Publications

Overtraining Syndrome


June 27, 2021

HOW “THE CORTISOL AWAKES” TELLS ABOUT HEALTH STATUS IN ATHLETES 

Cortisol releasing patterns after awakening in athletes

THE CORTISOL RESPONSE TO AWAKENING IS IMPAIRED IN ATHELTES AFFECTED BY OVERTRAINING SYNDROME 

This is a post-hoc analysis of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study that compared the Cortisol Awakening Response (CAR) between athletes affected by overtraining syndrome (OTS) and healthy athletes. CAR is a physiological cortisol response that occurs when we wake up. Cortisol levels rise between 30% and 70% between the moment that we open our eyes and 30 minutes after awakening. The study not only compared the salivary cortisol at awakening and 30 minutes after, but also at 4PM and 11PM, in order to determine the salivary cortisol rhythm. We found that athletes with OTS presented a flawed CAR comparing to healthy athletes, which may help explain why OTS-affected athletes typically complain of lack of energy when they wake up, besides the overall reduction in energy levels. Conversely, the cortisol loop during the day until the night was not affected by OTS. 

Links:

https://journals.humankinetics.com/view/journals/ijspp/aop/article-10.1123-ijspp.2020-0205/article-10.1123-ijspp.2020-0205.xml

https://pubmed.ncbi.nlm.nih.gov/33662935/

 

Reference:

Anderson T, Wideman L, Cadegiani FA, Kater CE. Effects of Overtraining Status on the Cortisol Awakening Response-Endocrine and Metabolic Responses on Overtraining Syndrome (EROS-CAR). Int J Sports Physiol Perform. 2021 Mar 3:1-9. doi: 10.1123/ijspp.2020-0205. Epub ahead of print. PMID: 33662935. 

ABSTRACT 

Introduction: The cortisol awakening response (CAR) is a distinct component of the circadian cortisol profile and has promise as a biomarker for the monitoring of athlete readiness and training status. Although some studies have suggested the CAR may be affected by the development of overtraining syndrome (OTS), this has yet to be systematically investigated. 

Purpose: To compare the CAR and diurnal cortisol slope between athletes diagnosed with OTS, healthy athletes, and sedentary controls. 

Methods: This study was a secondary analysis of data from the Endocrine and Metabolic Responses on Overtraining study. Male participants were recruited to either OTS, healthy athlete, or sedentary control groups. The participants produced saliva samples immediately after waking (S1), 30 minutes after waking (S2), at 16:00 hours, and at 23:00 hours. Salivary cortisol concentration was determined by an electrochemiluminescence assay. Mixed-effects models were used to assess the conditional effect of group (sedentary controls, OTS, and healthy athletes) on the change in cortisol over time. Separate models were fit for the awakening samples (S1 and S2) and for the diurnal slope (linear change across S1, 16:00 h, and 23:00 h). 

Results: The models demonstrated significant time-by-group interaction for OTS for the 2 cortisol concentrations collected during the awakening period (β = −9.33, P < .001), but not for the diurnal cortisol slope (β = 0.02, P = .80). 

Conclusions: These results suggest the CAR may be associated with OTS and should be considered within a panel of biomarkers. Further research is necessary to determine whether alterations in the CAR may precede the diagnosis of OTS.

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WE CAN FINALLY DETECT WHEN OVERTRAINED ATHLETES ARE RECOVERING 

 

Recovery from Overtraining Syndrome

MARKERS OF RECOVERY FROM OVERTRAINING SYNDROME HAVE BEEN UNVEILED FOR THE FIRST TIME 

Overtraining syndrome (OTS) is the most common disease related to sports that leads to a paradoxical reduction in sports performance and symptoms direct- and indirectly related to fatigue, which we proposed to be renamed to Paradoxical Deconditioning Syndrome (PDS), since the paradoxical loss of performance is the main hallmark of the syndrome. Until a short time ago, much remained to be clarified regarding the mechanisms that led to OTS, as well as markers of OTS. In the EROS study, more than 30 specific markers of OTS have been discovered. The recovery of OTS is complex and not always complete: many professional athletes are not able to achieve their previous marks. From the markers unveiled for OTS, we were able to detect which markers predict recovery of OTS from a 3-month program and follow-up of OTS-affected athletes. Basically, athletes that presented a better recovery were able to recover the fast hormonal response to stimulation, improve freeT3 levels, normalize the testosterone:estradiol ratio, and improve the Cortisol Awakening Response (CAR). Conversely, the prolonged hormonal response typically observed in healthy athletes was not recovered, as well as markers of body composition and metabolism.

In conclusion, our study showed that the recovery process from OTS is complex, not easy, prolonged, and not full, which corresponds to the long-term consequences that athletes affected by actual OTS experiment. 

Links:

https://journals.humankinetics.com/view/journals/ijspp/aop/article-10.1123-ijspp.2020-0248/article-10.1123-ijspp.2020-0248.xml

https://pubmed.ncbi.nlm.nih.gov/33406484/ 

Reference:

 

Cadegiani FA, Silva PHL, Abrao TCP, Kater CE. Novel Markers of Recovery From Overtraining Syndrome: The EROS-LONGITUDINAL Study. Int J Sports Physiol Perform. 2021 Jan 5:1-10. doi: 10.1123/ijspp.2020-0248. Epub ahead of print. PMID: 33406484

ABSTRACT 

Purposes: Overtraining syndrome (OTS) is an unexplained underperformance syndrome triggered by excessive training, insufficient caloric intake, inadequate sleep, and excessive cognitive and social demands. Investigation of the recovery process from OTS has not been reported to date. The objective was to unveil novel markers and biochemical and clinical behaviors during the restoration process of OTS. 

Methods: This was a 12-week interventional protocol in 12 athletes affected by OTS, including increase of caloric intake, transitory interruption of training, improvement of sleep quality, and management of stress, followed by the assessment of 50 parameters including basal and hormonal responses to an insulin tolerance test and nonhormonal biochemical markers, and body metabolism and composition. 

Results: Early cortisol (P = .023), late ACTH (adrenocorticotrophic hormone) (P = .024), and early and late growth hormone (P = .005 and P = .038, respectively) responses, basal testosterone (P = .038), testosterone:estradiol ratio (P = .0005), insulinlike growth factor 1 (P = .004), cortisol awakening response (P = .001), and free thyronine (P = .069) increased, while basal estradiol (P = .033), nocturnal urinary catecholamines (P = .038), and creatine kinase (P = .071) reduced. Conversely, markers of body metabolism and composition had slight nonsignificant improvements. 

Conclusion: After a 12-week intervention, athletes affected by actual OTS disclosed a mix of non-, partial, and full recovery processes, demonstrating that remission of OTS is as complex as its occurrence.

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THE CLINICAL DIAGNOSIS OF OVERTRAINING SYNDROME 

 

Diagnosis of Overtraining Syndrome

THE FIRST CLINICAL AND BIOCHEMICAL SCORE FOR PRECISE DIAGNOSIS OF OVERTRAINING SYNDROME HAS BEEN VALIDATED AND PUBLISHED 

Because the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study evaluated more than 100 markers in three groups of subjects, of overtrained athletes, healthy athletes, and healthy non-physically active subjects, aiming do distinguish physiological from pathological hormonal and metabolic changes that occur in athletes, it allowed us structure specific scores for diagnosis of overtraining syndrome. The diagnosis of OTS through the proposed scores did not require the presence of late-stage symptoms like loss of performance and unrefreshing rest, which is highly desirable, once the later the diagnosis, the harder the recovery process.

From an internal validation process, we were able to propose scores at different levels of assessments (whether only clinical markers, basal biochemical markers, or stimulated markers) with 100% accuracy to distinguish OTS-affected from healthy athletes.

This paper makes the diagnosis of OTS less subjective, less time-consuming, and less questionable. It is likely a hallmark in the management of athletes suspected for OTS. 

Links:

https://www.hindawi.com/journals/jsm/2020/3937819/

https://pubmed.ncbi.nlm.nih.gov/32373644/ 

Reference:

Cadegiani FA, da Silva PHL, Abrao TCP, Kater CE. Diagnosis of Overtraining Syndrome: Results of the Endocrine and Metabolic Responses on Overtraining Syndrome Study: EROS-DIAGNOSIS. J Sports Med (Hindawi Publ Corp). 2020;2020:3937819. Published 2020 Apr 22. doi:10.1155/2020/3937819.

Study Abstract

ObjectivesOvertraining syndrome (OTS), a common dysfunction among elite athletes, causes decreased performance and fatigue and has no standardized diagnostic criteria. The Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study identified more than 45 potential biomarkers of OTS. In the present study, we hypothesized that combinations of these biomarkers could be an accurate diagnostic tool for OTS.

MethodsWe selected parameters with largest difference and fewest overlapping results compared to healthy athletes and highest feasibility and reproducibility. Among the multiple combinations attempted, we chose those that did not show overlapping results, according to the objective.

ResultsWe included 11 clinical parameters, 4 basal hormones, and 5 hormonal responses in Insulin Tolerance Test (ITT). The three selected diagnostic tools were the (i) EROS-CLINICAL, with only clinical parameters, which was suitable as an initial assessment for athletes suspected of OTS; (ii) EROS-SIMPLIFIED, with clinical parameters and basal hormones, when the EROS-CLINICAL was inconclusive; and (iii) EROS-COMPLETE, with basal and hormonal responses to stimulation tests, which was valuable for population-based screening, research purposes, and unusual presentations of OTS.

ConclusionWe identified innovative tools with 100% accuracy for the diagnosis of OTS, without the need to exclude confounding disorders.

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INSUFFICIENT EATING AND BAD SLEEP ARE THE NOVEL TRIGGERS OF OVERTRAINING SYNDROME

 

Eating and sleeping patterns as triggers of Overtraining Syndrome

INSUFFICIENT CALORIC INTAKE AND SLEEP QUALITY AS NOVEL TRIGGERS OF OTS AND NOVEL CONSEQUENCES OF OTS 

This is a post-hoc analysis of all the arms of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study that evaluated whether and which are the novel triggers of overtraining syndrome (OTS) besides excessive training, the only recognized trigger of OTS to date, and potential novel consequences of OTS.

We detected that insufficient protein intake alone, insufficient carbohydrate intake alone, or insufficient overall caloric intake may trigger OTS even when training is not excessive, and is enhanced by bad sleep quality.

We also discovered that OTS by itself may cause multiple consequences. OTS causes the interruption of the prolonged hormonal response that typically occurs in athletes and that help increase the time-to-fatigue, leading to reduction of the time until fatigue and consequently decreased performance in long-duration sports. OTS reduces the testosterone:estradiol (T:E) probably by enhancing the aromatase enzyme activity pathologically, similarly to what happens in obesity, type 2 diabetes, and other metabolic and inflammatory chronic diseases, increases body fat, decreases muscle mass, reduces metabolic rate, fat oxidation, and level of hydration, decreases levels of vigor, and increases tension and fatigue levels.

The worsening of body composition and metabolism, the decreased motivation, the decreased T:E ratio and the impaired hormonal responses to stimulation altogether may justify the paradoxical decrease of sports performance, the hallmark of OTS. 

Links:

https://pubmed.ncbi.nlm.nih.gov/31548891/

 https://bmcsportsscimedrehabil.biomedcentral.com/articles/10.1186/s13102-019-0132-x

Reference:

Cadegiani FA, Kater CE. Novel causes and consequences of overtraining syndrome: the EROS-DISRUPTORS study. BMC Sports Sci Med Rehabil. 2019 Sep 18;11:21. doi: 10.1186/s13102-019-0132-x. 

