Original article

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BJSM Online First, published on December 14, 2011 as 10.1136/bjsports-2011-090492
Original article
Monitoring performance, pituitary–adrenal hormones
and mood profiles: how to diagnose non-functional
over-reaching in male elite junior soccer players
Sándor L Schmikli,1 Wouter R de Vries,1 Michel S Brink,2 Frank JG Backx1
Magnus Institute of
Neuroscience, Department
of Rehabilitation, Nursing
Science and Sport, University
Medical Center Utrecht,
Utrecht, The Netherlands
2Center for Human Movement
Sciences, University Medical
Center Groningen, Groningen,
The Netherlands
Correspondence to
Sandor Schmikli, Department
of Rehabilitation, Nursing
Science and Sport, University
Medical Center Utrecht,
Research coordinator Sports
Medicine, Heidelberglaan 100,
3508 GA, The Netherlands;
[email protected]
Received 12 August 2011
Accepted 12 November 2011
Objective To verify if in male elite junior soccer players
a minimum 1-month performance decrease is accompanied by a mood profile and hormone levels typical of
non-functional over-reaching (NFOR).
Design A prospective case-control study using a
monthly performance monitor with a standardised field
test to detect the performance changes. Players with
a performance decrease lasting at least 1 month were
compared with control players without a performance
decrease on mood scores and pre-exercise and postexercise levels of stress hormones.
Setting Sporting field and sports medical laboratory.
Participants Ninety-four young elite soccer players were monitored during the 2006–2008 seasons.
Twenty-one players were invited to the laboratory, seven
of whom showed a significant performance decrease.
Main outcome measures Performance change over
time, scores on the profile of mood states and premaximal and postmaximal exercise serum levels of adrenocorticotropic hormone (ACTH), growth hormone (GH)
and cortisol.
Results Players with a performance decrease showed
psychological and hormonal changes typical of the nonfunctional state of over-reaching. Scores were higher on
depression and anger, whereas the resting GH levels and
ACTH levels after maximal exercise were reduced. ACTH
and GH were capable of classifying all but one player
correctly as either NFOR or control.
Conclusions Performance-related criteria in field tests
are capable of identifying players with worsened mood
and adaptations of the endocrine system that fit the
definition of NFOR. Performance, mood and hormone
levels may therefore be considered as valid instruments
to diagnose NFOR in young elite soccer players.
Over the past 30 years, much attention has been
given to the hormones of the hypothalamus-pituitary axis in studies examining the markers of the
overtraining process. In 1998, Lehman et al1 suggested that the overtraining syndrome (OTS) was
the result of a malfunctioning of the regulatory
processes in the hypothalamus and the pituitary.
However, in 1991, Fry et al2 already mentioned
that in addition to a reduced pituitary response
due to a reduced pituitary sensitivity to hypothalamic stimulation, a decreased sensitivity to adrenocorticotropic hormone (ACTH) at the adrenal
gland could also explain why overtrained athletes
showed reduced levels of cortisol (C) in response
to stress. In fact, in 1985, Barron et al 3 reported
that a pharmacological stress test (insulin-induced
2011. Produced by
SL, de VriesArticle
WR, Brinkauthor
MS, et al. Br
J Sports
(2011). doi:10.1136/bjsports-2011-090492
hypoglycaemia) showed reduced growth hormone
(GH), prolactin and ACTH responses in overtrained athletes. Many other hormones produced
by the pituitary gland have been studied (eg, luteinising hormone, follicle stimulating hormone) in
the subsequent years, but the current consensus is
that no single objective marker can reliably identify the OTS.4–8
The lack of any scientific evidence for diagnostic parameters in OTS is associated with various
methodological issues, the lack of uniform definitions, and as a result an inconsistent use of the
terms over-reaching (OR), overtraining (OT) or
the OTS.4 5 7 9–12 Evidently, this makes any interpretation of the results from previous studies with
subjects anywhere between a compensated and
a decompensated state of adaptation13 to stress
extremely difficult.
