Diagnosing Overtraining Syndrome: A Scoping Review: Context

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1044739

research-article2021
SPHXXX10.1177/19417381211044739Carrard et alSports Health

vol. 14 • no. 5 SPORTS HEALTH

Diagnosing Overtraining Syndrome:


A Scoping Review
Justin Carrard, MD,*† Anne-Catherine Rigort, BSc,† Christian Appenzeller-Herzog, PhD,‡
Flora Colledge, PhD,§ Karsten Königstein, MD,† Timo Hinrichs, MD,†
and Arno Schmidt-Trucksäss, MD†

Context: Overtraining syndrome (OTS) is a condition characterized by a long-term performance decrement, which occurs
after a persisting imbalance between training-related and nontraining-related load and recovery. Because of the lack of a
gold standard diagnostic test, OTS remains a diagnosis of exclusion.
Objective: To systematically review and map biomarkers and tools reported in the literature as potentially diagnostic for
OTS.
Data Sources: PubMed, Web of Science, and SPORTDiscus were searched from database inception to February 4, 2021,
and results screened for eligibility. Backward and forward citation tracking on eligible records were used to complement
results of database searching.
Study Selection: Studies including athletes with a likely OTS diagnosis, as defined by the European College of Sport
Science and the American College of Sports Medicine, and reporting at least 1 biomarker or tool potentially diagnostic for
OTS were deemed eligible.
Study Design: Scoping review following the guidelines of the Joanna Briggs Institute and PRISMA Extension for Scoping
Reviews (PRISMA-ScR).
Level of Evidence: Level 4.
Data Extraction: Athletes’ population, criteria used to diagnose OTS, potentially diagnostic biomarkers and tools, as well
as miscellaneous study characteristics were extracted.
Results: The search yielded 5561 results, of which 39 met the eligibility criteria. Three diagnostic scores, namely the
EROS-CLINICAL, EROS-SIMPLIFIED, and EROS-COMPLETE scores (EROS = Endocrine and Metabolic Responses on
Overtraining Syndrome study), were identified. Additionally, basal hormone, neurotransmitter and other metabolite levels,
hormonal responses to stimuli, psychological questionnaires, exercise tests, heart rate variability, electroencephalography,
immunological and redox parameters, muscle structure, and body composition were reported as potentially diagnostic for
OTS.
Conclusion: Specific hormones, neurotransmitters, and metabolites, as well as psychological, electrocardiographic,
electroencephalographic, and immunological patterns were identified as potentially diagnostic for OTS, reflecting its
multisystemic nature. As exemplified by the EROS scores, combinations of these variables may be required to diagnose OTS.
These scores must now be validated in larger samples and within female athletes.
Keywords: overtraining syndrome; athletes; diagnosis; biomarkers; tools

From †Division of Sports and Exercise Medicine, Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland, ‡University Medical Library, University of
Basel, Basel, Switzerland, and §Division of Sports Science, Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland
*Address correspondence to Justin Carrard, MD, Division of Sports and Exercise Medicine, Department of Sport, Exercise and Health, University of Basel, Birsstrasse 320B,
Basel, CH-4052, Switzerland (email: justin.carrard@unibas.ch) (Twitter: @CarrardJustin).
The authors report no potential conflicts of interest in the development and publication of this article.
DOI: 10.1177/19417381211044739
© 2021 The Author(s)

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Carrard et al Sep • Oct 2022

