the

WADA List of Prohibited Substances (List), while

others want to increase the number of prohibited

routes and not allow Therapeutic Use Exemptions

(TUEs).

Are GCs a scourge in sport or a therapeutic

product that is relatively well controlled? This

paper examines (1) the prevalence of GC use in the

general and athletic populations, (2) anti- doping

regulations, (3) the science around whether

systemic GCs can enhance performance, (4) health

risks, adverse effects and negative effects on perfor-

mance, (5) strategies and policies by sporting feder-

ations to ensure appropriate use of GCs and (6)

current management of the TUE process for GCs.

Prevalence of GC use in the general and athletic

populations

GCs are one of the most widely used and effective

medication classes in the general population and

are available in a variety of pharmaceutical formu-

lations (eg, injections, tablets, creams, eye- drops,

ear drops, inhalers and nasal sprays).

Administered

for both their systemic and local effects, GCs are

used globally in a wide array of clinical specialities,

primarily for their anti- inflammatory and immu-

nosuppressive properties. In some settings, the

medical use of oral GCs appears to have increased

in recent years as GCs are an accessible and afford-

able alternative to targeted but costlier medications.

Prevalence of systemic use predominately for short-

term use varies between 1% and 3%

2 3

although

ranged as high as 17.1% in a recent study of adults

in France.

Oral GCs are commonly used in many

countries as part of first- line treatment in some

infectious disease settings (acute otitis media, phar-

yngitis) although determining efficacy is still an area

of active investigation.

5 6

A large survey of adults in

48 western European centres found that a median

3.5% of respondents were currently using asthma

medications (many of which include inhaled GCs),

with a prevalence of 80% in those experiencing

recent asthma attacks.

The Global Initiative for

Asthma GINA 2018 report recommends early use

of inhaled GCs in asthma management

although

there is no accompanying prevalence data.

In athlete populations, there is an increased prev-

alence of musculoskeletal injuries and asthma

9 10

and therefore frequent legitimate therapeutic GC

use would not be surprising. Nevertheless, there is

a scarcity of prevalence estimates in athlete popu-

lations. An analysis of abbreviated TUEs where the

IOC was notified of GC use by athletes in advance

of Olympic Games in the 1990s and early 2000s

suggests that at least 5% to 12% of competitive

elite athletes were treated with GCs by all routes,

predominantly inhaled .

In a recent unpublished

international survey of medical doctors working

with elite athletes, over 85% reported that they

have at least occasionally administered injectable

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Review

GCs as part of their normal practice (personal communication,

Dr David Hughes, Australian Institute of Sport).

Anti-doping regulations

GCs, administered by certain routes, were first prohibited in

sport by the IOC in 1985 and have been prohibited by WADA

since its initial List, published in 2004. Substances or methods

are considered for inclusion in the List if they meet two out of

the following three criteria as stated in the World Anti- Doping

Code: (1) potential to enhance, or enhances sport performance;

(2) represents an actual or potential health risk to the athlete;

(3) violates the spirit of sport.

GCs are prohibited in- compe-

tition when administered by ‘systemic’ (oral, rectal, intramus-

cular or intravenous) routes.

Administration by all other routes

(including intra- articular and other periarticular injections) is

regarded as local administration and are not prohibited in- com-

petition. GC administration by any route is not prohibited out-

of- competition (OOC).

Regardless of the specific GC substance and their individual

pharmacological characteristics, a presumptive adverse analyt-

ical finding (AAF) is reported by WADA- accredited laborato-

ries when the urinary levels of in- competition samples exceed a

30 ng/mL reporting level. Pharmacokinetics of GCs is complex

and influenced by the formulation, type of esterification and

salt, administration route, site and method of administration.

Accordingly, while the laboratory reporting limit may demon-

strate the presence of a GC, it cannot necessarily indicate if the

administration was in- competition or OOC or likely to have a

pharmacological or ergogenic effect. Any physician or athlete

will be unsure when to stop using systemic GCs before the

in- competition period to avoid exceeding the reporting limit. To

further complicate the pharmacokinetic picture, intra- articular

injections may give rise to systemic levels and physicians may

inadvertently mischaracterise the site of injection in the absence

of radiological or ultrasound guidance. Substance- specific

reporting limit refinements are an area of active discussion and

research among WADA- appointed experts and are beyond the

scope of this paper.