A lack of uniformity must have been one of the
arguments to rephrase defi nitions, terms and the
timeframe in the process of overtraining in a position statement8 in 2006, in which the process of
overtraining was divided into three phases. It was
suggested that functional OR (FOR) would last
only days to weeks, the latter being similar with
general OR according to Kreider.10 An underperformance persisting for weeks or months was associated to a transitional state called ‘non-functional
OR’ (NFOR). Longer periods of underperformance
were then linked to the OTS. Until now, only a
small number of studies reported the hormone
levels in NFOR athletes.14–17 Unfortunately, none
of the studies on NFOR provided characteristics
typical to the transition of FOR to NFOR. Either
the studies failed to induce NFOR14 15 or NFOR
was diagnosed retrospectively several months
after the transition took place.16 17 According to
Uusitalo,18 prevention is still the best treatment in
OTS. However, if an unknown process causes any
disease or syndrome, the opportunity to intervene and prevent such a process should be sought
in its earliest stages: when the fi rst signs and
symptoms (SAS) appear. According to the latest
model in OTS,8 such SAS should be associated to
the point that FOR evolves into NFOR. Therefore,
in a prospective case-control study, the aim was
to detect the early markers of NFOR in a group
of young elite soccer players. In accordance with
the Steinacker model,13 it was hypothesised that
ACTH, C and GH responses to (physical) stress
should be reduced in NFOR players, and particularly that reduced C levels would be related to a
reduced adrenal sensitivity to ACTH. Premaximal
and postmaximal exercise levels of these hormones in blood were compared between players
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Original article
showing a persistent reduction in the performance lasting
more than 4 weeks and control players without a performance
reduction. To confi rm the diagnosis of NFOR further, differences in mood (profi le of mood states (POMS)) were also tested
for. Finally, we evaluated the diagnostic qualities of NFOR.
Table 1 Average mood scores* of seven NFOR players and 12
controls prior to maximal exercise testing
6.9 (2.8)
1.3 (0.7)
11.3 (1.1)
3.8 (1.1)
6.6 (1.2)
5.1 (0.8)
12.1 (1.1)
11.5 (0.8)
6.0 (1.8)
3.0 (0.8)
*N=19, 2 control cases missing, SEM in brackets.
†Significant group difference (p<0.05).
NFOR, non-functional over-reaching.
Of the 94 young elite soccer players (mean age 16.5 years, range
15–18 years), 21 players were included for laboratory testing
during the 2006/2007 and 2007/2008 season (seven players
with a performance decrease and 14 controls). Selection for
laboratory testing during a competitive season took place on a
monthly basis using performance changes measured in sportspecific field tests. Young elite soccer players with a persistent
performance decrease lasting at least 1 month, that is, measured at two consecutive field tests, were suspected of NFOR
(hereafter NFOR players). Controls were randomly selected
from the same age group only if they did not show a performance decrease for at least 1 month. Controls were invited
and tested at the laboratory within 7 days after the last performance test. The study was approved by the Dutch Central
Committee on Research Ethics involving Human Subjects
(study no: NL12864.000.06). All participants provided written
informed consent, including both parents if participants were
younger than 18 years of age.
Interval shuttle run test for soccer players
To determine the performance capacity in soccer players,
a submaximal interval shuttle run test (ISRT) was used.19 20
During the entire season, the submaximal intensity was set at
70% of the maximal number of runs achieved at the start of
the season. An elevated heart rate response indicated a state
of over-reaching.21 22 During the outdoor ISRTs, players alternately ran for 30 s and walked for 15 s. The running speed
increased from 10 km/h every 90 s up to 15 km/h depending on the baseline maximal running performance. Heart rate
(in beats/min) was recorded at 5-s intervals (Polar, Kempele,
Finland; Suunto, Vantaa, Finland). The tests were performed
every month at the start of a training session as a substitute
for the warm-up. A reduced physical fitness and a decreased
sports-specific performance over a period of time are the most
prominent indicators of NFOR.8 Therefore, players with an
elevated heart rate response exceeding the day-to-day variance of ≥5 beats/min 23, and a relative heart rate increase of
at least 5% persisting for at least 1 month (and measured at
consecutive field tests) were included as NFOR players.