 

Study Abstract

Abstract

Background: Hormonal physiology in athletes, dysfunctional paths leading to overtraining syndrome (OTS), and clinical and biochemical behaviors that are independently modified by the presence of OTS remain unclear. Although multiple markers of OTS have recently been identified, the independent influence of OTS on hormones and metabolism have not been assessed. Hence, the objective of the present study was to uncover the previously unrecognized independent predictors of OTS and understand how OTS independently modifies the behaviors of clinical and biochemical parameters.

Methods: In a total of 39 athletes (OTS-affected athletes (OTS) = 14 and healthy athletes (ATL) = 25), we performed two clusters of statistical analyses using the full data of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study, in a total of 117 markers. We first used logistic regression to analyze five modifiable parameters (carbohydrate, protein, and overall caloric intake, sleep quality, and concurrent cognitive effort) as potential additional independent risk factors for OTS, and OTS as the outcome. We then used multivariate linear regression to analyze OTS as the independent variable and 38 dependent variables. Training patterns were found to be similar between OTS and ATL, and therefore excessive training was not a risk, and consequently not a predictor, for OTS.

Results: Each of the three dietary patterns (daily carbohydrate, daily protein, and daily overall calorie intake) were found to be the independent triggers of OTS, while sleeping, social, and training characteristics depended on other factors to induce OTS. Once triggered, OTS independently induced multiple changes, including reductions of cortisol, late growth hormone and adrenocorticotropic hormone responses to stimulations, testosterone-to-estradiol ratio, neutrophils, neutrophil-to-lymphocyte ratio, vigor levels, hydration status, and muscle mass, while increase of tension levels and visceral fat.

Conclusions: OTS can be independently triggered by eating patterns, regardless of training patterns, while the occurrence of OTS reduced late hormonal responses and the testosterone-to-estradiol ratio, worsened mood, and affected the immunology panel. These novel findings may explain underperformance, which is the key characteristic of OTS.

 

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OVERTRAINING SYNDROME BEYOND OVERTRAINING 

 

Novel markers and mechanisms on Overtraining Syndrome

THE EROS STUDY DISCOVER NOVEL MARKERS AND MECHANISMS OF OVERTRAINING SYNDROME 

The present study is an overall analysis of all the markers and subjects evaluated by the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study. We had the surprising discovery that the majority of the markers evaluated in athletes affected by overtraining syndrome were neither abnormal nor normal, because when these markers were analyzed through the perspective of the usual reference ranges and healthy sedentary, levels found in OTS-affected athletes were similar. However, when compared to healthy athletes, these markers were different between them. It occurred because several markers were unexpectedly different between healthy athletes and healthy sedentary, which was demonstrated to be physiological endocrine and metabolic adaptations that occur in athletes that had not been described until our study. Considering this, abnormalities in OTS are not overt, but relative instead, since these markers are altered to what would be expected for athletes, but normal if we consider the typical reference ranges.

We also found OTS can occur independently from excessive training, since insufficient calorie, protein, or carbohydrate intake, poor sleep quality, or concurrent excessive cognitive effort were the found to be triggers of OTS, without the need of excessive training for its trigger.

Overall, multiple biochemical and hormonal conditioning processes occur in athletes, which are lost in OTS. OTS results from a mix of losses of conditioning processes, which we termed as 'mix of deconditioning processes'.

The understanding of OTS as a combination of ‘deconditioning processes’ helped to elucidate the underlying reason of the unexplained decrease in performance, the hallmark of OTS.

Since the loss of sports performance was paradoxical to the expected, since we would expect that performance would improve progressively, we found sufficient data to suggest that OTS would be more precisely named as “Paradoxical Deconditioning Syndrome (PDS)”, since PDS seems to be a more appropriate and descriptive name for OTS than the previous misnomer (‘overtraining’).

The EROS study also unveiled the existence of multiple independent metabolic and hormonal adaptations to exercise, in addition to those in cardiovascular, autonomic, and neuromuscular systems. This serendipitous finding may explain some of the health benefits and progressive improvement observed in athletes.

The present analysis is a synthesis of the novel perspective on OTS that the EROS study brought, and helped changed and improved the understanding of the mechanisms of the pathophysiology of OTS, its biomarkers, triggers, and consequences. 

Links:

https://bmjopensem.bmj.com/content/5/1/e000542

https://pubmed.ncbi.nlm.nih.gov/31297238/

Reference:

Cadegiani FA, Kater CE. Novel insights of overtraining syndrome discovered from the EROS study. BMJ Open Sport Exerc Med. 2019 Jun 20;5(1):e000542. doi: 10.1136/bmjsem-2019-000542.  

 

Study abstract

Abstract

Background: Excessive training and inadequate recovery could cause 'overtraining syndrome' (OTS), which is characterised by underperformance and fatigue. The pathophysiology of OTS is unclear. We aimed to describe novel mechanisms and risk factors associated with OTS, and thereby facilitate its early identification and prevention, from a comprehensive joint qualitative analysis of the findings from all the four arms of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study.

Methods: We compared the types and proportions of behavioural patterns of 67 evaluated parameters of OTS from 51 participants-athletes with OTS (OTS, n=14), healthy athletes (n=25) and healthy non-physically active controls (n=12). We performed overall and pairwise comparisons for statistically significant differences between the three groups (p<0.05).

Results: A total of 44 (65.7%) markers exhibited significant differences between the three groups: 32 (72.7%) showed a loss of the conditioning effect of exercise ('deconditioning'), 7 (15.9%) showed changes exclusive to OTS, 3 (6.8%) maintained the exercise-induced conditioning effects and 2 (4.5%) revealed an exacerbation of the adaptive changes to exercises.

Conclusion: Our findings suggest that OTS is likely triggered by multiple factors, not restricted to excessive training, resulted from a chronic energy deprivation, leading to multiple losses in the conditioning processes typically observed in healthy athletes, as a combination of 'paradoxical deconditioning' processes, which explains the gradual and marked loss of physical conditioning found in OTS. We, therefore, suggest that the term 'paradoxical deconditioning syndrome' better represents the features of this syndrome.

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CROSSFIT AND RELATED SPORTS: A UNIQUE CONDITIONING LEVEL 

 

Specific metabolic and endocrine patterns in High-Intensity Functional Training (HIFT)

CROSSFIT AND OTHER HIGH-INTENSITY FUNCTIONAL TRAINING (HIFT) MODALITIES LEAD TO MORE PROMINENT HORMONAL AND METABOLIC ADAPTATIONS THAN OTHER SPORTS, AND WHEN OVERTRAINING SYNDROME OCCURS IN THESE SPORTS, IT TENDS TO BE MILDER WITH POORER MARKERS, AND THEREFORE HARDER TO DIAGNOSE 

CrossFit and other high-intensity functional training (HIFT) sports is a modality with unique characteristic of mixing different abilities and dimensions of the physical conditioning, requiring explosive, strength, stop-and-go, explosive, anaerobic, and aerobic abilities altogether within a single sport.

In the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study, a subpopulation of athletes practiced HIFT, and were compared to all athletes and to non-HIFT athletes.

Athletes that practiced HIFT presented enhanced hormonal and metabolic conditioning processes compared to non-HIFT athletes.

HIFT athletes that developed overtraining syndrome (OTS) presented fewer and milder symptoms that OTS-affected athletes from other modalities, as well as fewer biochemical and body composition and metabolism abnormalities. In addition, low carbohydrate and low overall caloric intake were the main triggers of OTS in HIFT-athletes.

The peculiarities of HIFT sports in terms of the combination of different abilities joined in a single sport reflect in the differences in the level of hormonal and metabolic conditioning processes, as well as in the characteristics of OTS in this sports modality. 

Links:

https://www.tandfonline.com/doi/full/10.1080/02640414.2018.1555912

https://pubmed.ncbi.nlm.nih.gov/30786846/ 

Reference:

Cadegiani FA, Kater CE, Gazola M. Clinical and biochemical characteristics of high-intensity functional training (HIFT) and overtraining syndrome: findings from the EROS study (The EROS-HIFT). J Sports Sci. 2019 Feb 20:1-12. doi: 10.1080/02640414.2018.1555912. 

 

Study abstract:

Abstract

The metabolic and hormonal consequences of high-intensity functional training regimens such as CrossFit® (CF) are unclear. Little is known about the triggers and clinical and biochemical features of CF-related overtraining syndrome (OTS). The EROS study compared endocrine and metabolic responses, and eating, social, psychological and body characteristics of OTS-affected (OTS) and healthy athletes (ATL), and non-physically active controls (NPAC). The current study is a post-hoc analysis of the CF subgroups of the EROS study, to evaluate specific characteristics of CF in ATL and OTS. Parameters were overall and pairwise compared among OTS-affected (CF-OTS) and healthy (CF-ATL) athletes that exclusively practiced CF, and NPAC. CF-ATL yielded earlier and enhanced cortisol, GH, and prolactin responses to an insulin tolerance test (ITT), increased neutrophils, lower lactate, increased testosterone, improved sleep quality, better psychological performance, increased measured-to-predicted basal metabolic rate (BMR) ratio and fat oxidation, and better hydration, when compared to NPAC. Conversely, more than 90% of the adaptive changes in CF were lost under OTS, including an attenuation of the hormonal responses to an ITT, increased estradiol, decreased testosterone, and decreased BMR and fat oxidation; the most remarkable trigger of OTS among "HIFT athletes" was the long-term low carbohydrate and calorie intake.

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INSUFFICIENCIES, NOT EXCESSES, LEAD TO OVERTRAINING SYNDROME 

 

Triggers and consequences of Overtraining Syndrome

INSUFFICIENT FOOD, INSUFFICIENT SLEEP, AND INSUFFICIENT REST WERE FOUND TO BE TRIGGERS OF OVERTRAINING SYNDROME, AND OVERTRAINING SYNDROME CAUSES INCREASE OF BODY FAT, AND DECREASE OF MUSCLE MASS, FAT BURNING, HYDRATION, AND MOOD STATES.

The present study is the arm of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study that evaluated body composition, metabolism, sleep, psychological and eating patterns of overtraining and healthy athletes, and healthy sedentary subjects.

We found out that athletes affected by OTS had significantly worse sleep quality, worked or studied for longer periods of time, ate fewer calories, less protein, and less carbohydrate, had decreased libido, worse mood states, decreased basal metabolic rate, decrease fat burning, increased body fat, decreased muscle mass, and were less hydrated than healthy athletes. When compared to sedentary, OTS-affected athletes had similar levels of almost all markers, except for lower libido, lower vigour, and increased fatigue, compared to sedentary. 

Overtraining syndrome demonstrated to be a combination of multiple abnormalities in body composition and metabolism, and psychological states, and presented differences in terms of habits, since OTS-affected athletes had worse sleep quality, had more cognitive demands, and ate less calories, protein, and carbohydrate, than healthy athletes. 

Links:

https://www.tandfonline.com/doi/full/10.1080/02640414.2018.1424498

https://pubmed.ncbi.nlm.nih.gov/29313445/ 

Reference:

Cadegiani FA, Kater CE. Body composition, metabolism, sleep, psychological and eating patterns of overtraining syndrome: results of the EROS study (EROS-PROFILE). J Sports Sci. 2018 Aug;36(16):1902-1910. doi: 10.1080/02640414.2018.1424498. PMID: 29313445.  