Do systemic GCs enhance performance?

Some athletes have undoubtedly attempted to harness the

purported performance- enhancing effects of systemic GCs that

they perceive to be beneficial in their particular sporting disci-

pline. However, the complex and pleiotropic mechanisms of

GC action suggest that these medications are an unwieldy tool

for the athlete seeking to gain a performance advantage and are

considered to be a less popular component of doping regimens

than in the past.

Some patients and athletes reported experi-

encing euphoria following systemic administration.

However,

the scientific evidence supporting measurable euphoria in clin-

ical populations is equivocal and the interpretation of the data is

complicated by the association of confounding chronic pain.

16 17

There is no evidence of performance- enhancing effects from

short- term use of systemic GCs.

18–22

There are randomised

double- blind cross- over studies which suggest that athletes can

exploit high- dose week- long courses of oral GCs to improve their

submaximal intensity exercise performance for brief periods of

time.

23 24

These dosages would be easily detected during anti-

doping tests, if taken in- competition. The precise mechanism

for this effect is unclear but suggested to result from a combi-

nation of effects on metabolism, muscle, inflammation and the

nervous system. This drug effect was shown in one study of male

athletes whose training was tightly periodised alongside oral GC

use.

Exploiting this type of performance- enhancing regimen

while effectively avoiding adrenal insufficiency and detection by

standard in- competition doping controls would require meticu-

lous medical supervision. It may also require more complex and

exotic pharmacological manipulation of the hypothalamic–pitu-

itary–adrenal axis than that offered by prescription GCs.

Athletes and doctors have described inappropriate methods

whereby systemic GC use, restricted nutrition and low- intensity

training might be combined OOC to lose weight and preserve

muscle mass.

However, given the widely understood protein-

catabolic functions of GCs,

27 28

this doping mechanism remains

speculative and controversial. Furthermore, efficacy may be

dependent on the use of GCs as part of a complex cocktail that

includes other prohibited but poorly detected hormones such as

insulin.

Recent accounts of systemic GC’s supposed potency have

come from athletes who have also confessed to concurrent use of

other performance- enhancing methods and substances, including

anabolic agents such as testosterone.

14 30 31

Such GC regimens

may only have relevance in a small subset of sporting disciplines,

such as in the steep mountain stages of cycling’s Grand Tours,

where athletes might be willing to accept compromise in their

training regimens or absolute power output in the pursuit of a

superior power to weight ratio. OOC use would still necessi-

tate a prolonged continuation of GC use into the competition

period to avoid adrenal insufficiency due to feedback mecha-

nisms. Prolonged GC use carries well- known medical risks, some

of which could permanently diminish athletic performance.

Health risks, adverse events and negative effects on

performance

Treatment with GCs for many conditions has a long history

and a reasonable safety profile. High doses or chronic use of

systemic GCs pose some risk to the health of the athlete. Careful

examination, diagnosis and deliberation by the physician is

paramount and the benefits of treatment need to be weighed

against potential risks and adverse effects. Potential performance

enhancement use, described above and thought to be restricted

to specific sport contexts with high- dose GC use, is also poten-

tially associated with significant risks to the health of an athlete.

Adverse events with well- established causal associations to

clinically appropriate GC use touch on virtually every human

system, range from acute to chronic negative health outcomes

and include adrenal insufficiency, immunodeficiency, osteopo-

rosis, muscle wasting, tendon/fascia failure, avascular necrosis

of the femoral head, various electrolyte, nutrient and other

metabolic imbalances, glaucoma and cataracts. Perhaps because

GCs are such common and clinically versatile medications, some

physicians may overestimate their therapeutic value and under-

estimate the severity of associated adverse events.

33 34

Even a

single intra- articular injection could result in clinically signifi-

cant adrenal insufficiency leading to malaise, electrolyte imbal-

ance and immunosuppression for several weeks.