Laboratory tests
Profile of mood states
A validated short version of the POMS24 25 was used containing 32 items in five subscales: ‘tension’, ‘depression’, ‘anger’,
‘fatigue’ and ‘vigour’. Participants responded on a five-point
Likert scale ranging from 0 (not at all) to 4 (extremely). Mood
profi les were obtained prior to a standardised lunch (about
71% CHO, 19% protein and 10% fat).
at 10 km/h until voluntary exhaustion. The test ended after
1-min recovery running. The heart rate was monitored at 5-s
intervals (Suunto, Vaanta, Finland; Polar, Kempele, Finland).
All exercise tests were supervised by a sports physician.
At least 2 h after the standardised lunch, and within 5 min of
the start of the treadmill test (between 13:00 and 15:00 p.m),
blood samples were taken under resting conditions in supine
position from an antecubital vein in Dickinson vacutainer tubes
(Becton Dickinson, Franklin Lakes, New Jersey, USA). Samples
were taken again in supine position 1 min after recovery walking had ended, mostly within 20 min after the start of the test.
SSTII tubes were used for cortisol and GH and K2E EDTA
tubes for ACTH. Samples were immediately stored on ice and
transported to the laboratory for subsequent analysis. Serum
cortisol was determined by radio immunoassay, whereas
serum GH and ACTH levels were determined using chemiluminescence immunoassay.
Statistical analyses
Statistical analyses were performed with SPSS 17 (SPSS,
Chicago, Illinois, USA). Baseline characteristics were described
as the means and standard errors of the mean in brackets. Group
differences in mood scores, and in pre-exercise and postexercise levels of hormones were tested using analysis of variance.
Logistic regression with a forward conditional procedure was
used to distinguish NFOR players from controls. A sample size
of 21 players allowed us to use a maximum of two hormones
as predictors. Goodness of fit for logistic regression models was
tested using the Hosmer–Lemeshow test. Collinearity statistics
(variance inflation factor (VIF) and tolerance) were provided as a
test for the independence of the predictors in the logistic regression model. Sensitivity, specificity and area under the curve
(AUC) were provided as indicators of the quality of the classifications. The significance level was set at p<0.05.
Seven NFOR players were invited to the laboratory: age (years)
17.1 (0.3), height (cm) 173.3 (2.0) and body weight (kg) 69.9
(2.7). The control group consisted of 14 players: age (years) 17.1
(0.2), height (cm) 179.6 (1.8) and body weight (kg) 69.2 (1.5).
Only height showed a borderline group difference (p=0.05).
NFOR players with an average submaximal heart rate of 172
beats/min showed an average 6% increase of their submaximal
heart rate response (10 beats/min±5) during the ISRT.
Exercise test
Mood profile
A graded maximal exercise test until exhaustion was performed
on a treadmill to induce acute fatigue. Players were encouraged
to run to exhaustion. The tests were performed between 13:00
and 15:00 p.m. All subjects started with a 3-min warm-up at
8 km/h. Every 2 min, the speed increased by 1 km/h starting
The group of NFOR players scored significantly higher on anger
(p=0.00) and depression (p=0.03), whereas a trend towards a
higher score was found on tension (table 1). Although depression scores were 5.3 times higher in NFOR compared with
controls, the smaller significance compared with anger was
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Original article
Table 2 Average pre-exercise and postexercise serum hormone levels* in seven NFOR players and
14 controls
0.17 (0.02)
6.64 (1.89)
21.14 (4.05)
22.57 (2.05)
0.22 (0.02)
0.28 (0.02)
35.80 (10.23)
44.20 (6.44)
51.00 (10.80)
91.50 (8.81)
0.25 (0.04)
0.31 (0.03)
*ACTH in ng/l, C in µmol/l, GH in µg/l; SEM in brackets.
†Significant group difference (p<0.05).
‡Significant pre-postexercise difference in NFOR and controls (p<0.05).
ACTH, adrenocorticotropic hormone; C, cortisol; GH, growth hormone; NFOR, non-functional over-reaching.
Figure 1 Pre-exercise growth hormone levels in non-functional over-reaching players and controls.
caused by the large variation in the depression scores in the
NFOR group. Age, height and body weight were not associated
with scores on any of the POMS scales.
Pre-exercise levels
Only pre-exercise GH levels showed a statistically significant
difference between groups (p=0.03, table 2). Figure 1 shows
the individual data of pre-exercise levels of GH, the soccer
players, explaining the difference between both groups.
