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Trends in Psychiatry and Psychotherapy

Print version ISSN 2237-6089On-line version ISSN 2238-0019

Trends Psychiatry Psychother. vol.40 no.4 Porto Alegre Oct./Dec. 2018 

Review Article

Can physical exercise modulate cortisol level in subjects with depression? A systematic review and meta-analysis

O exercício físico pode modular os níveis de cortisol em indivíduos com depressão? Uma revisão sistemática e metanálise

Ana Heloisa Nascimento Beserra1  2 

Priscila Kameda1  2 

Andrea Camaz Deslandes1  2 

Felipe Barreto Schuch3 

Jerson Laks1  4 

Helena Sales de Moraes1  2 

1Instituto de Psiquiatria, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil

2Laboratório de Neurociência do Exercício (LaNEx), UFRJ, Rio de Janeiro, RJ, Brazil

3Centro Universitário La Salle, Canoas, RS, Brazil

4Programa de Pós-Graduação em Biomedicina Translacional, Universidade do Grande Rio (Unigranrio), Duque de Caxias, RJ, Brazil



Major depressive disorder (MDD) is a prevalent medical illness that is associated with chronic stress. Patients with MDD can show an imbalance in cortisol levels, which can be restored with the remission of symptoms. Physical exercise training has been used as a tool to promote changes in cortisol levels in healthy individuals. However, it is unknown if exercise can produce the same results in individuals with MDD.


To review evidence of cortisol changes after exercise training in individuals with MDD.


We conducted a search on PubMed, SciELO, LILACS, ISI Web of Knowledge, Scopus, and PsycInfo databases. Random effects meta-analysis was performed and standardized mean difference (SMD) effect size was calculated. Analyses of forest and funnel plots was conducted using Stata v.11.0 software.


At first, 463 studies were obtained in the search. After completion of the selection procedure, five articles with seven analyses were included. Type of exercise, frequency of training, cortisol measurement, and type of control group were analyzed. There was a reduction of cortisol levels in the exercise group (SMD = −0.65, 95%CI 1.30-0.01). Moreover, sensitivity analysis and subgroup analyses revealed an effect of type (aerobic exercise) and frequency (five times per week) of exercise on reduction of cortisol levels. However, these results should be interpreted cautiously due to the small number of studies and a substantial heterogeneity among them.


Physical exercise promotes a reduction in cortisol levels in individuals with MDD. However, this finding can be influenced by type of exercise, weekly frequency, and type of cortisol measurement.

Keywords: Physical activity; depression; cortisol; HPA axis; exercise



A depressão maior (DM) é uma doença associada ao estresse crônico que pode apresentar um desequilíbrio nos níveis de cortisol, podendo ser recuperado com a remissão dos sintomas. O exercício tem sido utilizado como uma ferramenta para promover mudanças nos níveis de cortisol em indivíduos saudáveis. No entanto, não se sabe se o exercício produz os mesmos resultados em indivíduos com DM.


Revisar evidências de alterações dos níveis de cortisol após o exercício em indivíduos com DM.


Foi realizada busca nas bases de dados PubMed, SciELO, LILACS, ISI Web of Knowledge, Scopus e PsycInfo. Procedeu-se a metanálise com o cálculo do tamanho do efeito da diferença de média padronizada. Foi utilizado o software Stata v.11.0.


Foram obtidos na busca 463 estudos. Após o procedimento de seleção, cinco artigos com sete análises foram incluídos. O tipo de exercício, frequência de treinamento, tipo de medida do cortisol e tipo de grupo controle foram analisados como subgrupos. Houve uma redução dos níveis de cortisol no grupo de exercício. Além disso, a análise de sensibilidade e análises de subgrupos revelaram um efeito do tipo (exercício aeróbico) e da frequência (cinco vezes por semana) de exercício na redução dos níveis de cortisol. No entanto, esses resultados devem ser interpretados com cautela, devido ao pequeno número de estudos e uma heterogeneidade substancial entre eles.


O exercício promove redução dos níveis de cortisol em indivíduos com DM. No entanto, esse achado pode ser influenciado pelo tipo de exercício, medida do cortisol e frequência semanal.