A
n overload in training is believed to be a necessary PRESS (Peer Review of Electronic Search Strategies) reviewed by
stimulus to enhance athletic performance.39 However, an information specialist.51
adequate recovery balancing training and overall stress The search was conducted on February 19, 2020, and updated
level are at least as important as training itself as an imbalance on January 20 and February 4, 2021. Retrieved references were
between training and recovery might lead to a decrement in exported to EndNote X9 and duplicates were removed. Two
performance.31,39 Functional overreaching is defined as a short- authors independently reviewed titles and abstracts against the
term decrease in performance (usually up to 2 weeks) followed selection criteria and deemed them as “include,” “exclude,” or
by a supercompensation effect (adaptive improvement in “uncertain.” Discrepancies were resolved by discussion and
performance).52 In cases where the performance decrement is consensus between the 2 authors, and with a third party in case
of a slightly longer duration (usually up to 3-4 weeks) and not a resolution could not be arrived at. For titles and abstracts
followed by supercompensation, the term nonfunctional marked as “include” or “uncertain,” the corresponding full-text
overreaching is used.52 Finally, if reduced performance capacity articles were retrieved and reviewed independently by 2 authors
lasts for more than 3 to 4 weeks and is followed by neither for inclusion against the selection criteria.
supercompensation nor improved athletic performance, To complement the results of direct database searching, the
the athlete is likely experiencing an overtraining syndrome bibliographic references of all included articles (backward
(OTS).52 citation tracking), as well as the citing articles of those which
Not only can OTS endanger athletes’ health, its detrimental are indexed in Scopus or the Web of Science (forward citation
effects can also extend to their career.32 Athletes suffering from tracking), were screened.
OTS might never again reach their previous level of
performance.6 With a prevalence of around 30% at age 15 years Eligibility Criteria
within young English athletes across different sports, OTS is not Inclusion criteria included (1) original articles published until
infrequent.50 Because of the lack of a gold standard diagnostic the date of last search, that is, February 4, 2021; (2) studies on
test, OTS remains a challenging diagnosis of exclusion.52 humans only; (3) involving athletes with a diagnosis of OTS, as
While systematic reviews aim to answer precise research defined in the joint consensus statement by the European
questions, scoping reviews are appropriate to systematically College of Sport Science and the American College of Sports
summarize a field of research that has not been Medicine52; and (4) reporting at least 1 potential diagnostic test
comprehensively reviewed yet.59 With only 1 systematic review for OTS. Exclusion criteria included (1) nonoriginal articles; (2)
investigating the hormonal aspects of OTS, this field has studies written in a language other than English, French, or
exclusively been narratively reviewed to date.11 Therefore, our German (as authors have native-speaking expertise in these 3
study aims to systematically review the current literature and languages); and (3) studies about medical conditions mimicking
map biomarkers and tools reported as potentially diagnostic of signs and/or symptoms of OTS.
OTS. In agreement with pertinent guidelines, this scoping
review will not assess individual study quality.59 Data Charting
The following information was extracted from the selected
Methods articles and mapped: (1) authorship, (2) publication date, (3)
study design and duration, (4) studied population, (5) criteria
Protocol and Registration
used to diagnose OTS, and (6) biomarkers and tools reported as
The present scoping review followed the guidelines of the potentially diagnostic of OTS.
Joanna Briggs Institute and the PRISMA (Preferred Reporting
Items for Systematic Reviews and Meta-Analyses) Extension for Results
Scoping Reviews (PRISMA-ScR).59,69 The protocol was registered
on Open Science Framework on February 18, 2020.19 Study Selection
The search yielded unique 5561 results, of which 39 met the
Search Strategy and Studies Selection eligibility criteria (Figure 1). The authors agreed on all eligibility
The search strategy was developed in collaboration with an decisions on discussion without the need for a third party to be
information specialist. Initial searches in PubMed were involved. Of note, 2 studies were included even though the
performed to identify articles on the topic. Words in titles and inspected athletes were diagnosed by the authors with chronic
abstracts, MeSH (medical subject heading) terms, and author fatigue syndrome and nonfunctional overreaching, respectively,
keywords were analyzed. Results of this initial search were used as the pathological profiles described in these older publications
to develop single-concept OTS search strings for both PubMed matched the most recent OTS definition from 2013.52,57,65
and Web of Science (Appendix 1, available in the online version Forward and backward citation tracking of the 39 included
of this article). As there is no OTS-specific MeSH term, both publications did not yield any additional publications.
strings were exclusively based on text word synonyms. In
addition, SPORTDiscus was searched via EBSCOhost using a Characteristics of Included Studies
combination of subject headings and text word synonyms of The 39 included publications correspond to 30 independent
OTS (Appendix 1, available online). All search strings were studies (Appendix 2, available online; 3 studies were reported

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Addional records idenfied


Records idenfied through through other sources

Identification
database searching (n = 0)
(n = 6918) Update of literature
(n = 216)

Records aer duplicates removed


(n = 5561)
Screening

Records screened Records excluded


(n = 5561) (n = 5458)

Full-text arcles assessed Full-text arcles excluded


for eligibility - Out of scope (n = 59)
Eligibility

(n = 103) - Arcle not available (n = 4)


- In Portuguese (n = 1)

Studies included
Included

(n = 39)

Figure 1.  Study selection process according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)
flowchart.