 

Study abstract

Overtraining syndrome (OTS) is caused by an imbalance between training, nutrition and resting, and leads to decreased performance and fatigue; however, the precise underlying triggers of OTS remain unclear. This study investigated the body composition, metabolism, eating, sleeping patterns and mood states among participants with OTS. Selected participants were divided into OTS-affected athletes (OTS, n = 14), healthy athletes (ATL, n = 25), and healthy non-physically active controls (NCS, n = 12). Compared to ATL, OTS showed decreased sleep quality (p = 0.004); increased duration of work or study (p < 0.001); decreased libido (p = 0.024); decreased calorie (p < 0.001), carbohydrate (p < 0.001) and protein (p < 0.001) intakes; decreased mood states (p < 0.001); decreased basal metabolic rate (p = 0.013) and fat burning (p < 0.001); increased body fat (p = 0.006); decreased muscle mass (p = 0.008); and decreased hydration (p < 0.001). Levels were similar between OTS and NCS, except for worsened fatigue (p < 0.001) and vigour (p = 0.001) in OTS. Reduced calorie intake, worsened sleep, and increased cognitive activity are likely OTS triggers. OTS appears to induce dehydration, increase body fat, decrease libido, and worsen mood.

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IT’S ALL ABOUT HORMONES, BUDDY 

Basal hormones and Overtraining Syndrome 

 

NOT ONLY WHEN HORMONES ARE EVALUATED UNDER STIMULATIONS THAT OVERTRAINED ATHLETES CAN BE DETECTED. EASIER ANALYSIS OF BASAL RESTING HORMONAL LEVELS MAY ALSO ALLOW TO DETECT MARKERS OF OVERTRAINING SYNDROME (OTS).

The present analysis is the arm of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study that evaluated hormonal, inflammatory, immunologic, and muscular basal markers in athletes affected by OTS, healthy athletes, and healthy sedentary subjects. All groups were sex-, age-, and body mass index (BMI)-matched.

Healthy athletes demonstrated higher testosterone levels, increased neutrophil:lymphocyte ratio, paradoxical decreased lactate levels, and increased nocturnal urinary catecholamines (NUC). These are likely among the multiple hormonal, metabolic, muscular, and immunologic conditioning processes that athletes undergo along with progressive increase of training volume, intensity, and load.

Increased neutrophil:lymphocyte ratio is typically a marker of worse prognosis in acute severe states. However, physiologically, it may be an adaptive process in athletes to provide further immunologic support, since these athletes do not present reduction of lymphocytes.

Decreased lactate was another unexpected finding in healthy athletes since it increases with training, although the blood exams were collected 48 hours after the last training session. Possibly, increased lactate clearance may occur, what is typically called as “faster muscle recovery”.

When affected by OTS, athletes experiment a loss of many of these adaptive processes, an exacerbation of NUC, and disproportionally increased muscular parameters. Increased lactate and CK levels help explain why overtrained athletes tend to complain of “prolonged and impaired muscle recovery”. Exacerbated NUC may reflect an attempt to keep body functioning under the dysfunctional state of OTS.

A remarkable finding was the pathological reduction of the testosterone:estradiol (T:E) ratio, reduced by 50% when compared to both healthy athletes and healthy sedentary. It means that reduced T:E ratio is an overt abnormality, specific of OTS when detected in athletes. Reduction of the T:E ratio may also be found in obesity, diabetes, and other metabolic and inflammatory diseases. It occurs likely as a result of a pathological exacerbation of aromatase activity, which is the enzyme that converts testosterone into estradiol. Unlike when estradiol raises in consequence of increase of testosterone, that leads to benefits including increase of muscle and bone mass, libido, and energy levels, but when the T:E proportion is maintained, in the case of increase of estradiol due to enhanced aromatase activity leads to reduction of testosterone and consequently reduction of the T:E ratio.

As seen above, multiple basal markers also allow help to diagnose of athletes suspected of OTS. And we also learned that exercise may lead to more benefits than previously thought. 

Links:

https://meridian.allenpress.com/jat/article/54/8/906/420847/Basal-Hormones-and-Biochemical-Markers-as

https://pubmed.ncbi.nlm.nih.gov/31386577/ 

Reference:

Cadegiani FA, Kater CE. Basal Hormones and Biochemical Markers as Predictors of Overtraining Syndrome in Male Athletes: The EROS-BASAL Study. J Athl Train. 2019 Aug;54(8):906-914. doi: 10.4085/1062-6050-148-18.  

 

Study abstract

Abstract

Context: Overtraining syndrome (OTS) and related conditions cause decreased training performance and fatigue through an imbalance among training volume, nutrition, and recovery time. No definitive biochemical markers of OTS currently exist.

Objective: To compare muscular, hormonal, and inflammatory parameters among OTS-affected athletes, healthy athletes, and sedentary controls.

Design: Cross-sectional study.

Setting: Laboratory.

Patients or other participants: Fifty-one men aged 18 to 50 years (14 OTS-affected athletes [OTS group], 25 healthy athletes [ATL group], and 12 healthy sedentary participants [NCS group]), with a body mass index of 20 to 30.0 kg/m2(sedentary) or 20 to 33.0 kg/m2(athletes), recruited through social media. All 39 athletes performed both endurance and resistance sports.

Main outcome measure(s): We measured total testosterone, estradiol, insulin-like growth factor 1, thyroid-stimulating hormone, free thyronine, total and fractioned catecholamines and metanephrines, lactate, ferritin, creatinine, creatine kinase, erythrocyte sedimentation rate, C-reactive protein, lipid profile, hemogram, and testosterone : estradiol, testosterone : cortisol, neutrophil : lymphocyte, platelet: lymphocyte, and catecholamine : metanephrine ratios. Each parameter was statistically analyzed through 3-group comparisons, and wheneverP< .05, pairwise comparisons were performed (OTS × ATL, OTS × NCS, and ATL × NCS).

Results: Neutrophils and testosterone were lower in the OTS group than in the ATL group but similar between the OTS and NCS groups. Creatine kinase, lactate, estradiol, total catecholamines, and dopamine were higher in the OTS group than in the ATL and NCS groups, whereas the testosterone : estradiol ratio was lower, even after adjusting for all variables. Lymphocytes were lower in the ATL group than in the OTS and NCS groups. The ATL and OTS groups trained with the same intensity, frequency, and types of exercise.

Conclusions: At least in males, OTS was typified by increased estradiol, decreased testosterone, overreaction of muscle tissue to physical exertion, and immune system changes, with deconditioning effects of the adaptive changes observed in healthy athletes.

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A SORT OF RELATIVE ADRENAL INSUFFICIENCY HAPPENS IN OVERTRAINING SYNDROME 

 

Cortisol and Overtraining Syndrome

OVERTRAINING SYNDROME LEADS TO REDUCTION OF CORTISOL RELEASE IN RESPONSE TO STIMULATIONS AND IMPAIRED CORTISOL RESPONSE TO AWAKENING 

The EROS-HPA axis arm of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study evaluated the hypothalamus-pituitary-adrenal (HPA) axis at all level, by directly stimulating the adrenal gland and by stimulation the whole HPA axis through an insulin tolerance test (ITT), that causes a stressful environment by causing hypoglycemia.

All groups, of athletes affected by overtraining syndrome, healthy athletes, and healthy sedentary, had similar direct adrenal responses to a stimulation with synthetic ACTH, showing that neither healthy athletes disclose direct adrenal enhancement, nor OTS-affected athletes had impaired adrenal responses.

Conversely, when the whole HPA axis is stimulated through an ITT, the pituitary hormone that stimulates cortisol, called adrenocorticotropic hormone (ACTH), and the cortisol are released in sequence, aiming to counterbalance the hypoglycemic state, since cortisol is an insulin counter-regulator, i.e., a hormone that induces hyperglycemia. The ITT is a type of stimulation test that stimulates the hypothalamus directly, without interference from other systems, and can tell about the hypothalamic-pituitary axes precisely.

Healthy athletes demonstrated prompter, enhanced, and prolonged ACTH and cortisol response than healthy sedentary. Considering that this stimulation is independent of exercise, any physical effort, and also independent of cardiovascular, musculoskeletal or any other system, these differences provide sufficient substantiation to conclude that HPA axis responses to stimulations are optimized in athletes, regardless of physical activity. 

Links:

https://sportsmedicine-open.springeropen.com/articles/10.1186/s40798-017-0113-0

https://pubmed.ncbi.nlm.nih.gov/29222606/ 

Reference:

Cadegiani FA, Kater CE. Hypothalamic-pituitary-adrenal (HPA) axis functioning in overtraining syndrome: findings from Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) - EROS-HPA axis. Sports Med Open. 2017 Dec 8;3(1):45. DOI: 10.1186/s40798-017-0113-0. PMID: 29222606. 

 

Study abstract

Background

Overtraining syndrome (OTS) results from excessive training load without adequate recovery and leads to decreased performance and fatigue. The pathophysiology of OTS in athletes is not fully understood, which makes accurate diagnosis difficult. Previous studies indicate that alterations in the hypothalamus-pituitary-adrenal (HPA) axis may be responsible for OTS; however, the data is not conclusive. This study aimed to compare, through gold standard and exercise-independent tests, the response of the HPA axis in OTS-affected athletes (OTS group) to healthy physically active subjects (ATL group) and healthy non-active subjects (NCS group).

Methods

Selected subjects were evaluated for cortisol response to a 250-μg cosyntropin stimulation test (CST), cortisol and adrenocorticotropic hormone (ACTH) responses during an insulin tolerance test (ITT), and salivary cortisol rhythm (SCR).

Results

A total of 51 subjects were included (OTS, n = 14; ATL, n = 25; and NCS, n = 12). Cortisol response in the CST was similar among the three groups. Conversely, mean cortisol response during an ITT was significantly higher in ATL (21.7 μg/dL; increase = 9.2 μg/dL) compared to OTS (17.9 μg/dL; 6.3 μg/dL) and NCS (16.9 μg/dL; 6.0 μg/dL) (p ≤ 0.001; p = 0.01). Likewise, median ACTH response during an ITT was significantly higher in ATL (91.4 pg/mL; increase = 45.1 pg/mL) compared to OTS (30.3 pg/mL; 9.7 pg/mL) and NCS (51.4 pg/mL; 38.0 pg/mL) (p = 0.006; p = 0.004). For SCR, mean cortisol 30 min after awakening was significantly higher in ATL (500 ng/dL) compared to OTS (323 ng/dL) and NCS (393 ng/dL) (p = 0.004). We identified the following cutoffs that could help exclude or confirm OTS: cortisol level at 30 min after awakening (exclusion = > 530 ng/dL); cortisol response to ITT (exclusion = > 20.5 μg/dL; confirmation = < 17 μg/dL or increase < 9.5 μg/dL); and ACTH response (exclusion = > 106 pg/mL or increase > 70 pg/mL; confirmation = < 35 pg/mL and increase < 14.5 pg/mL).

Conclusion

The findings of the present study showed that healthy athletes disclose adaptions to exercises that helped improve sport-specific performance, whereas this sort of hormonal conditioning was at least partially lost in OTS, which may explain the decrease in performance in OTS.

Key-points

  • The hypothalamus-pituitary-adrenal (HPA) axis response to ITT are exacerbated in healthy athletes, compared to sedentary healthy subjects. ITT may be a tool to evaluate whether the athlete is well-conditioned and to predict performance, once the exacerbation of the HPA axis responses may play an important role in the progressive improvement in sports performance.
  • There are intrinsic dysfunctions of the HPA axis response to a stress situation in OTS-affected athletes, compared to healthy athletes, in an independent way from exercise-induced stimulation; the dysfunctions of the HPA axis are located in the hypothalamus and the pituitary, and not the adrenals. In case an athlete is suspected for OTS, an ITT stimulation test may be performed. In the absence of confounding diseases, blunted cortisol and ACTH responses most likely confirm the diagnosis of OTS, with accurate cutoffs.
  • Two new concepts were unprecedentedly demonstrated by the study. The first new concept is that physical activity, at least moderate-to-intense, elicits conditioning effects of hormonal responses to stimulation that goes beyond exercise, which we called as “hormonal conditioning of the athlete”. Besides helping explain the improvement in the sports performance, the novel conditioning process found by our study may be the missing link for the understanding of the underlying mechanisms of the improvement observed in several responses to harmful situations, such as infections, neoplasms, traumas, inflammations, and psychiatric conditions that are observed in athletes, and which were not fully understood so far. The second concept is that whereas healthy athletes seem to present hormonal conditioning adaptions, those affected by overtraining seem to have impaired or maladapted hormonal conditioning, as over-trained athletes have a blunted optimized hormone response to stress that seem to be acquired by athletes; as a sort of deconditioning process, which indicates that the decreased performance and the reduced time-to-fatigue observed during OTS; these two key features of OTS, not yet fully understood, may be at least partly explained by the present findings.