35–37

Importantly, the aetiology of these symptoms may be unrec-

ognised by the athlete and medical personnel, particularly in a

sporting context where athletes train at high intensity and symp-

toms can masquerade as fatigue related to overtraining. Further-

more, an athlete who suffers trauma or serious injury may be at

increased risk for adrenal crisis due to the hypothalamic–pitu-

itary–adrenal suppression from prior GC use. This could be

particularly problematic if the athlete fails to disclose this prior

use.

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Table 1 League sport recommendations for precompetition glucocorticoid use

Route Oral and rectal Intramuscular, intravenous

Intra- articular, intrabursal, periarticular and other ‘local’ tissue

injections

Recommendation Only under medical control;

cease 1 week precompetition

Avoid altogether; consider requesting a TUE if

use is less than 1 month precompetition

Avoid 3 days precompetition;

avoid long- acting formulations (triamcinolone);

follow manufacturer’s dose recommendations;

retain full medical documentation for AAF investigation purposes

AAF, adverse analytical ﬁnding; TUE, Therapeutic Use Exemption.

Both the efficacy and potential harm of intra- articular injec-

tions are highly debated. Evidence from a recent prospective

sham- controlled study in patients with osteoarthritis suggested

that frequent triamcinolone knee injections, delivered according

to a predetermined schedule, failed to effectively manage long-

term pain and led to a statistically significant reduction in cartilage

thickness.

Nevertheless, medical society recommendations, as

well as a comprehensive meta- analysis support the efficacy and

safety of the very same intervention,

39 40

strongly suggesting that

judicious use of intra- articular injections in appropriate patients

and circumstances can yield positive outcomes. There is a lack of

published evidence on safety or harm of intra- articular GC use

in athletic populations, and further research is urgently required

due to the ubiquitous use of intra- articular GCs.

Policies to ensure the appropriate use of GCs

Despite concerns of possible abuse for a competitive advantage

or potential detrimental effects on athlete health, GCs are widely

used in sport for legitimate therapeutic reasons. Understanding

that the List is harmonised across all sports from Archery to

Wakeboarding, doping with GCs is not a concern where the

purported benefits of high- dose GC use (prolonged power

output at submaximal exercise intensities or aggressive catabolic

weight management) are unlikely to be performance enhancing.

Therefore, an AAF for GC would not likely be associated with

any doping intent. The use of systemic GCs in many sports must

be considered in a different light than in high- risk sports such as

cycling, where abuse is well- documented and scientific evidence

provides some support.

Mindful of the specific challenges posed by GC use in sport,

sporting and anti- doping organisations have introduced innova-

tive policies and are strengthening existing regulations to address

the reasonable therapeutic use of GCs.

Needle policies

In cycling, there have been years of anecdotal stories concerning

GC abuse and its use as a doping agent. Interestingly, many of

these athletes neglected to mention the multiple other potent

anabolic and erythropoietic doping agents that they were using

concurrently.

31 41

Historically, the number of AAFs and athlete

testimonies have supported the assertion of widespread abuse

of GCs in cycling, although there is evidence to suggest that

its abuse has declined in recent years. Nevertheless, the Union

Cycliste Internationale (UCI) enacted revisions to its medical

rules in 2011 prohibiting the use of needles 48 hours prior to

competition, for any purpose, unless strict medical criteria were

met. This was modified in 2013 requiring 8 days rest prior to

competition following any GC injection.

The response of

doctors to these rule changes has been mainly positive because

they help obviate pressure from athletes and team personnel to

administer injections. The intent was also to protect athletes’

health, obliging them to rest and recover properly. According

to the UCI’s own statistics, these rule changes effectively

prohibiting all GC injections in- competition have further helped

to reduce the occurrence of GC AAFs. Since the reporting values

were established at 30 ng/mL, the number of AAFs in- competi-

tion declined steadily from 72 per year in 2005 down to 9 AAFs

in 2016 (personal communication, Francesca Rossi, Director,

Cycling Anti- Doping Foundation). The UCI’s use of distinct and

specific rules to support the List and World Anti- Doping Code

and to address abuse problems that have disproportionately

affected cycling appears to be effective.

The IOC has also adopted a needle policy for all participating

athletes at the Olympic Games.