in eight,7-9,12,13,15-16-17 two36,37 and two43,44 publications,


respectively). For ease of interpretation, studies’ characteristics Table 1.  Number of studies per type of sport
are based on the 30 included studies, while biomarkers and
tools are reported relatively to the 39 included publications. No. of Studies (of Which
Thirty-seven publications were written in English and 2 were Type of Sport Case Reports)
written in French.4,24 Publication year ranges from 1985 to 2020. Multiple 19
Sports Performed Not specified 2 (1)
As displayed in Table 1, 19 studies examined athletes from
Rowing 3 (1)
different sports,1,2,4-9,12,13,15-17,20,24,29,36,37,43-45,53,54,58,64,66,68,72 while 9
studies focused on 1 single sport. Two studies did not disclose Cross-country skiing 2 (1)
the type of sport played.42,71 In terms of athletes per sport,
Triathlon 1
running followed by endurance exercise (not further specified
in the studies) and rowing were the most frequently examined Speed skating 1
sports (Table 2).
Swimming 1 (1)
Athletes and Control Group
Cycling 1 (1)
In total, 952 subjects were examined including 328 athletes
diagnosed with OTS and 624 healthy control subjects. In 24
studies, the athletes were already previously affected by
OTS,2,4-9,12,15-17,20,24,29,30,34,36,37,42-45,47,53,54,56-58,64,65,68,72 while in 6 group,4,24 and 5 studies were case-reports with only 1 subject
studies, OTS developed during the study.1,27,60,61,66,71 A total of 7 and no control.30,47,56,65,71 Eighteen studies enrolled
studies were uncontrolled: 2 studies did not have any control healthy athletes as controls,1,2,5,6,19,29,34,36,37,42,45,54,57,58,60,61,66,68,72

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Carrard et al Sep • Oct 2022

Table 2.  Number and proportion of subjects per type of sport

OTS-Affected Subjects Control Group Subjects All Subjects


Type of Sport Performed n Proportion, % n Proportion, % n Proportion, %
Not specified (multiple/unknown) 123 37.5 333 53.4 456 47.9
Running 40 12.2 39 6.3 79 8.3
Endurance exercise 43 13.1 30 4.8 73 7.7
Rowing 25 7.6 39 6.3 64 6.7
Swimming 17 5.2 24 3.8 41 4.3
CrossFit 9 2.7 22 3.5 31 3.3
Cross-country skiing 5 1.5 22 3.5 27 2.8
Speed skating 3 0.9 22 3.5 25 2.6
Triathlon 13 4.0 10 1.6 23 2.4
Cycling 6 1.8 14 2.2 20 2.1
Endurance and resistance exercise 5 1.5 3 0.5 8 0.8
Race walking 4 1.2 4 0.6 8 0.8
Resistance exercise 8 2.4 0 0 8 0.8
Ice hockey 7 2.1 0 0 7 0.7
Sprint running 1 0.3 4 0.6 5 0.5
Squash 3 0.9 2 0.3 5 0.5
Wrestling 4 1.2 0 0 4 0.4
Football 3 0.9 0 0 3 0.3
Motocross 2 0.6 0 0 2 0.2
Orienteering 2 0.6 0 0 2 0.2
Ballet 1 0.3 0 0 1 0.1
Biathlon 1 0.3 0 0 1 0.1
Rugby 1 0.3 0 0 1 0.1
Surfing 1 0.3 0 0 1 0.1
Tennis 1 0.3 0 0 1 0.1
Sedentary 0 0 56 9.0 56 5.9
Total 328 100 624 100 952 100

OTS, overtraining syndrome.

3 studies had both healthy athletes and sedentary subjects as As shown in Table 3, 14 studies included both men and
controls,7-9,12,13,15-17,27,43,44 1 study had sedentary controls only,64 women.2,4-6,20,24,36,37,42,45,53,64,66,68,72 Ten studies, of
and 1 study compared OTS-affected athletes to athletes suffering which 3 were case reports, focused on men
from nonfunctional overreaching.53 only1,7-9,12,13,15-17,27,30,34,54,56,60,61,71 and 2 studies, of which

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Table 3.  Sex distribution among groups

OTS-Affected Subjects Control Group Subjects Overall


Absolute Absolute Absolute
Sex number Proportion, % number Proportion, % number Proportion, %
Unknown 91 27.8 398 63.8 489 51.4
Male 155 47.3 175 28.0 330 34.7
Female 82 25.0 51 8.2 133 14.0
   
Total 328 100 624 100 952 100

OTS, overtraining syndrome.