Despite these unprecedented findings, further studies are recommended to confirm our results.

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WHAT HAPPENS TO HORMONES IN HEALTHY AND IN OVERTRAINED ATHLETES? 

 

Hormonal responses to stress in healthy and overtraining athletes

HORMONES ARE OPTIMIZED IN HEALTHY ATHLETES, WHEREAS BLUNTED IN OVERTRAINING SYNDROME 

The EROS-STRESS arm of the Endocrine and metabolic Responses on Overtraining Syndrome (EROS) study evaluated the hormonal responses to a non-exercise, direct stimulation test to the hypothalamic-pituitary axes, except for cortisol and ACTH, which have been described in the EROS-HPA axis arm. The EROS-STRESS arm also described the symptoms of hypoglycemia experimented during the stimulation test, which was an Insulin Tolerance Test (ITT).

Surprisingly, we detected increased basal GH in healthy athletes compared to healthy sedentary, while it was blunted in athletes affected by overtraining syndrome (OTS). This is surprising because GH is released in peaks for a few minutes but remains undetectable the majority of the time, particularly in males. Even adjusting by the removal of outliers, which in this case were those that collected blood during a GH peak, differences remained significantly. Whether there is any role of the detectable, instead of indetectable, basal GH in athletes is unknown.

Likewise, basal prolactin was also higher in healthy athletes compared to sedentary, but lower in OTS-affected athletes compared to healthy athletes. Both basal hormones were similar between OTS and sedentary.

In response to the stimulation test, GH reached a peak approximately 04 times higher in healthy athletes than both overtrained athletes and healthy sedentary. GH was also released more promptly and the peak remained for longer periods of time in healthy athletes. It means that healthy athletes are conditioned to release GH more quickly, at higher levels, and to keep releasing for longer, even when stimulation does not come from exercise or from cardiovascular or musculoskeletal systems. All these characteristics seem to be lost in OTS.

Healthy athletes were the only group that experimented a significant increase of prolactin in response to an ITT. The groups of OTS-affected athletes and sedentary did not present any significant prolactin release. Since prolactin release is associated with improvement of stress responses, this may be an additional beneficial conditioning process that athletes undergo, and which is also lost in OTS.

Hypoglycemia leads to two types of symptoms: those derived from hyperadrenergic release and symptoms resulted from neuroglycopenia. Interestingly, overtrained athletes had fewer adrenergic symptoms, already adjusted for glucose levels. The loss of adrenergic symptoms usually occurs in patients affected by type 1 or 2 diabetes that present several episodes of hypoglycemia or remain under hypoglycemia for long periods of time. Their body gets kind of ‘used’ to hypoglycemia and lose sensitivity to adrenergic release, leading to fewer and milder symptoms. Possibly, athletes affected by OTS may train or spend more time under unnoticed hypoglycemia, which makes sense when we consider that their hormonal responses to simulation are weaker than expected, and they usually train in an intensity that surpasses the ability of the body to generate glucose from ammino acids and lipids (a process called gluconeogenesis), associated with depleted storage of glycogen, which is also typically found in OTS. 

The study shows that athletes affected by OTS present similar patterns of the sedentary, as a sort of regression of their improvement, which matches with the regression in terms of physical performance. 

Links:

https://www.jsams.org/article/S1440-2440(17)31746-2/fulltext

https://pubmed.ncbi.nlm.nih.gov/29157780/ 

Reference:

Cadegiani FA, Kater CE. Hormonal responses to a non-exercise stress test in athletes with overtraining syndrome: results from the Endocrine and metabolic Responses on Overtraining Syndrome (EROS) - EROS-STRESS. J Sci Med Sport. 2018 Jul;21(7):648-653. DOI: 10.1016/j.jsams.2017.10.033. PMID: 29157780.  

 

Study abstract

Objectives: Overtraining syndrome (OTS) leads to worsened sports performance and fatigue. The pathophysiology of OTS has not been entirely elucidated, and there is a lack of accurate markers for its diagnosis. Changes in hormonal responses implicated in OTS were stimulated by exercise, which has limited their interpretation. Hence, we aimed to evaluate growth hormone (GH) and prolactin responses to a gold-standard and exercise-independent stimulation test, the insulin tolerance test (ITT).

Design: Volunteers were recruited and divided into OTS-affected athletes (OTS), healthy athletes (ATL), and healthy non-active subjects (NCS) groups, after general and specific inclusion and exclusion criteria.

Methods: We evaluated the responses of growth hormone (GH) and prolactin to the ITT, and compared between groups.

Results: A total of 51 subjects were included (OTS, n=14, ATL, n=25, and NCS, n=12). OTS disclosed significantly lower basal levels of GH (p=0.003) and prolactin (p=0.048), and GH (p=0.001) and prolactin (p<0.001) responses to ITT (p=0.001), compared to ATL, but similar to NCS. OTS showed a later rise in GH levels in response to hypoglycemia, compared to ATL, but not to NCS. We suggest cutoffs for GH and prolactin levels to aid in the diagnosis of OTS.

Conclusions: OTS-affected athletes show reduced GH and prolactin basal levels and responses to a non-exercise stress test compared to healthy athletes, but not to sedentary subjects.

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THE SYSTEMATIC REVIEW THAT LED TO THE EROS STUDY 

 

Systematic review of the hormonal aspects of Overtraining Syndrome

STIMULATED, RATHER THAN BASAL HORMONES, WERE BETTER INDICATORS OF OVERTRAINING SYNDROME, ACCORDING TO A SYSTEMATIC REVIEW PRIOR TO THE EROS STUDY

We conducted a systematic review on the hormonal characteristics of athletes affected by overtraining syndrome (OTS). From hundreds of articles, 38 were included after the selection criteria.

Basically, the vast majority measured athletes that were not in actual overtraining, but in a forced state of overreaching instead. Both overreaching and overtraining leads to fatigue and decreased performance, but overreaching is an acute reaction and is rapidly recovered, while overtraining is a long-term, not easily recoverable, that also presents psychological aspects.

Also, athletes were from a wide variety of sports, levels of conditioning, and assessment methods were highly heterogeneous.

Basal hormones were shown to be similar between healthy and OTS-affected athletes, while stimulated GH and ACTH tended to be blunted in OTS. Other hormonal findings were conflicting.

Another message from the systematic review is the urgent need for standardization and uniformization for the evaluation methods for hormones, in order to allow further direct comparisons and metanalysis.

Links:

https://bmcsportsscimedrehabil.biomedcentral.com/articles/10.1186/s13102-017-0079-8

https://pubmed.ncbi.nlm.nih.gov/28785411/ 

Reference:

Cadegiani FA, Kater CE. Hormonal aspects of overtraining syndrome: a systematic review. BMC Sports Sci Med Rehabil. 2017 Aug 2;9:14. DOI: https://doi.org/10.1186/s13102-017-0079-8 PMID: 28785411. 

 

Study abstract

Background: Overtraining syndrome (OTS), functional (FOR) and non-functional overreaching (NFOR) are conditions diagnosed in athletes with decreased performance and fatigue, triggered by metabolic, immune, hormonal and other dysfunctions and resulted from an imbalance between training stress and proper recovery. Despite previous descriptions, there is a lack of a review that discloses all hormonal findings in OTS/FOR/NFOR. The aim of this systematic review is to evaluate whether and which roles hormones play in OTS/FOR/NFOR.

Methods: A systematic search up to June 15th, 2017 was performed in the PUBMED, MEDLINE and Cochrane databases following PRISMA protocol, with the expressions: (1)overtraining, (2)overreaching, (3)overtrained, (4)overreached, or (5)underperformance, and (plus) (a)hormone, (b)hormonal, (c)endocrine, (d)adrenal, (e)cortisol, (f)GH, (g)ACTH, (h)testosterone, (i)IGF-1, (j)TSH, (k)T4, (l)T3, (m)LH, (n)FSH, (o)prolactin, (p) IGFBP-3 and related articles.

Results: A total of 38 studies were selected. Basal levels of hormones were mostly normal in athletes with OTS/FOR/NFOR compared with healthy athletes. Distinctly, stimulation tests, mainly performed in maximal exercise conditions, showed blunted GH and ACTH responses in OTS/FOR/NFOR athletes, whereas cortisol and plasma catecholamines showed conflicting findings and the other hormones responded normally.

Conclusion: Basal hormone levels are not good predictor but blunted ACTH and GH responses to stimulation tests may be good predictors of OTS/FOR/NFOR.

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ATHLETES CAN NOW KNOW WHEN THEY ARE IMPROVING FROM OVERTRAINING SYNDROME

This is the study presented at The Endocrine Society meeting in 2020 where we published the parameters of recovery from Overtraining Syndrome (OTS) found in the longitudinal follow-up of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study. This study had its full content further published in another journal in the beginning of 2021.

We showed that markers of recovery include increase of early cortisol and early and late GH response to stimulation, increase in the testosterone:estradiol ratio, freeT3, IGF-1, and cortisol awakening response (CAR).

In common, these are markers that can also be observed during the recovery process of other chronic diseases, including metabolic and inflammatory ones, which reinforces the multifactorial and complex pathophysiology of OTS.

Cadegiani F, da Silva PLH, Abrao TPC, Kater CE. Novel Hormonal and Metabolic Markers of Recovery From Overtraining Syndrome Unveiled by the Longitudinal ARM of the Eros Study - the Eros-Longitudinal Study.J Endocr Soc. 2020;4(Suppl 1):SAT-LB4. Published 2020 May 8. doi:10.1210/jendso/bvaa046.2337.

Links:
https://academic.oup.com/jes/article/4/Supplement_1/SAT-LB4/5834033
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7208838/

Abstract

Background: Overtraining Syndrome (OTS) is an unexplained underperformance syndrome triggered by excessive training, insufficient caloric intake, inadequate sleep, and excessive cognitive and social demands. Investigations of markers of the challenging recovery from OTS have not been reported to date. The objective of the present study is to describe novel markers, and biochemical and clinical behaviors during the restoration process of OTS.Design: A 12-week interventional protocol in 12 athletes affected by OTS was conducted, including increased food intake, transitory interruption of the trainings, improvement of sleep quality, and management of stress.Methods: We assessed 50 parameters, including hormonal responses to an insulin tolerance test (ITT), basal hormonal and non-hormonal biochemical markers, body metabolism and composition. Results: In response to an ITT, early cortisol (p = 0.026), early GH (p = 0.004), and late GH (p = 0.037) improved significantly. Basal estradiol (p = 0.0002) and nocturnal urinary catecholamines, (p = 0.043) reduced, while testosterone (p = 0.014), testosterone:estradiol (T:E) ratio (p = 0.0005), freeT3 (p = 0.043), IGF-1 (p = 0.003), and cortisol awakening response (CAR) (p = 0.001) increased significantly. All basal parameters and early responses to ITT normalized, when compared to healthy athletes. Basal metabolic rate, fat oxidation, body fat, muscle mass, and hydration status had partial but non-significant improvements. Conclusion: After 12 weeks, athletes affected by actual OTS demonstrated substantial improvements, remarkably IGF-1, freeT3, CAR, testosterone, estradiol testosterone:estradiol ratio, CK and catecholamines, and early cortisol, early prolactin, and overall GH responses to stimulations.