Pre-exercise C levels showed a tendency to be higher in controls (p=0.09, table 2). However, as shown in figure 2, these
C levels did not increase with increasing levels of ACTH in
the NFOR players. This is in contrast with the control players who showed a clear relationship between ACTH and C
(r=0.75, p=0.00). Age, height and body weight did not correlate
with pre-exercise hormone levels.
Postexercise levels
Postexercise, all three hormones were higher in controls, but
only ACTH showed large enough group differences to reach
statistical significance (p=0.01, table 2). Age, height and body
weight were not correlated with hormone levels, except for the
height on postexercise C (r=0.46, p=0.04). Compared with preexercise levels, ACTH and GH levels increased significantly
after the exercise test in both groups (NFOR: ACTH p=0.04,
GH p=0.01; controls: ACTH p=0.00, GH p=0.00). Only the
postexercise increase of ACTH levels showed a significant
group effect (p=0.02, see table 2).
Prediction of NFOR with pre-exercise and postexercise
hormone levels
In a logistic regression model, the pre-exercise GH levels and
postexercise ACTH levels classified all but a single control soccer player correctly (overall 95% correct, sensitivity 100%,
specificity 93%). With both hormones in the regression equation, the two regression coefficients showed a negative relation with the NFOR status. The AUC in the receiver operating
characteristic graph was 99% and the model goodness of fit
was high (χ2 =23.0 at p=0.00). Tolerance and VIF were close to
one. The only control soccer player who was erroneously classified as an NFOR did show a high level of postexercise ACTH
typical for control players. However, he also showed a low
level of pre-exercise GH, which is typical for NFOR players.
Schmikli SL, de Vries WR, Brink MS, et al. Br J Sports Med (2011). doi:10.1136/bjsports-2011-090492
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Figure 2 Pre-exercise C as the function of pre-exercise adrenocorticotropic hormone in non-functional over-reaching players and controls.
Apart from a performance decrease as a primary criterion,
NFOR soccer players in this study also showed a deteriorated mood with increased anger and depression score. The
results on mood differences parallel the earliest reports
about mood changes in overtraining by Morgan et al, 26 for
example, describing female swimmers after 4 weeks overload with significantly increased anger and depression
scores. However, in the Morgan article, 26 studies with similar short-term overload periods also showed that mood rapidly responded to the periods of increased training load, as
well as to tapering during macrocycles. To prevent overestimation of the severity of this type of overload, one could
choose to monitor mood on a frequent basis and for longer
period of time, including taper periods. Alternatively, the
interpretation of mood changes could be paired with a performance assessment, given that a more severe imbalance
between load and recovery will likely increase the risk of a
deteriorated mood and performance. 7 The latter method is
integrated in our study design, supporting the conclusion of
an imbalance between (physical and mental) load and recovery in NFOR soccer players.
It is assumed that the resting levels of C do not change
in short-term overtraining/over-reaching. 7 According to the
defi nition, as discussed in the introduction, a short-term
overtraining/over-reaching does no last more than 4 weeks.
However, our NFOR players were included with a performance decrease lasting at least 1 month (but with a maximum of 2 months), indicating that they had passed the state
of short-term overtraining/over-reaching. In overtrained
athletes, reduced resting C levels have been confi rmed.6 27 28
Compared with controls, the pre-exercise levels of C in
the NFOR players were close to significantly reduced, and
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differed only marginally from what was found in our previous study with a mixed sample of subjects. 29
A significant interaction of the resting ACTH with C levels
was found only in controls, suggesting that a decoupling of C
to ACTH may exist in NFOR players. However, the interaction
in the controls did not significantly differentiate the NFOR
players from controls.