Needles must not be used

except by: (1) medically qualified practitioners for the clinically

justified treatment of injury, illness or other medical conditions

or (2) those requiring autoinjection therapy for an established

medical condition with a valid TUE, for example, insulin treat-

ment for diabetes. This policy helps the IOC identify potential

abuse of GC injections and focus on identifying and regulating

physicians who may be engaged in aberrant medical practice,

rather than sanctioning athletes who are following their doctor’s

advice. This needle policy has been implemented by several

International Sport Federations to strengthen controls on the use

of substance injections, including GC injections.

Needle policies are constructive approaches to curbing abuse

of potentially dangerous or unnecessary GC injection practices

that neither stigmatise nor penalise athletes and responsible

physicians. Each sport should decide whether a needle policy is

warranted to control potential abuse.

League GC policies

Australian Football League (AFL) athletes, like many profes-

sional athletes, face strenuous and often short careers marked

by multiple injuries and significant load management issues

resulting in wear and stress on joints. The judicious use of GC

is not infrequently part of an overall therapeutic strategy. When

considering whether GCs may confer deliberate or inadvertent

performance advantages, data collected in the AFL provide an

illuminating context. A review of doping control forms and

mandated documentation of all injections collected over an

8- month period from over 800 athletes found that 25% of

athletes received a local (usually intra- articular) injection during

the season. Of those who received injections, the average number

received during the season was 2.2 injections. Further analysis

revealed that use of GC injections actually declined during the

finals period, supporting a pattern of clinically driven use consis-

tent with injury management rather than one of abuse (personal

communication, Dr Peter Harcourt, AFL Medical Director).

While not without risk, intra- articular GC injections carried out

judiciously do not contravene principles of good medical prac-

tice. All GC use in the AFL is annually reviewed and forms part

of the league’s medical auditing of team medical personnel using

a peer review format. When GC use exceeds the recommenda-

tions, the league authorities act to ensure athlete welfare (see

table 1).

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Figure 1 The percentage of TUEs that were entered in the WADA’s

ADAMS database prospectively and retroactively. It also compares

TUEs for all substances with glucocorticoids only. ADAMS, Anti- Doping

Administration and Management System; TUEs, Therapeutic Use

Exemptions.

Figure 2 The duration of granted GC TUEs from the ADAMS database for the period 2012–2016. ADAMS, Anti- Doping Administration and

Management System; GC, glucocorticoid; TUEs, Therapeutic Use Exemptions.

With good administration systems, professional sports are

able to implement regulatory controls similar to the successful

‘needle’ and ‘athlete health’ policies of the IOC, UCI and a

number of other international sport federations. Physician

control is easier in the setting of team sports, particularly with

professional teams where there are contracted team physicians

and auditing of healthcare practices.

TUEs: a critical part of GC regulation

Athletes subject to doping control who are legitimately treated

with prohibited routes of GCs in or very near to sporting

competition may be permitted to use the medication if granted

a TUE. However to avoid abuse, specific and strictly enforced

rules are described in the International Standard for TUEs

(ISTUE) and the World Anti- Doping Code for athletes seeking

a TUE.

12 44

ISTUE Article 4.1 lays out four strict criteria, all

of which must be met in the estimation of a TUE Committee

(TUEC) composed of physicians with expertise in the areas of

medicine relevant to the application. Contrary to occasional

reports in the media of rampant TUE abuse, TUEs are seldom

sought by elite athletes.

The number of TUEs in the last

four Olympic Games has remained steady at approximately

1.2% (WADA data, confirmed by the IOC). Importantly, when

granted, a TUE for a GC directly relates to individual medical

needs and generally is narrowly limited in dose, frequency and

duration of use. Anecdotal stories of cheating with GC TUEs

are mostly reported in cycling and have been less common in

the last 5 years. This may be due to a better understanding by

athletes of the medication’s benefit–risk relationship, the more

stringent application of the rules and investigative follow- up

of AAFs.

Due to the value of systemic GCs in the treatment of many

medical conditions common in athletes (eg, exacerbations of

asthma, sinusitis, musculoskeletal injuries, acute allergic reac-

tions and inflammatory bowel disease (IBD)), this class of

prohibited substances consistently makes up the largest share

of granted TUEs, according to recent statistics collected from

WADA’s Anti- Doping Administration and Management System

(ADAMS) database (see figure 1).