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How “The Cortisol Awakes” Tells About Health Status in Athletes


June 27, 2021

Cortisol releasing patterns after awakening in athletes

THE CORTISOL RESPONSE TO AWAKENING IS IMPAIRED IN ATHELTES AFFECTED BY OVERTRAINING SYNDROME 

This is a post-hoc analysis of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study that compared the Cortisol Awakening Response (CAR) between athletes affected by overtraining syndrome (OTS) and healthy athletes. CAR is a physiological cortisol response that occurs when we wake up. Cortisol levels rise between 30% and 70% between the moment that we open our eyes and 30 minutes after awakening. The study not only compared the salivary cortisol at awakening and 30 minutes after, but also at 4PM and 11PM, in order to determine the salivary cortisol rhythm. We found that athletes with OTS presented a flawed CAR comparing to healthy athletes, which may help explain why OTS-affected athletes typically complain of lack of energy when they wake up, besides the overall reduction in energy levels. Conversely, the cortisol loop during the day until the night was not affected by OTS. 

Links:

https://journals.humankinetics.com/view/journals/ijspp/aop/article-10.1123-ijspp.2020-0205/article-10.1123-ijspp.2020-0205.xml

https://pubmed.ncbi.nlm.nih.gov/33662935/ 

Reference:

Anderson T, Wideman L, Cadegiani FA, Kater CE. Effects of Overtraining Status on the Cortisol Awakening Response-Endocrine and Metabolic Responses on Overtraining Syndrome (EROS-CAR). Int J Sports Physiol Perform. 2021 Mar 3:1-9. doi: 10.1123/ijspp.2020-0205. Epub ahead of print. PMID: 33662935. 

ABSTRACT 

Introduction: The cortisol awakening response (CAR) is a distinct component of the circadian cortisol profile and has promise as a biomarker for the monitoring of athlete readiness and training status. Although some studies have suggested the CAR may be affected by the development of overtraining syndrome (OTS), this has yet to be systematically investigated. 

Purpose: To compare the CAR and diurnal cortisol slope between athletes diagnosed with OTS, healthy athletes, and sedentary controls. 

Methods: This study was a secondary analysis of data from the Endocrine and Metabolic Responses on Overtraining study. Male participants were recruited to either OTS, healthy athlete, or sedentary control groups. The participants produced saliva samples immediately after waking (S1), 30 minutes after waking (S2), at 16:00 hours, and at 23:00 hours. Salivary cortisol concentration was determined by an electrochemiluminescence assay. Mixed-effects models were used to assess the conditional effect of group (sedentary controls, OTS, and healthy athletes) on the change in cortisol over time. Separate models were fit for the awakening samples (S1 and S2) and for the diurnal slope (linear change across S1, 16:00 h, and 23:00 h). 

Results: The models demonstrated significant time-by-group interaction for OTS for the 2 cortisol concentrations collected during the awakening period (β = −9.33, P < .001), but not for the diurnal cortisol slope (β = 0.02, P = .80). 

Conclusions: These results suggest the CAR may be associated with OTS and should be considered within a panel of biomarkers. Further research is necessary to determine whether alterations in the CAR may precede the diagnosis of OTS.

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We can Finally Detect when Overtrained Athletes are Recovering


June 27, 2021

Recovery from Overtraining Syndrome

MARKERS OF RECOVERY FROM OVERTRAINING SYNDROME HAVE BEEN UNVEILED FOR THE FIRST TIME 

Overtraining syndrome (OTS) is the most common disease related to sports that leads to a paradoxical reduction in sports performance and symptoms direct- and indirectly related to fatigue, which we proposed to be renamed to Paradoxical Deconditioning Syndrome (PDS), since the paradoxical loss of performance is the main hallmark of the syndrome. Until a short time ago, much remained to be clarified regarding the mechanisms that led to OTS, as well as markers of OTS. In the EROS study, more than 30 specific markers of OTS have been discovered. The recovery of OTS is complex and not always complete: many professional athletes are not able to achieve their previous marks. From the markers unveiled for OTS, we were able to detect which markers predict recovery of OTS from a 3-month program and follow-up of OTS-affected athletes. Basically, athletes that presented a better recovery were able to recover the fast hormonal response to stimulation, improve freeT3 levels, normalize the testosterone:estradiol ratio, and improve the Cortisol Awakening Response (CAR). Conversely, the prolonged hormonal response typically observed in healthy athletes was not recovered, as well as markers of body composition and metabolism.

In conclusion, our study showed that the recovery process from OTS is complex, not easy, prolonged, and not full, which corresponds to the long-term consequences that athletes affected by actual OTS experiment. 

Links:

https://journals.humankinetics.com/view/journals/ijspp/aop/article-10.1123-ijspp.2020-0248/article-10.1123-ijspp.2020-0248.xml

https://pubmed.ncbi.nlm.nih.gov/33406484/ 

Reference:

 

Cadegiani FA, Silva PHL, Abrao TCP, Kater CE. Novel Markers of Recovery From Overtraining Syndrome: The EROS-LONGITUDINAL Study. Int J Sports Physiol Perform. 2021 Jan 5:1-10. doi: 10.1123/ijspp.2020-0248. Epub ahead of print. PMID: 33406484

ABSTRACT 

Purposes: Overtraining syndrome (OTS) is an unexplained underperformance syndrome triggered by excessive training, insufficient caloric intake, inadequate sleep, and excessive cognitive and social demands. Investigation of the recovery process from OTS has not been reported to date. The objective was to unveil novel markers and biochemical and clinical behaviors during the restoration process of OTS. 

Methods: This was a 12-week interventional protocol in 12 athletes affected by OTS, including increase of caloric intake, transitory interruption of training, improvement of sleep quality, and management of stress, followed by the assessment of 50 parameters including basal and hormonal responses to an insulin tolerance test and nonhormonal biochemical markers, and body metabolism and composition. 

Results: Early cortisol (P = .023), late ACTH (adrenocorticotrophic hormone) (P = .024), and early and late growth hormone (P = .005 and P = .038, respectively) responses, basal testosterone (P = .038), testosterone:estradiol ratio (P = .0005), insulinlike growth factor 1 (P = .004), cortisol awakening response (P = .001), and free thyronine (P = .069) increased, while basal estradiol (P = .033), nocturnal urinary catecholamines (P = .038), and creatine kinase (P = .071) reduced. Conversely, markers of body metabolism and composition had slight nonsignificant improvements. 

Conclusion: After a 12-week intervention, athletes affected by actual OTS disclosed a mix of non-, partial, and full recovery processes, demonstrating that remission of OTS is as complex as its occurrence.

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The Clinical Diagnosis of Overtraining Syndrome


June 27, 2021

Diagnosis of Overtraining Syndrome

THE FIRST CLINICAL AND BIOCHEMICAL SCORE FOR PRECISE DIAGNOSIS OF OVERTRAINING SYNDROME HAS BEEN VALIDATED AND PUBLISHED 

Because the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study evaluated more than 100 markers in three groups of subjects, of overtrained athletes, healthy athletes, and healthy non-physically active subjects, aiming do distinguish physiological from pathological hormonal and metabolic changes that occur in athletes, it allowed us structure specific scores for diagnosis of overtraining syndrome. The diagnosis of OTS through the proposed scores did not require the presence of late-stage symptoms like loss of performance and unrefreshing rest, which is highly desirable, once the later the diagnosis, the harder the recovery process.

From an internal validation process, we were able to propose scores at different levels of assessments (whether only clinical markers, basal biochemical markers, or stimulated markers) with 100% accuracy to distinguish OTS-affected from healthy athletes.

This paper makes the diagnosis of OTS less subjective, less time-consuming, and less questionable. It is likely a hallmark in the management of athletes suspected for OTS. 

Links:

https://www.hindawi.com/journals/jsm/2020/3937819/

https://pubmed.ncbi.nlm.nih.gov/32373644/ 

Reference:

Cadegiani FA, da Silva PHL, Abrao TCP, Kater CE. Diagnosis of Overtraining Syndrome: Results of the Endocrine and Metabolic Responses on Overtraining Syndrome Study: EROS-DIAGNOSIS. J Sports Med (Hindawi Publ Corp). 2020;2020:3937819. Published 2020 Apr 22. doi:10.1155/2020/3937819.

Study Abstract

ObjectivesOvertraining syndrome (OTS), a common dysfunction among elite athletes, causes decreased performance and fatigue and has no standardized diagnostic criteria. The Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study identified more than 45 potential biomarkers of OTS. In the present study, we hypothesized that combinations of these biomarkers could be an accurate diagnostic tool for OTS.

MethodsWe selected parameters with largest difference and fewest overlapping results compared to healthy athletes and highest feasibility and reproducibility. Among the multiple combinations attempted, we chose those that did not show overlapping results, according to the objective.

ResultsWe included 11 clinical parameters, 4 basal hormones, and 5 hormonal responses in Insulin Tolerance Test (ITT). The three selected diagnostic tools were the (i) EROS-CLINICAL, with only clinical parameters, which was suitable as an initial assessment for athletes suspected of OTS; (ii) EROS-SIMPLIFIED, with clinical parameters and basal hormones, when the EROS-CLINICAL was inconclusive; and (iii) EROS-COMPLETE, with basal and hormonal responses to stimulation tests, which was valuable for population-based screening, research purposes, and unusual presentations of OTS.

ConclusionWe identified innovative tools with 100% accuracy for the diagnosis of OTS, without the need to exclude confounding disorders.

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Insufficient Eating and Bad Sleep are The Novel Triggers of Overtraining Syndrome


June 27, 2021

Eating and sleeping patterns as triggers of Overtraining Syndrome

INSUFFICIENT CALORIC INTAKE AND SLEEP QUALITY AS NOVEL TRIGGERS OF OTS AND NOVEL CONSEQUENCES OF OTS 

This is a post-hoc analysis of all the arms of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study that evaluated whether and which are the novel triggers of overtraining syndrome (OTS) besides excessive training, the only recognized trigger of OTS to date, and potential novel consequences of OTS.

We detected that insufficient protein intake alone, insufficient carbohydrate intake alone, or insufficient overall caloric intake may trigger OTS even when training is not excessive, and is enhanced by bad sleep quality.

We also discovered that OTS by itself may cause multiple consequences. OTS causes the interruption of the prolonged hormonal response that typically occurs in athletes and that help increase the time-to-fatigue, leading to reduction of the time until fatigue and consequently decreased performance in long-duration sports. OTS reduces the testosterone:estradiol (T:E) probably by enhancing the aromatase enzyme activity pathologically, similarly to what happens in obesity, type 2 diabetes, and other metabolic and inflammatory chronic diseases, increases body fat, decreases muscle mass, reduces metabolic rate, fat oxidation, and level of hydration, decreases levels of vigor, and increases tension and fatigue levels.

The worsening of body composition and metabolism, the decreased motivation, the decreased T:E ratio and the impaired hormonal responses to stimulation altogether may justify the paradoxical decrease of sports performance, the hallmark of OTS. 

Links:

https://pubmed.ncbi.nlm.nih.gov/31548891/

 https://bmcsportsscimedrehabil.biomedcentral.com/articles/10.1186/s13102-019-0132-x

Reference:

Cadegiani FA, Kater CE. Novel causes and consequences of overtraining syndrome: the EROS-DISRUPTORS study. BMC Sports Sci Med Rehabil. 2019 Sep 18;11:21. doi: 10.1186/s13102-019-0132-x. 