Descritores: Atividade física; depressão; cortisol; eixo HPA; exercício


Major depressive disorder (MDD) is a prevalent medical illness that comprises a variety of different symptoms (e.g., depressed mood, anhedonia, changes in appetite and sleeping, loss of energy, somatic symptoms and others).1 The pathophysiology of MDD is related to several neurobiological changes, including hypothalamic-pituitary-adrenal (HPA) axis malfunction and consequent increase24 or decrease57 in basal cortisol levels. Previous studies have shown that pharmacological treatment can modulate cortisol levels independently of promoting remission of depressive symptoms.810 Although drug therapy is the most common treatment for MDD, alternative treatments have been used in research as well as in clinical practice, mainly due to response failure to drug treatment.1113

Previous studies have investigated the effect of physical exercise training on MDD and significant reduction of depressive symptoms has been found.1416 A meta-analysis reinforced that physical exercise is an effective non-pharmacological treatment for depression in older adults.17 There are several physiological hypotheses to explain the positive effect of exercise on MDD, including HPA changes.18,19 Physical exercise can modulate cortisol levels after a single session of exercise or after physical exercise training,20 possibly due to an upregulation of glucocorticoid receptor.21 However, it is still unknown whether exercise training might promote the same cortisol effects in individuals with MDD.

A previous article suggested that mindful exercise involving body movement and breathing can reduce stressful signals to the limbic system and thus HPA activity, resulting in reduced release of adrenal glucocorticoid.22 Likewise, this hypothesis might be extrapolated to other types of exercise. A previous study from our laboratory showed that the differences in basal cortisol between MDD and healthy control groups can be modulated by physical performance aspects.23 However, although the association between HPA malfunction and MDD has been investigated for five decades,24 few interventional studies have evaluated the effect of physical exercise on cortisol levels in individuals with MDD, and the few results available are contradictory. Some studies have observed significant effect after aerobic training25,26 or holistic training,27,28 while others have shown non-significant changes after strength or aerobic training29,30 or holistic activities.3133

Therefore, the aim of the present study was to systematically review the literature investigating the effects of physical exercise training on cortisol levels in subjects with MDD and to explore potential moderators of this relationship. It is expected that physical exercise has an important effect on cortisol levels in individuals with MDD.


Protocol and registration

This study was registered on the International Prospective Register of Systematic Reviews (PROSPERO) under protocol no. CRD42018055996.

Eligibility criteria

The present systematic review and meta-analysis was conducted according to the PICO search strategy34 and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement.35 Our search permitted the selection of studies conducted in any country and reported in any language. Studies published anytime up to the day of the search (March 02 2018) were considered.

The inclusion criteria were randomized and controlled studies that investigated the effects of exercise training on cortisol levels in individuals with MDD compared to a control group. Also, MDD was defined through the use of established cut-offs for depression screening instruments (e.g., Geriatric Depression Scale [GDS], Center for Epidemiological Scale Depression [CES-D]) or diagnosed using structured or semi-structured diagnostic interviews (e.g., instruments based on criteria from the Diagnostic and Statistical Manual of Mental Disorders [DSM] or the International Classification of Diseases [ICD]). Control groups consisted of sedentary, no exercise, usual routine care, or relaxation.

Information sources

Two investigators (AHNB, PK) conducted a computer search on the PubMed, SciELO (Scientific Electronic Library), LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde), ISI Web of Knowledge (Institute for Scientific Information), Scopus, and PsycInfo databases. Studies published anytime up to March 02 2018 were included.


The search strategy was performed using a combination of the keywords "exercise" AND "cortisol" AND "depression" with the descriptors "physical activity" AND "major depression". The details of the search were as follows: ("exercise" [All Fields] AND "cortisol" [All Fields] AND "depression" [All Fields]). Mesh terms: ("depressive disorder" [MeSH Terms] OR ("depressive" [All Fields] AND "disorder" [All Fields]) OR "depressive disorder" [All Fields] OR "depression" [All Fields] OR "depression" [MeSH Terms]) AND ("exercise" [MeSH Terms] OR "exercise" [All Fields]) AND ("hydrocortisone" [MeSH Terms] OR "hydrocortisone" [All Fields] OR "cortisol" [All Fields]). In some databases, filters were added for "Human" and "Clinical Trial" (PubMed) and "Document type" (Scopus and PsycInfo).