1 was a case report, on women only.47,57 Four studies did test (TBE, n = 4),6,53,54,57 which consists of 2 consecutive
not specify participants’ sex.29,43,44,58,65 The duration of incremental exercise protocols to exhaustion with 4 hours of rest
performance decrement was at least 3 weeks in all the studies in between.54 Blunted response to ITT in OTS-affected compared
included. with healthy athletes was reported for ACTH (n = 5),1,7,13,15,16
cortisol (n = 5),1,7,13,15,17 GH (n = 5),1,7,12,15,17 and PRL (n = 4).1,7,12,17
Findings From the Selected Publications Response to the first and second bouts of TBE was, respectively,
Diagnostic Scores reported to be increased and blunted for both ACTH and
Three diagnostic scores, namely the EROS-CLINICAL, EROS- PRL.6,53,54 GH response to both bouts was reported to be blunted
SIMPLIFIED, and EROS-COMPLETE scores, were identified (n = 2).53,54 Cortisol response to both bouts was described as
(Appendix 3, available online).7 As indicated in Appendix 3 slightly increased (n = 2).54,57 Maximal lactate concentration less
(available online), the EROS-CLINICAL score is based on clinical than 8 mmol/L at the end of both bouts showed high sensitivity
items only, the EROS-SIMPLIFIED score includes clinical and for OTS.53 Finally, decreased VO2peak, maximum workload, and
biochemical tests, while the EROS-COMPLETE score consisted anaerobic threshold as well as increased perception of effort
of clinical, biochemical, insulin tolerance test (ITT), and body were evidenced in an ultra-endurance cyclist suffering from OTS
composition variables.7 Combined in a decision tree, these 3 compared with his own previous values.65
scores could distinguish all apparently OTS-affected from
healthy male athletes in the original study.7 Psychological Questionnaires
Psychological questionnaires used to distinguish OTS-affected
Basal Hormone Levels from control groups included the Profile of Mood States (POMS,
Basal hormone levels, defined as hormone levels in a n = 10),6,7,9,15-17,29,30,34,57 the overtraining questionnaire of the
resting state, were the most frequently assessed Société française de médecine du sport (French Society of Sport
biomarkers, as they were used to identify OTS in 17 Medicine, SFMS, n = 2),4,24 the Hamilton Depression Scale
publications.1,7,8,13,15-17,27,30,34,42,53,54,56,58,64,66 As indicated in (HAMD) and Montgomery-Åsberg Depression Rating Scale
Appendix 3 (available online), the most common hormonal (MADRS, n = 1),72 as well as the Recovery Stress Questionnaire
alterations observed in OTS-affected compared with healthy for Athletes (RESTQ-Sport, n = 1).56 Reported differences in
athletes were the following: diminished serum testosterone to POMS within OTS-affected compared with healthy athletes
estradiol ratio (n = 4),7,8,15,16 diminished circulating testosterone included increased total POMS score (n = 4),9,17,30,34 fatigue score
level (n = 3),7,17,56 elevated serum estradiol level (n = 3),8,16,17 (n = 5),7,9,16,29,30 tension score (n = 3),7,15,34 anger score (n =
elevated plasma and salivary cortisol level (n = 4),1,13,30,53 3),7,29,34 depression score (n = 2),29,34 confusion score (n = 2),29,30
elevated nocturnal urinary catecholamines (n = 3),8,16,17 elevated as well as decreased vigor score (n = 4).7,9,15,29 An SFMS score
plasma adrenocorticotropic hormone (ACTH) level (n = 2),53,54 ≥20 was reported to be indicative of OTS.4,24 The HAMD and
diminished serum prolactin (PRL) level (n = 2),7,12 and MADRS depression scales, as well as the RESTQ-Sport, appeared
diminished serum growth hormone (GH) level (n = 2).7,12 to be elevated in OTS-affected compared with healthy athletes.57,72

Responses to Stimuli Heart Rate Variability

Hormonal response to stimuli was evaluated in a total of 11 High and low periodic oscillations (ie, high and low frequency)
publications using either ITT (n = 7)1,7,12,13,15-17 or 2-bout exercise of the RR interval (interval between QRS complexes of normal