Study Abstract

Abstract

Background: Hormonal physiology in athletes, dysfunctional paths leading to overtraining syndrome (OTS), and clinical and biochemical behaviors that are independently modified by the presence of OTS remain unclear. Although multiple markers of OTS have recently been identified, the independent influence of OTS on hormones and metabolism have not been assessed. Hence, the objective of the present study was to uncover the previously unrecognized independent predictors of OTS and understand how OTS independently modifies the behaviors of clinical and biochemical parameters.

Methods: In a total of 39 athletes (OTS-affected athletes (OTS) = 14 and healthy athletes (ATL) = 25), we performed two clusters of statistical analyses using the full data of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study, in a total of 117 markers. We first used logistic regression to analyze five modifiable parameters (carbohydrate, protein, and overall caloric intake, sleep quality, and concurrent cognitive effort) as potential additional independent risk factors for OTS, and OTS as the outcome. We then used multivariate linear regression to analyze OTS as the independent variable and 38 dependent variables. Training patterns were found to be similar between OTS and ATL, and therefore excessive training was not a risk, and consequently not a predictor, for OTS.

Results: Each of the three dietary patterns (daily carbohydrate, daily protein, and daily overall calorie intake) were found to be the independent triggers of OTS, while sleeping, social, and training characteristics depended on other factors to induce OTS. Once triggered, OTS independently induced multiple changes, including reductions of cortisol, late growth hormone and adrenocorticotropic hormone responses to stimulations, testosterone-to-estradiol ratio, neutrophils, neutrophil-to-lymphocyte ratio, vigor levels, hydration status, and muscle mass, while increase of tension levels and visceral fat.

Conclusions: OTS can be independently triggered by eating patterns, regardless of training patterns, while the occurrence of OTS reduced late hormonal responses and the testosterone-to-estradiol ratio, worsened mood, and affected the immunology panel. These novel findings may explain underperformance, which is the key characteristic of OTS.

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Overtraining Syndrome Beyond Overtraining


June 27, 2021

Novel markers and mechanisms on Overtraining Syndrome

THE EROS STUDY DISCOVER NOVEL MARKERS AND MECHANISMS OF OVERTRAINING SYNDROME 

The present study is an overall analysis of all the markers and subjects evaluated by the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study. We had the surprising discovery that the majority of the markers evaluated in athletes affected by overtraining syndrome were neither abnormal nor normal, because when these markers were analyzed through the perspective of the usual reference ranges and healthy sedentary, levels found in OTS-affected athletes were similar. However, when compared to healthy athletes, these markers were different between them. It occurred because several markers were unexpectedly different between healthy athletes and healthy sedentary, which was demonstrated to be physiological endocrine and metabolic adaptations that occur in athletes that had not been described until our study. Considering this, abnormalities in OTS are not overt, but relative instead, since these markers are altered to what would be expected for athletes, but normal if we consider the typical reference ranges.

We also found OTS can occur independently from excessive training, since insufficient calorie, protein, or carbohydrate intake, poor sleep quality, or concurrent excessive cognitive effort were the found to be triggers of OTS, without the need of excessive training for its trigger.

Overall, multiple biochemical and hormonal conditioning processes occur in athletes, which are lost in OTS. OTS results from a mix of losses of conditioning processes, which we termed as 'mix of deconditioning processes'.

The understanding of OTS as a combination of ‘deconditioning processes’ helped to elucidate the underlying reason of the unexplained decrease in performance, the hallmark of OTS.

Since the loss of sports performance was paradoxical to the expected, since we would expect that performance would improve progressively, we found sufficient data to suggest that OTS would be more precisely named as “Paradoxical Deconditioning Syndrome (PDS)”, since PDS seems to be a more appropriate and descriptive name for OTS than the previous misnomer (‘overtraining’).

The EROS study also unveiled the existence of multiple independent metabolic and hormonal adaptations to exercise, in addition to those in cardiovascular, autonomic, and neuromuscular systems. This serendipitous finding may explain some of the health benefits and progressive improvement observed in athletes.

The present analysis is a synthesis of the novel perspective on OTS that the EROS study brought, and helped changed and improved the understanding of the mechanisms of the pathophysiology of OTS, its biomarkers, triggers, and consequences. 

Links:

https://bmjopensem.bmj.com/content/5/1/e000542

https://pubmed.ncbi.nlm.nih.gov/31297238/

Reference:

Cadegiani FA, Kater CE. Novel insights of overtraining syndrome discovered from the EROS study. BMJ Open Sport Exerc Med. 2019 Jun 20;5(1):e000542. doi: 10.1136/bmjsem-2019-000542.  

Study abstract

Abstract

Background: Excessive training and inadequate recovery could cause 'overtraining syndrome' (OTS), which is characterised by underperformance and fatigue. The pathophysiology of OTS is unclear. We aimed to describe novel mechanisms and risk factors associated with OTS, and thereby facilitate its early identification and prevention, from a comprehensive joint qualitative analysis of the findings from all the four arms of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study.

Methods: We compared the types and proportions of behavioural patterns of 67 evaluated parameters of OTS from 51 participants-athletes with OTS (OTS, n=14), healthy athletes (n=25) and healthy non-physically active controls (n=12). We performed overall and pairwise comparisons for statistically significant differences between the three groups (p<0.05).

Results: A total of 44 (65.7%) markers exhibited significant differences between the three groups: 32 (72.7%) showed a loss of the conditioning effect of exercise ('deconditioning'), 7 (15.9%) showed changes exclusive to OTS, 3 (6.8%) maintained the exercise-induced conditioning effects and 2 (4.5%) revealed an exacerbation of the adaptive changes to exercises.

Conclusion: Our findings suggest that OTS is likely triggered by multiple factors, not restricted to excessive training, resulted from a chronic energy deprivation, leading to multiple losses in the conditioning processes typically observed in healthy athletes, as a combination of 'paradoxical deconditioning' processes, which explains the gradual and marked loss of physical conditioning found in OTS. We, therefore, suggest that the term 'paradoxical deconditioning syndrome' better represents the features of this syndrome.

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Crossfit And Related Sports: A Unique Conditioning Level


June 27, 2021

Specific metabolic and endocrine patterns in High-Intensity Functional Training (HIFT)

CROSSFIT AND OTHER HIGH-INTENSITY FUNCTIONAL TRAINING (HIFT) MODALITIES LEAD TO MORE PROMINENT HORMONAL AND METABOLIC ADAPTATIONS THAN OTHER SPORTS, AND WHEN OVERTRAINING SYNDROME OCCURS IN THESE SPORTS, IT TENDS TO BE MILDER WITH POORER MARKERS, AND THEREFORE HARDER TO DIAGNOSE 

CrossFit and other high-intensity functional training (HIFT) sports is a modality with unique characteristic of mixing different abilities and dimensions of the physical conditioning, requiring explosive, strength, stop-and-go, explosive, anaerobic, and aerobic abilities altogether within a single sport.

In the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study, a subpopulation of athletes practiced HIFT, and were compared to all athletes and to non-HIFT athletes.

Athletes that practiced HIFT presented enhanced hormonal and metabolic conditioning processes compared to non-HIFT athletes.

HIFT athletes that developed overtraining syndrome (OTS) presented fewer and milder symptoms that OTS-affected athletes from other modalities, as well as fewer biochemical and body composition and metabolism abnormalities. In addition, low carbohydrate and low overall caloric intake were the main triggers of OTS in HIFT-athletes.

The peculiarities of HIFT sports in terms of the combination of different abilities joined in a single sport reflect in the differences in the level of hormonal and metabolic conditioning processes, as well as in the characteristics of OTS in this sports modality. 

Links:

https://www.tandfonline.com/doi/full/10.1080/02640414.2018.1555912

https://pubmed.ncbi.nlm.nih.gov/30786846/ 

Reference:

Cadegiani FA, Kater CE, Gazola M. Clinical and biochemical characteristics of high-intensity functional training (HIFT) and overtraining syndrome: findings from the EROS study (The EROS-HIFT). J Sports Sci. 2019 Feb 20:1-12. doi: 10.1080/02640414.2018.1555912. 

Study abstract:

Abstract

The metabolic and hormonal consequences of high-intensity functional training regimens such as CrossFit® (CF) are unclear. Little is known about the triggers and clinical and biochemical features of CF-related overtraining syndrome (OTS). The EROS study compared endocrine and metabolic responses, and eating, social, psychological and body characteristics of OTS-affected (OTS) and healthy athletes (ATL), and non-physically active controls (NPAC). The current study is a post-hoc analysis of the CF subgroups of the EROS study, to evaluate specific characteristics of CF in ATL and OTS. Parameters were overall and pairwise compared among OTS-affected (CF-OTS) and healthy (CF-ATL) athletes that exclusively practiced CF, and NPAC. CF-ATL yielded earlier and enhanced cortisol, GH, and prolactin responses to an insulin tolerance test (ITT), increased neutrophils, lower lactate, increased testosterone, improved sleep quality, better psychological performance, increased measured-to-predicted basal metabolic rate (BMR) ratio and fat oxidation, and better hydration, when compared to NPAC. Conversely, more than 90% of the adaptive changes in CF were lost under OTS, including an attenuation of the hormonal responses to an ITT, increased estradiol, decreased testosterone, and decreased BMR and fat oxidation; the most remarkable trigger of OTS among "HIFT athletes" was the long-term low carbohydrate and calorie intake.

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Insufficiencies, not Excesses, Lead to Overtraining Syndrome


June 27, 2021

Triggers and consequences of Overtraining Syndrome

INSUFFICIENT FOOD, INSUFFICIENT SLEEP, AND INSUFFICIENT REST WERE FOUND TO BE TRIGGERS OF OVERTRAINING SYNDROME, AND OVERTRAINING SYNDROME CAUSES INCREASE OF BODY FAT, AND DECREASE OF MUSCLE MASS, FAT BURNING, HYDRATION, AND MOOD STATES.

The present study is the arm of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study that evaluated body composition, metabolism, sleep, psychological and eating patterns of overtraining and healthy athletes, and healthy sedentary subjects.

We found out that athletes affected by OTS had significantly worse sleep quality, worked or studied for longer periods of time, ate fewer calories, less protein, and less carbohydrate, had decreased libido, worse mood states, decreased basal metabolic rate, decrease fat burning, increased body fat, decreased muscle mass, and were less hydrated than healthy athletes. When compared to sedentary, OTS-affected athletes had similar levels of almost all markers, except for lower libido, lower vigour, and increased fatigue, compared to sedentary. 

Overtraining syndrome demonstrated to be a combination of multiple abnormalities in body composition and metabolism, and psychological states, and presented differences in terms of habits, since OTS-affected athletes had worse sleep quality, had more cognitive demands, and ate less calories, protein, and carbohydrate, than healthy athletes. 

Links:

https://www.tandfonline.com/doi/full/10.1080/02640414.2018.1424498

https://pubmed.ncbi.nlm.nih.gov/29313445/ 

Reference:

Cadegiani FA, Kater CE. Body composition, metabolism, sleep, psychological and eating patterns of overtraining syndrome: results of the EROS study (EROS-PROFILE). J Sports Sci. 2018 Aug;36(16):1902-1910. doi: 10.1080/02640414.2018.1424498. PMID: 29313445.  