A prospective TUE application is preferred both for control

and to provide permission certainty for athletes. However, GC

TUE applications are often requested retroactively (~40%).

This is consistent with clinical practices in the management of

acute situations where elite athletes face challenges of travel

and demanding training schedules. An athlete will tend to

follow their doctor’s advice and accept immediate medical

treatment rather than waiting and applying for a TUE. A retro-

active TUE application scenario can lead to significant anxiety

and uncertainty for clean athletes and their doctors who know

that rejection of a retroactive TUE application may result in

an anti- doping rule violation and significant consequences

for the athlete. Promoting clean sport requires both careful

clinical decision- making and diligent medical documentation.

Consistent with indications typical for athlete populations and

responsible treatment decisions, most GC TUEs registered in

the ADAMS are for a duration of 1 week or less (see figure 2).

TUEs granted for longer durations are more often prospective

and are typically granted for inflammatory arthritis, IBD and

other chronic autoimmune conditions.

TUECs evaluate applications based on the ISTUE and WADA’s

TUE Physician Guidelines. These guidelines, regularly updated

by sport and specialist physicians, address various health condi-

tions, including a number where systemic GCs are considered an

important element of treatment (eg, musculoskeletal conditions,

IBD, adrenal insufficiency and asthma).

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SUMMARY

The use of GCs in sport is a highly complex issue due to their

widespread use in medicine, the many formulations and routes

of administration with varying pharmacokinetics, negative

health effects and potential doping associations. The mecha-

nisms of action and ergogenicity in different sporting disciplines

remain to be fully elucidated. Anti- doping regulations as well as

sport policies monitoring physician behaviour have been imple-

mented to control the use of GCs in sport. Further research is

necessary to continue to refine thresholds as well as monitor

potential abuse and judge the effectiveness of present regulatory

programmes. A careful application of the TUE process will allow

injured or ill athletes the right to compete while maintaining

fairness within sport.

What is already known

► Historically, there has been considerable tension between

anti- doping rules predicated on the evidence of potential for

performance enhancement and the acceptance of the use of

systemic glucocorticoids (GCs) for the treatment of medical

conditions in elite athletes.

► The prevalence of GC use in both the general and athlete

population remains challenging to quantify and mechanisms

of action promoting performance enhancement in sports have

yet to be fully elucidated.

What are the new ﬁndings

► Where GC abuse (or overuse) is a potential concern, some

sport federations, major event organisations and professional

sport leagues have developed rules and recommendations to

govern the use of GC, taking into account current knowledge

of risks and beneﬁts to strike a balance between fair play and

athlete health.

Acknowledgements The authors acknowledge the contribution of David Healy in

the preparation of this manuscript.

Funding The authors have not declared a speciﬁc grant for this research from any

funding agency in the public, commercial or not- for- proﬁt sectors.

Disclaimer Each of the authors conﬁrms that this manuscript has not been

previously published and is not currently under consideration by any other journal.

Neither have the Working Group conclusions and recommendations contained in the

review ever been made public in any previous forum. Additionally, all of the authors

have approved the contents of this paper and have agreed to abide by the British

Journal of Sports Medicine’s submission policies.

Competing interests AV works for the WADA. RB, PH, AK are members of the

WADA List Expert Group and KM is a member of the WADA TUE Expert Group. The

content of this manuscript does not represent any ofﬁcial views of WADA.

Patient consent for publication Not required.

Provenance and peer review Not commissioned; externally peer reviewed.

Open access This is an open access article distributed in accordance with the

Creative Commons Attribution Non Commercial (CC BY- NC 4.0) license, which

permits others to distribute, remix, adapt, build upon this work non- commercially,

and license their derivative works on different terms, provided the original work is

properly cited, appropriate credit is given, any changes made indicated, and the use

is non-

commercial.

See:

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org/

licenses/

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nc/

0/.

ORCID iDs

AlanVernec http://

orcid.

org/

0000-

0002-

7127-

192X

MartineDuclos http://

orcid.

org/

0000-

0002-

7158-

386X

Christian JStrasburger http://

orcid.

org/

0000-

0001-

7905-

7357

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