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sinus depolarizations)67 were elevated (n = 2)34,36 and reduced, within OTS-affected compared with healthy athletes.7,15,42 Similar
respectively (n = 3),34,36,37 in OTS-affected versus healthy alterations were reported in OTS-affected CrossFit athletes.17
athletes. This speaks in favor of parasympathetic dominance.
Conversely, 1 study reported elevated low frequency in OTS- Electroencephalography
affected athletes and sedentary controls compared with well- Differences in electroencephalography (EEG) features were
trained athletes.43 observed between 100 OTS-affected athletes and 100 healthy
subjects.2 OTS-affected athletes were characterized by decreased
Metabolic Alterations α-index, increased amplitude of β-waves, and slow wave
One study used Fourier transform infrared spectroscopy, a occurrence (mainly θ-waves). Hyperventilation-induced EEG-
technique using a mathematical process (Fourier transformation) responses in OTS-affected athletes included increased number
to obtain an infrared absorption spectrum of a solid, liquid, or of slow waves, increased slow wave index and blunted increase
gas,25 to investigate serum metabolic alterations in response to of α-wave amplitude. During exercise, α-wave amplitude
exercise.60 Two rowers displayed a disturbed saccharide increased in the control group, while no change was evidenced
absorption spectrum after 5 weeks of training, followed by in the OTS group.
abnormal lipid and peptide absorption spectra on weeks 8 and
15, respectively, before being clinically diagnosed with OTS on
Discussion
week 15. The disturbed peptide metabolism persisted until the
end of the study (week 37). Rowers suspected of suffering from The present work systematically reviewed and mapped tools
nonfunctional overreaching were asked to rest before abnormal and biomarkers that are potentially diagnostic for OTS. The
peptide absorption spectra appeared, and clinically recovered in obtained results are summarized in Figure 2. The diversity of the
3 weeks. A disturbed peptide absorption spectrum was tools and biomarkers identified in the present work highlights
considered diagnostic for OTS. Plasma lipid profile was also the fact that OTS affects multiple body systems.52 This diversity
reported to be altered in OTS-affected athletes, characterized by could also support the hypothesis made by Cadegiani et al7 that
an increase in glycerol and a decrease in triglycerides, very low- OTS is an heterogenous clinical entity whose symptomatic
density lipoprotein and apolipoprotein C3 concentration.61 presentation varies between athletes.
Diminished glutamine levels (n = 2),58,64 elevated glutamate Cadegiani et al7 conducted the Endocrine and Metabolic
levels (n = 2)58,66 as well as diminished glutamine to glutamate Responses on Overtraining Syndrome (EROS) study, which
ratio (n = 1)66 were evidenced in plasma in resting state. resulted in 11 publications.7-10,12-18 They evaluated 117 potential
Additionally, higher levels of serum creatine kinase were also OTS markers and concluded that individually none of the
reported within OTS-affected compared with healthy athletes.8,15 markers accurately distinguished OTS-affected from healthy
athletes.7 Combining the most promising markers, they
Neurotransmitters elaborated 3 diagnostic scores, namely the EROS-CLINICAL,
Decreased sensitivity of serotonin receptors was reported in EROS-SIMPLIFIED, and EROS-COMPLETE scores, which could
OTS-affected athletes compared with well-trained controls,5 distinguish all apparently OTS-affected from healthy male
while a reduced number of serotonin transporters was found in athletes, once combined in a decision tree.7 While Cadegiani
a single OTS-affected and depressed team athlete using single- et al7 reported a 100% diagnostic accuracy of these scores in the
photon emission computed tomography.71 The latter was EROS study, this claim lacks a firm methodological foundation
interpreted as decreased serotonin production and release.71 because of the absence of a gold standard diagnostic test for
OTS. Furthermore, these scores should now be validated in
Immunological and Redox Parameters larger samples and female athletes as highlighted by Cadegiani
The ratio of neutrophils to lymphocytes was shown to be et al.7 Other markers such as heart rate variability (HRV)
decreased,15 while interleukin (IL)-1β, IL-6, and tumor necrosis variables or metabolite levels could be considered as potential
factor-α were elevated in response to a single exercise bout.42 additional items of the EROS scores.
Alterations in redox homeostasis, characterized by increased The autonomous nervous system hypothesis posits dominance
oxidant and reduced antioxidant capacities, were reported.44,47,68 of parasympathetic activation and decreased sympathetic
Specifically, markers of protein oxidation and total oxidant activation to be the underlying cause of the symptoms
capacity were elevated, while antioxidants such as red blood experienced in OTS.46 Although comparing HRV data from
cell glutathione, coenzyme Q10, γ-tocopherol, and carotenoids different studies is challenging because of methodical
were diminished.44,47,68 heterogeneity, the findings of the present work support, at least
partly, the autonomous nervous system hypothesis.32,52 Namely,
Muscular Alterations and Body Composition elevated high-frequency power and reduced low-frequency
Diminished telomere lengths,20 focal necrosis, and myofibrillar power were observed within OTS-affected compared with
disorganization65 were observed within muscle fibers of OTS- healthy athletes.34,36,37
affected compared with nonaffected athletes. Lower muscle Alteration in metabolite levels represents another promising
mass and body water as well as higher fat mass were observed field of research. In addition to their roles as building blocks of