Study abstract

Overtraining syndrome (OTS) is caused by an imbalance between training, nutrition and resting, and leads to decreased performance and fatigue; however, the precise underlying triggers of OTS remain unclear. This study investigated the body composition, metabolism, eating, sleeping patterns and mood states among participants with OTS. Selected participants were divided into OTS-affected athletes (OTS, n = 14), healthy athletes (ATL, n = 25), and healthy non-physically active controls (NCS, n = 12). Compared to ATL, OTS showed decreased sleep quality (p = 0.004); increased duration of work or study (p < 0.001); decreased libido (p = 0.024); decreased calorie (p < 0.001), carbohydrate (p < 0.001) and protein (p < 0.001) intakes; decreased mood states (p < 0.001); decreased basal metabolic rate (p = 0.013) and fat burning (p < 0.001); increased body fat (p = 0.006); decreased muscle mass (p = 0.008); and decreased hydration (p < 0.001). Levels were similar between OTS and NCS, except for worsened fatigue (p < 0.001) and vigour (p = 0.001) in OTS. Reduced calorie intake, worsened sleep, and increased cognitive activity are likely OTS triggers. OTS appears to induce dehydration, increase body fat, decrease libido, and worsen mood.

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It’s All About Hormones, Buddy


June 27, 2021

Basal hormones and Overtraining Syndrome 

NOT ONLY WHEN HORMONES ARE EVALUATED UNDER STIMULATIONS THAT OVERTRAINED ATHLETES CAN BE DETECTED. EASIER ANALYSIS OF BASAL RESTING HORMONAL LEVELS MAY ALSO ALLOW TO DETECT MARKERS OF OVERTRAINING SYNDROME (OTS).

The present analysis is the arm of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study that evaluated hormonal, inflammatory, immunologic, and muscular basal markers in athletes affected by OTS, healthy athletes, and healthy sedentary subjects. All groups were sex-, age-, and body mass index (BMI)-matched.

Healthy athletes demonstrated higher testosterone levels, increased neutrophil:lymphocyte ratio, paradoxical decreased lactate levels, and increased nocturnal urinary catecholamines (NUC). These are likely among the multiple hormonal, metabolic, muscular, and immunologic conditioning processes that athletes undergo along with progressive increase of training volume, intensity, and load.

Increased neutrophil:lymphocyte ratio is typically a marker of worse prognosis in acute severe states. However, physiologically, it may be an adaptive process in athletes to provide further immunologic support, since these athletes do not present reduction of lymphocytes.

Decreased lactate was another unexpected finding in healthy athletes since it increases with training, although the blood exams were collected 48 hours after the last training session. Possibly, increased lactate clearance may occur, what is typically called as “faster muscle recovery”.

When affected by OTS, athletes experiment a loss of many of these adaptive processes, an exacerbation of NUC, and disproportionally increased muscular parameters. Increased lactate and CK levels help explain why overtrained athletes tend to complain of “prolonged and impaired muscle recovery”. Exacerbated NUC may reflect an attempt to keep body functioning under the dysfunctional state of OTS.

A remarkable finding was the pathological reduction of the testosterone:estradiol (T:E) ratio, reduced by 50% when compared to both healthy athletes and healthy sedentary. It means that reduced T:E ratio is an overt abnormality, specific of OTS when detected in athletes. Reduction of the T:E ratio may also be found in obesity, diabetes, and other metabolic and inflammatory diseases. It occurs likely as a result of a pathological exacerbation of aromatase activity, which is the enzyme that converts testosterone into estradiol. Unlike when estradiol raises in consequence of increase of testosterone, that leads to benefits including increase of muscle and bone mass, libido, and energy levels, but when the T:E proportion is maintained, in the case of increase of estradiol due to enhanced aromatase activity leads to reduction of testosterone and consequently reduction of the T:E ratio.

As seen above, multiple basal markers also allow help to diagnose of athletes suspected of OTS. And we also learned that exercise may lead to more benefits than previously thought. 

Links:

https://meridian.allenpress.com/jat/article/54/8/906/420847/Basal-Hormones-and-Biochemical-Markers-as

https://pubmed.ncbi.nlm.nih.gov/31386577/ 

Reference:

Cadegiani FA, Kater CE. Basal Hormones and Biochemical Markers as Predictors of Overtraining Syndrome in Male Athletes: The EROS-BASAL Study. J Athl Train. 2019 Aug;54(8):906-914. doi: 10.4085/1062-6050-148-18.  

Study abstract

Abstract

ContextOvertraining syndrome (OTS) and related conditions cause decreased training performance and fatigue through an imbalance among training volume, nutrition, and recovery time. No definitive biochemical markers of OTS currently exist.

ObjectiveTo compare muscular, hormonal, and inflammatory parameters among OTS-affected athletes, healthy athletes, and sedentary controls.

DesignCross-sectional study.

SettingLaboratory.

Patients or other participants: Fifty-one men aged 18 to 50 years (14 OTS-affected athletes [OTS group], 25 healthy athletes [ATL group], and 12 healthy sedentary participants [NCS group]), with a body mass index of 20 to 30.0 kg/m2(sedentary) or 20 to 33.0 kg/m2(athletes), recruited through social media. All 39 athletes performed both endurance and resistance sports.

Main outcome measure(s): We measured total testosterone, estradiol, insulin-like growth factor 1, thyroid-stimulating hormone, free thyronine, total and fractioned catecholamines and metanephrines, lactate, ferritin, creatinine, creatine kinase, erythrocyte sedimentation rate, C-reactive protein, lipid profile, hemogram, and testosterone : estradiol, testosterone : cortisol, neutrophil : lymphocyte, platelet: lymphocyte, and catecholamine : metanephrine ratios. Each parameter was statistically analyzed through 3-group comparisons, and wheneverP< .05, pairwise comparisons were performed (OTS × ATL, OTS × NCS, and ATL × NCS).

Results: Neutrophils and testosterone were lower in the OTS group than in the ATL group but similar between the OTS and NCS groups. Creatine kinase, lactate, estradiol, total catecholamines, and dopamine were higher in the OTS group than in the ATL and NCS groups, whereas the testosterone : estradiol ratio was lower, even after adjusting for all variables. Lymphocytes were lower in the ATL group than in the OTS and NCS groups. The ATL and OTS groups trained with the same intensity, frequency, and types of exercise.

Conclusions: At least in males, OTS was typified by increased estradiol, decreased testosterone, overreaction of muscle tissue to physical exertion, and immune system changes, with deconditioning effects of the adaptive changes observed in healthy athletes.

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A Sort of Relative Adrenal Insufficiency Happens in Overtraining Syndrome


June 27, 2021

Cortisol and Overtraining Syndrome

OVERTRAINING SYNDROME LEADS TO REDUCTION OF CORTISOL RELEASE IN RESPONSE TO STIMULATIONS AND IMPAIRED CORTISOL RESPONSE TO AWAKENING 

The EROS-HPA axis arm of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study evaluated the hypothalamus-pituitary-adrenal (HPA) axis at all level, by directly stimulating the adrenal gland and by stimulation the whole HPA axis through an insulin tolerance test (ITT), that causes a stressful environment by causing hypoglycemia.

All groups, of athletes affected by overtraining syndrome, healthy athletes, and healthy sedentary, had similar direct adrenal responses to a stimulation with synthetic ACTH, showing that neither healthy athletes disclose direct adrenal enhancement, nor OTS-affected athletes had impaired adrenal responses.

Conversely, when the whole HPA axis is stimulated through an ITT, the pituitary hormone that stimulates cortisol, called adrenocorticotropic hormone (ACTH), and the cortisol are released in sequence, aiming to counterbalance the hypoglycemic state, since cortisol is an insulin counter-regulator, i.e., a hormone that induces hyperglycemia. The ITT is a type of stimulation test that stimulates the hypothalamus directly, without interference from other systems, and can tell about the hypothalamic-pituitary axes precisely.

Healthy athletes demonstrated prompter, enhanced, and prolonged ACTH and cortisol response than healthy sedentary. Considering that this stimulation is independent of exercise, any physical effort, and also independent of cardiovascular, musculoskeletal or any other system, these differences provide sufficient substantiation to conclude that HPA axis responses to stimulations are optimized in athletes, regardless of physical activity. 

Links:

https://sportsmedicine-open.springeropen.com/articles/10.1186/s40798-017-0113-0

https://pubmed.ncbi.nlm.nih.gov/29222606/ 

Reference:

Cadegiani FA, Kater CE. Hypothalamic-pituitary-adrenal (HPA) axis functioning in overtraining syndrome: findings from Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) - EROS-HPA axis. Sports Med Open. 2017 Dec 8;3(1):45. DOI: 10.1186/s40798-017-0113-0. PMID: 29222606. 

Study abstract

Background

Overtraining syndrome (OTS) results from excessive training load without adequate recovery and leads to decreased performance and fatigue. The pathophysiology of OTS in athletes is not fully understood, which makes accurate diagnosis difficult. Previous studies indicate that alterations in the hypothalamus-pituitary-adrenal (HPA) axis may be responsible for OTS; however, the data is not conclusive. This study aimed to compare, through gold standard and exercise-independent tests, the response of the HPA axis in OTS-affected athletes (OTS group) to healthy physically active subjects (ATL group) and healthy non-active subjects (NCS group).

Methods

Selected subjects were evaluated for cortisol response to a 250-μg cosyntropin stimulation test (CST), cortisol and adrenocorticotropic hormone (ACTH) responses during an insulin tolerance test (ITT), and salivary cortisol rhythm (SCR).

Results

A total of 51 subjects were included (OTS, n = 14; ATL, n = 25; and NCS, n = 12). Cortisol response in the CST was similar among the three groups. Conversely, mean cortisol response during an ITT was significantly higher in ATL (21.7 μg/dL; increase = 9.2 μg/dL) compared to OTS (17.9 μg/dL; 6.3 μg/dL) and NCS (16.9 μg/dL; 6.0 μg/dL) (p ≤ 0.001; p = 0.01). Likewise, median ACTH response during an ITT was significantly higher in ATL (91.4 pg/mL; increase = 45.1 pg/mL) compared to OTS (30.3 pg/mL; 9.7 pg/mL) and NCS (51.4 pg/mL; 38.0 pg/mL) (p = 0.006; p = 0.004). For SCR, mean cortisol 30 min after awakening was significantly higher in ATL (500 ng/dL) compared to OTS (323 ng/dL) and NCS (393 ng/dL) (p = 0.004). We identified the following cutoffs that could help exclude or confirm OTS: cortisol level at 30 min after awakening (exclusion = > 530 ng/dL); cortisol response to ITT (exclusion = > 20.5 μg/dL; confirmation = < 17 μg/dL or increase < 9.5 μg/dL); and ACTH response (exclusion = > 106 pg/mL or increase > 70 pg/mL; confirmation = < 35 pg/mL and increase < 14.5 pg/mL).

Conclusion

The findings of the present study showed that healthy athletes disclose adaptions to exercises that helped improve sport-specific performance, whereas this sort of hormonal conditioning was at least partially lost in OTS, which may explain the decrease in performance in OTS.

Key-points

  • The hypothalamus-pituitary-adrenal (HPA) axis response to ITT are exacerbated in healthy athletes, compared to sedentary healthy subjects. ITT may be a tool to evaluate whether the athlete is well-conditioned and to predict performance, once the exacerbation of the HPA axis responses may play an important role in the progressive improvement in sports performance.
  • There are intrinsic dysfunctions of the HPA axis response to a stress situation in OTS-affected athletes, compared to healthy athletes, in an independent way from exercise-induced stimulation; the dysfunctions of the HPA axis are located in the hypothalamus and the pituitary, and not the adrenals. In case an athlete is suspected for OTS, an ITT stimulation test may be performed. In the absence of confounding diseases, blunted cortisol and ACTH responses most likely confirm the diagnosis of OTS, with accurate cutoffs.
  • Two new concepts were unprecedentedly demonstrated by the study. The first new concept is that physical activity, at least moderate-to-intense, elicits conditioning effects of hormonal responses to stimulation that goes beyond exercise, which we called as “hormonal conditioning of the athlete”. Besides helping explain the improvement in the sports performance, the novel conditioning process found by our study may be the missing link for the understanding of the underlying mechanisms of the improvement observed in several responses to harmful situations, such as infections, neoplasms, traumas, inflammations, and psychiatric conditions that are observed in athletes, and which were not fully understood so far. The second concept is that whereas healthy athletes seem to present hormonal conditioning adaptions, those affected by overtraining seem to have impaired or maladapted hormonal conditioning, as over-trained athletes have a blunted optimized hormone response to stress that seem to be acquired by athletes; as a sort of deconditioning process, which indicates that the decreased performance and the reduced time-to-fatigue observed during OTS; these two key features of OTS, not yet fully understood, may be at least partly explained by the present findings.