Until now, no studies confi rmed the changes in resting
GH levels in the over-reached or overtrained athletes. In our
controls, GH levels of six control players exceeded 5 μg/l. In
contrast, none of the NFOR players showed GH levels above
0.5 μg/l (see fi gure 1), explaining the significant difference
between both groups (see table 2). As the results of the field
performance tests in NFOR players indicate a reduced physical
fitness, the observed significant difference for the preexercise
levels of GH may be related to differences in physical fitness
between both groups. 30 This is in line with the observations
that improving physical fitness by training enhances GH
secretion. 31 In addition, these data indicate that control players may profit from more anabolic action of GH than NFOR
players. In a training experiment with horses, 32 the authors
induced a form of FOR at the end of the training period as no
clear drop of performance was found. The intensively trained
(IT) horses, however, showed acute compensating anabolic
effects: more frequent and amplified nocturnal peaks in GH,
reflecting an adaptational process to restore homeostasis.
Possibly, our control players also displayed active recovery
similar to the IT horses, with our NFOR players lacking the
ability to produce this compensatory effect.
It is often stated that reduced pituitary and adrenal activity after physical or mental stress may be a hallmark in
overreached and overtrained athletes. 3 13 32–34 In this study,
a reduced pituitary activity was only confi rmed with the
Schmikli SL, de Vries WR, Brink MS, et al. Br J Sports Med (2011). doi:10.1136/bjsports-2011-090492
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Original article
Competing interests None.
What is already known on this topic
Ethics approval CCMO The Hague and local Medical Ethics Committee, Utrecht,
The Netherlands.
In contrast to the functionally over-reached athletes, nonfunctionally over-reached (NFOR) athletes share prolonged
periods of reduced performance, mood problems and neuroendocrine disturbances. Early recognition of NFOR may be
the key to the timing in a successful prevention of the overtraining syndrome. Until now, there is no valid instrument to
diagnose NFOR in athletes.
Provenance and peer review Not commissioned; externally peer reviewed.
What this study adds
A prolonged reduction of the performance with worsened
mood, a reduced anabolic activity at rest and a reduced
pituitary activation after maximal exercise are characteristic
for NFOR in elite junior soccer players. Pre-exercise growth
hormone and postexercise adrenocorticotropic hormone
levels have shown a strong potential to define a diagnostic
criteria for NFOR.
postexercise ACTH response in NFOR players, which was
only 43% of the response in controls. The postexercise GH
and C levels in both groups indicate that the pituitary–adrenal responses were similar. Therefore, the hypothesis that
ACTH, C and GH responses to physical stress should be
reduced could only partially be confi rmed. However, a reduced
adrenal activity cannot be excluded, because lower postexercise C levels in NFOR players may have been obscured by
our laboratory protocol. Our protocol is compatible with the
laboratory protocol used in previous studies,11 16 17 35 which
means that blood was taken to measure the C levels within
minutes after maximal performance. However, it is well
known that maximal C responses to exercise are delayed by
as much as 30 min, 36 indicating that true maximal C levels
may still be reduced in NFOR players. In future studies, we
will apply a modified protocol allowing for an added C test
30 min after maximal exercise to further explore pituitaryadrenal responses in NFOR.
Despite the fact that the number of cases only allowed for
two diagnostic parameters in the logistic regression procedure, the distinguishing qualities of a model with preexercise
GH and postexercise ACTH are very good. Low preexercise
GH levels indicate that NFOR players are compensating for
an imbalance between load and recovery with reduced anabolic activity at rest, whereas under stress low ACTH levels
reveal a partial collapse of the pituitary-adrenal axis. This
illustrates the neuroendocrine signals of an initial, overtrained (NFOR) state, associated with a reduced performance
and worsened mood in young elite soccer players. However,
more research is necessary to prove that this model is valid
and reliable before it can be put into practice. Furthermore,
the development of a similar diagnostic model in male and
female athletes from different types of sports will demand
additional and specific data.
Acknowledgement The authors wish to thank Dr Adam Weir for his assistance
in writing this manuscript.
Funding Funding has been received by ZonMw, the Hague (project number
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Schmikli SL, de Vries WR, Brink MS, et al. Br J Sports Med (2011). doi:10.1136/bjsports-2011-090492
Downloaded from bjsm.bmj.com on April 5, 2012 - Published by group.bmj.com
Monitoring performance, pituitary−adrenal
hormones and mood profiles: how to
diagnose non-functional over-reaching in
male elite junior soccer players
Sándor L Schmikli, Wouter R de Vries, Michel S Brink, et al.
Br J Sports Med published online December 14, 2011
doi: 10.1136/bjsports-2011-090492
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