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Figure 2.  Overview of the identified biomarkers and tools potentially diagnostic of overtraining syndrome (OTS). CPX,
cardiopulmonary exercise test; EEG, electroencephalography; HRV, heart rate variability; ITT, insulin tolerance test; POMS, Profile of
Mood State; psy. questionnaires, psychological questionnaires; TBE, 2-bout exercise test.

cell components and fuels in cellular energetics, metabolites also questionnaires (SFMS, HAMD, MADRS, and RESTQ-Sport).
act as signaling molecules and driving forces in the Importantly, psychological questionnaires applied in isolation
pathophysiology of human diseases.63,73 The successive are probably more useful in the monitoring of both the training
alterations reported in saccharide, lipid, and peptide absorption and recovery processes than in the diagnosis itself.32
spectra along the fatigue continuum are preliminary in nature Neurobiologically, the reported diminished serotonin receptors’
and cannot yet be used in the diagnostic process of OTS. These sensitivity and transporters’ number are compatible with the
findings should pave the way for future research investigating observed psychological patterns.23,55
the metabolic determinants of OTS. Novel technologies such as A potential diagnostic tool that has not received much
metabolomics, a powerful metabolic phenotyping tool, could attention so far is EEG. A variety of EEG patterns were reported
improve OTS-affected athletes’ profiling and ultimately contribute to be different between OTS-affected athletes and healthy
to the discovery of novel biomarkers.40 For instance, diminished subjects. As EEG is noninvasive and relatively inexpensive,
glutamine and elevated glutamate levels have often been linked further research in this promising field is warranted. Similarly,
to impaired immune system within athletes suffering from a diminished telomere length in muscle cells represents another
disorder of the continuum fatigue spectrum.22,33,38,66 sparsely researched feature observed in OTS-affected athletes.
Basal hormone levels were frequently reported to be altered While reduction in telomere length naturally occurs with aging,
in OTS-affected compared with healthy athletes. Catabolic certain factors such as exercise-related muscle damage can
hormones, such as cortisol and catecholamines, tended to be accelerate this process.48 Interestingly, telomere length was
elevated, while anabolic hormones, such as testosterone and inversely correlated to the number of running years and training
estradiol, showed conflicting results. Several authors believe that hours.62 Whether telomere length responds differently to
hormonal responses to stimuli are more accurate than basal physiological training adaptation and pathological training
hormone levels in diagnosing OTS.11,70 Hormone levels did maladaptation remains to be determined.
behave more homogenously on stimulation with ACTH, PRL,
GH, and insulin-like growth factor-1 (IGF-1) being blunted in Limitations
response to ITT or exercise stimuli within OTS-affected The field of OTS research faces several hurdles. First, the lack of
compared with healthy and overreached athletes. Only cortisol standard definitions and terminologies in OTS, coupled with the
levels showed varied responses. OTS-affected athletes displayed fact that distinctions between nonfunctional overreaching and
dysfunctions in the hypothalamus-pituitary-adrenal axis in OTS are not always straightforward, make it difficult to
response to a stress situation.13,54 These dysfunctions are likely characterize athletes that show a decrement in performance and
to be central (either in the hypothalamus and/or the pituitary), ultimately compare studies.52 Consequently, clinical studies
since the adrenals were reported to respond physiologically to investigating OTS should be viewed in this context and
ACTH stimulation tests in OTS-affected athletes.13 interpreted with caution. Second, conclusions of most included
Psychological questionnaires have long been used in the OTS reports are limited by small samples sizes.32 Of the 39
research field, as mood disturbances are common in OTS- publications included for this scoping review, 8 were based on
affected athletes. These athletes tend to display higher total only 1 single subject. As a result, the overall quality of the
POMS score, higher fatigue, tension, depression, anger, and scientific evidence is low, that is, level 4.
confusion subscores as well as a lower vigor subscore. Similar Athletes engaged in endurance sports were clearly
psychological patterns were observed using other psychological overrepresented in the included publications. Although both