Despite these unprecedented findings, further studies are recommended to confirm our results.

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What happens to hormones in healthy and in overtrained athletes?


June 27, 2021

Hormonal responses to stress in healthy and overtraining athletes

HORMONES ARE OPTIMIZED IN HEALTHY ATHLETES, WHEREAS BLUNTED IN OVERTRAINING SYNDROME 

The EROS-STRESS arm of the Endocrine and metabolic Responses on Overtraining Syndrome (EROS) study evaluated the hormonal responses to a non-exercise, direct stimulation test to the hypothalamic-pituitary axes, except for cortisol and ACTH, which have been described in the EROS-HPA axis arm. The EROS-STRESS arm also described the symptoms of hypoglycemia experimented during the stimulation test, which was an Insulin Tolerance Test (ITT).

Surprisingly, we detected increased basal GH in healthy athletes compared to healthy sedentary, while it was blunted in athletes affected by overtraining syndrome (OTS). This is surprising because GH is released in peaks for a few minutes but remains undetectable the majority of the time, particularly in males. Even adjusting by the removal of outliers, which in this case were those that collected blood during a GH peak, differences remained significantly. Whether there is any role of the detectable, instead of indetectable, basal GH in athletes is unknown.

Likewise, basal prolactin was also higher in healthy athletes compared to sedentary, but lower in OTS-affected athletes compared to healthy athletes. Both basal hormones were similar between OTS and sedentary.

In response to the stimulation test, GH reached a peak approximately 04 times higher in healthy athletes than both overtrained athletes and healthy sedentary. GH was also released more promptly and the peak remained for longer periods of time in healthy athletes. It means that healthy athletes are conditioned to release GH more quickly, at higher levels, and to keep releasing for longer, even when stimulation does not come from exercise or from cardiovascular or musculoskeletal systems. All these characteristics seem to be lost in OTS.

Healthy athletes were the only group that experimented a significant increase of prolactin in response to an ITT. The groups of OTS-affected athletes and sedentary did not present any significant prolactin release. Since prolactin release is associated with improvement of stress responses, this may be an additional beneficial conditioning process that athletes undergo, and which is also lost in OTS.

Hypoglycemia leads to two types of symptoms: those derived from hyperadrenergic release and symptoms resulted from neuroglycopenia. Interestingly, overtrained athletes had fewer adrenergic symptoms, already adjusted for glucose levels. The loss of adrenergic symptoms usually occurs in patients affected by type 1 or 2 diabetes that present several episodes of hypoglycemia or remain under hypoglycemia for long periods of time. Their body gets kind of ‘used’ to hypoglycemia and lose sensitivity to adrenergic release, leading to fewer and milder symptoms. Possibly, athletes affected by OTS may train or spend more time under unnoticed hypoglycemia, which makes sense when we consider that their hormonal responses to simulation are weaker than expected, and they usually train in an intensity that surpasses the ability of the body to generate glucose from ammino acids and lipids (a process called gluconeogenesis), associated with depleted storage of glycogen, which is also typically found in OTS. 

The study shows that athletes affected by OTS present similar patterns of the sedentary, as a sort of regression of their improvement, which matches with the regression in terms of physical performance. 

Links:

https://www.jsams.org/article/S1440-2440(17)31746-2/fulltext

https://pubmed.ncbi.nlm.nih.gov/29157780/ 

Reference:

Cadegiani FA, Kater CE. Hormonal responses to a non-exercise stress test in athletes with overtraining syndrome: results from the Endocrine and metabolic Responses on Overtraining Syndrome (EROS) - EROS-STRESS. J Sci Med Sport. 2018 Jul;21(7):648-653. DOI: 10.1016/j.jsams.2017.10.033. PMID: 29157780.  

Study abstract

Objectives: Overtraining syndrome (OTS) leads to worsened sports performance and fatigue. The pathophysiology of OTS has not been entirely elucidated, and there is a lack of accurate markers for its diagnosis. Changes in hormonal responses implicated in OTS were stimulated by exercise, which has limited their interpretation. Hence, we aimed to evaluate growth hormone (GH) and prolactin responses to a gold-standard and exercise-independent stimulation test, the insulin tolerance test (ITT).

Design: Volunteers were recruited and divided into OTS-affected athletes (OTS), healthy athletes (ATL), and healthy non-active subjects (NCS) groups, after general and specific inclusion and exclusion criteria.

Methods: We evaluated the responses of growth hormone (GH) and prolactin to the ITT, and compared between groups.

Results: A total of 51 subjects were included (OTS, n=14, ATL, n=25, and NCS, n=12). OTS disclosed significantly lower basal levels of GH (p=0.003) and prolactin (p=0.048), and GH (p=0.001) and prolactin (p<0.001) responses to ITT (p=0.001), compared to ATL, but similar to NCS. OTS showed a later rise in GH levels in response to hypoglycemia, compared to ATL, but not to NCS. We suggest cutoffs for GH and prolactin levels to aid in the diagnosis of OTS.

Conclusions: OTS-affected athletes show reduced GH and prolactin basal levels and responses to a non-exercise stress test compared to healthy athletes, but not to sedentary subjects.

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The Systematic Review That Led to The Eros Study


June 27, 2021

Systematic review of the hormonal aspects of Overtraining Syndrome

STIMULATED, RATHER THAN BASAL HORMONES, WERE BETTER INDICATORS OF OVERTRAINING SYNDROME, ACCORDING TO A SYSTEMATIC REVIEW PRIOR TO THE EROS STUDY

We conducted a systematic review on the hormonal characteristics of athletes affected by overtraining syndrome (OTS). From hundreds of articles, 38 were included after the selection criteria.

Basically, the vast majority measured athletes that were not in actual overtraining, but in a forced state of overreaching instead. Both overreaching and overtraining leads to fatigue and decreased performance, but overreaching is an acute reaction and is rapidly recovered, while overtraining is a long-term, not easily recoverable, that also presents psychological aspects.

Also, athletes were from a wide variety of sports, levels of conditioning, and assessment methods were highly heterogeneous.

Basal hormones were shown to be similar between healthy and OTS-affected athletes, while stimulated GH and ACTH tended to be blunted in OTS. Other hormonal findings were conflicting.

Another message from the systematic review is the urgent need for standardization and uniformization for the evaluation methods for hormones, in order to allow further direct comparisons and metanalysis.

Links:

https://bmcsportsscimedrehabil.biomedcentral.com/articles/10.1186/s13102-017-0079-8

https://pubmed.ncbi.nlm.nih.gov/28785411/ 

Reference:

Cadegiani FA, Kater CE. Hormonal aspects of overtraining syndrome: a systematic review. BMC Sports Sci Med Rehabil. 2017 Aug 2;9:14. DOI: https://doi.org/10.1186/s13102-017-0079-8 PMID: 28785411. 

Study abstract

Background: Overtraining syndrome (OTS), functional (FOR) and non-functional overreaching (NFOR) are conditions diagnosed in athletes with decreased performance and fatigue, triggered by metabolic, immune, hormonal and other dysfunctions and resulted from an imbalance between training stress and proper recovery. Despite previous descriptions, there is a lack of a review that discloses all hormonal findings in OTS/FOR/NFOR. The aim of this systematic review is to evaluate whether and which roles hormones play in OTS/FOR/NFOR.

Methods: A systematic search up to June 15th, 2017 was performed in the PUBMED, MEDLINE and Cochrane databases following PRISMA protocol, with the expressions: (1)overtraining, (2)overreaching, (3)overtrained, (4)overreached, or (5)underperformance, and (plus) (a)hormone, (b)hormonal, (c)endocrine, (d)adrenal, (e)cortisol, (f)GH, (g)ACTH, (h)testosterone, (i)IGF-1, (j)TSH, (k)T4, (l)T3, (m)LH, (n)FSH, (o)prolactin, (p) IGFBP-3 and related articles.

Results: A total of 38 studies were selected. Basal levels of hormones were mostly normal in athletes with OTS/FOR/NFOR compared with healthy athletes. Distinctly, stimulation tests, mainly performed in maximal exercise conditions, showed blunted GH and ACTH responses in OTS/FOR/NFOR athletes, whereas cortisol and plasma catecholamines showed conflicting findings and the other hormones responded normally.

Conclusion: Basal hormone levels are not good predictor but blunted ACTH and GH responses to stimulation tests may be good predictors of OTS/FOR/NFOR.

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Athletes can now know when they are Improving from Overtraining Syndrome


June 27, 2021

This is the study presented at The Endocrine Society meeting in 2020 where we published the parameters of recovery from Overtraining Syndrome (OTS) found in the longitudinal follow-up of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study. This study had its full content further published in another journal in the beginning of 2021.

We showed that markers of recovery include increase of early cortisol and early and late GH response to stimulation, increase in the testosterone:estradiol ratio, freeT3, IGF-1, and cortisol awakening response (CAR).

In common, these are markers that can also be observed during the recovery process of other chronic diseases, including metabolic and inflammatory ones, which reinforces the multifactorial and complex pathophysiology of OTS.

Cadegiani F, da Silva PLH, Abrao TPC, Kater CE. Novel Hormonal and Metabolic Markers of Recovery From Overtraining Syndrome Unveiled by the Longitudinal ARM of the Eros Study - the Eros-Longitudinal Study.J Endocr Soc. 2020;4(Suppl 1):SAT-LB4. Published 2020 May 8. doi:10.1210/jendso/bvaa046.2337.

Links:
https://academic.oup.com/jes/article/4/Supplement_1/SAT-LB4/5834033
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7208838/

Abstract

Background: Overtraining Syndrome (OTS) is an unexplained underperformance syndrome triggered by excessive training, insufficient caloric intake, inadequate sleep, and excessive cognitive and social demands. Investigations of markers of the challenging recovery from OTS have not been reported to date. The objective of the present study is to describe novel markers, and biochemical and clinical behaviors during the restoration process of OTS.Design: A 12-week interventional protocol in 12 athletes affected by OTS was conducted, including increased food intake, transitory interruption of the trainings, improvement of sleep quality, and management of stress.Methods: We assessed 50 parameters, including hormonal responses to an insulin tolerance test (ITT), basal hormonal and non-hormonal biochemical markers, body metabolism and composition. Results: In response to an ITT, early cortisol (p = 0.026), early GH (p = 0.004), and late GH (p = 0.037) improved significantly. Basal estradiol (p = 0.0002) and nocturnal urinary catecholamines, (p = 0.043) reduced, while testosterone (p = 0.014), testosterone:estradiol (T:E) ratio (p = 0.0005), freeT3 (p = 0.043), IGF-1 (p = 0.003), and cortisol awakening response (CAR) (p = 0.001) increased significantly. All basal parameters and early responses to ITT normalized, when compared to healthy athletes. Basal metabolic rate, fat oxidation, body fat, muscle mass, and hydration status had partial but non-significant improvements. Conclusion: After 12 weeks, athletes affected by actual OTS demonstrated substantial improvements, remarkably IGF-1, freeT3, CAR, testosterone, estradiol testosterone:estradiol ratio, CK and catecholamines, and early cortisol, early prolactin, and overall GH responses to stimulations.

overtraining-syndrome-image-31

 

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