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Carrard et al Sep • Oct 2022

endurance and non-endurance athletes are at risk for OTS,49 this 8. Cadegiani FA, Kater CE. Basal hormones and biochemical markers as predictors
of overtraining syndrome in male athletes: the EROS-BASAL study. J Athl Train.
overrepresentation is common in the OTS research field.28,52 2019;54:906-914.
Interestingly, differences were observed between OTS-affected 9. Cadegiani FA, Kater CE. Body composition, metabolism, sleep, psychological
athletes engaged in endurance and resistance sports26 with and eating patterns of overtraining syndrome: results of the EROS study (EROS-
PROFILE). J Sports Sci. 2018;36:1902-1910.
catecholamine levels being decreased in the former but 10. Cadegiani FA, Kater CE. Enhancement of hypothalamic-pituitary activity in male
increased in the latter.11 Therefore, diagnostic tools and athletes: evidence of a novel hormonal mechanism of physical conditioning.
biomarkers for OTS might need to be specific to the type of BMC Endocr Disord. 2019;19:117.
11. Cadegiani FA, Kater CE. Hormonal aspects of overtraining syndrome: a
sport.28 systematic review. BMC Sports Sci Med Rehabil. 2017;9:14.
Female athletes are underrepresented in OTS studies, as is the 12. Cadegiani FA, Kater CE. Hormonal response to a non-exercise stress test in
case in much of sports and exercise medicine research.21 The athletes with overtraining syndrome: results from the Endocrine and metabolic
Responses on Overtraining Syndrome (EROS)—EROS-STRESS. J Sci Med Sport.
study of female athletes with OTS is complicated by the 2018;21:648-653.
biological complexity of the menstrual cycle.3 Both the phases 13. Cadegiani FA, Kater CE. Hypothalamic-pituitary-adrenal (HPA) axis functioning
of the menstrual cycle and the use of oral contraceptives can in overtraining syndrome: findings from Endocrine and Metabolic Responses
on Overtraining Syndrome (EROS)–EROS-HPA axis. Sports Med Open.
affect hormonal testing in female athletes.35,52 Therefore, to 2017;3:45.
provide female-specific biomarkers and normal values, it is 14. Cadegiani FA, Kater CE. Inter-correlations among clinical, metabolic, and
necessary to not only investigate more female athletes suffering biochemical parameters and their predictive value in healthy and overtrained
male athletes: the EROS-CORRELATIONS study. Front Endocrinol (Lausanne).
from OTS but also consider the hormone fluctuations 2019;10:858.
throughout the menstrual cycle as well as the intake of oral 15. Cadegiani FA, Kater CE. Novel causes and consequences of overtraining
contraceptives.41 syndrome: the EROS-DISRUPTORS study. BMC Sports Sci Med Rehabil.
2019;11:21.
16. Cadegiani FA, Kater CE. Novel insights of overtraining syndrome discovered
Conclusion from the EROS study. BMJ Open Sport Exerc Med. 2019;5:e000542.
17. Cadegiani FA, Kater CE, Gazola M. Clinical and biochemical characteristics of
This scoping review included 39 publications reporting high-intensity functional training (HIFT) and overtraining syndrome: findings
biomarkers and tools potentially diagnostic for OTS. The quality from the EROS study (the EROS-HIFT). J Sports Sci. 2019;37:1296-1307.
18. Cadegiani FA, Silva PHL, Abrao TCP, Kater CE. Novel markers of recovery from
of evidence available was low as indicated by level 4 rating. The overtraining syndrome: the EROS-LONGITUDINAL study. Int J Sports Physiol
diversity of the identified markers and tools is in line with the Perform. Published online January 5, 2021. doi:10.1123/ijspp.2020-0248
fact that OTS affects multiple body systems. Moreover, it 19. Carrard J, Rigort A-C, Hinrichs T, Appenzeller-Herzog C, Schmidt-Trucksäss A.
Diagnosing overtraining syndrome: a scoping review protocol. doi:10.17605/
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