Study selection

Two investigators (AHNB, PK) selected the articles potentially eligible based on the analysis of the title (first selection) and abstract (second selection). Studies meeting any of these criteria were excluded: duplicate studies; studies with animal models; no original data (e.g., reviews); no control group; including patients with other clinical comorbidities (such as cancer, rheumatoid arthritis, alcohol dependence, other psychiatric disorders); evaluating dexamethasone response or acute effects (a single bout of exercise); or no data reported (mean and standard deviation). The full texts of the studies selected were evaluated independently and the meta-analysis was performed.

Data collection process

Two authors (AHNB, HSM) extracted the data from each study and entered them into a table with the following information: sample (age group, sex, clinical diagnosis), exercise method (type, intensity and duration of physical activity), cortisol method (type and time of collection), cortisol levels, and depressive symptoms.

Risk of bias in individual studies

Risk of bias was assessed according to the Physiotherapy Evidence Database (PEDro) scale,36 considering the following items: eligibility criteria; subjects were randomly allocated to groups; allocation was concealed; the groups were similar at baseline regarding the most important prognostic indicators; there was blinding of all subjects; there was blinding of all therapists who administered the therapy; there was blinding of all assessors who measured at least one key outcome; measures of at least one key outcome were obtained from more than 85% of the subjects initially allocated to groups; all subjects for whom outcome measures were available received the treatment or control condition as allocated or, where this was not the case, data for at least one key outcome was analyzed by intention to treat; the results of between-group statistical comparisons are reported for at least one key outcome; and the study provides both point measures and measures of variability for at least one key outcome The score of this scale can range from 0 to 10 (yes = 1; no = 0). The first item was not included in the total score. Studies were considered to be of good quality when a score of 6 to 8 was reached, of moderate quality when the score was 4 to 5, and of poor quality when the score was below 3.

Statistical analysis

We performed a random effects meta-analysis and estimated the effect size using standardized mean differences (SMD). The SMD was calculated considering as continuous variables the mean and standard deviation of cortisol level post-intervention in each group (intervention and control) for each study. Analyses were performed using the Stata v.11.0 software, incorporating fixed- and random-effects assumptions. Fixed- and random-effects analyses did not yield different results; therefore, only the results of the random-effects analyses are here reported, as in this type we considered mostly the heterogeneity of the studies.

Heterogeneity was analyzed according to Higgins & Green,37 i.e., I2 statistics under 40% suggest that the heterogeneity among studies may not be important, whereas values over 75% indicate considerable heterogeneity. Estimates with p-values < 0.05 were considered statistically significant. We used the scale suggested by Hopkins et al.38 to interpret the data, according to the following classification: < 0.20, trivial; 0.20-0.60, small; 0.61-1.20, moderate; 1.21-2.00, large; 2.01-4.00, very large; > 4.00, almost perfect. Forest plots were used to present our main findings, and funnel plots, potential publication bias and afterward sensitivity analysis. We also performed subgroup analyses considering the heterogeneity of the studies, including: type of exercise, frequency of training, cortisol measurement, and type of control group.


Systematic review

Study selection

At first, 463 studies were obtained in the search considering exercise, cortisol, and depression. Following application of the eligibility criteria, 24 studies were selected for full-text reading and review. After the selection procedure, five studies, with seven arms, were included in the meta-analysis. The selection process of the five studies25,26,29,30,39 included in this meta-analysis is showed in Figure 1.

Figure 1 Flowchart of study selection. 

Study characteristics

Overall, the five studies included 209 participants (125 intervention vs. 84 control subjects). Three of the five studies used clinical diagnosis based on DSM-IV or ICD-10 criteria, and the other two investigated depression using scales (GDS and CES-D). The mean age of the individual populations varied from 18.7±0.2 to 81.0±1.7 years old.

All the studies included were randomized controlled trials (Table 1). The duration of the intervention varied from 8 to 16 weeks for chronic studies. Different types of exercise were used, including aerobic exercise,25,29,30 jogging training,26 strength training,29 relaxation exercise,29 Buddhism walking meditation,37 traditional walking39 and stretching.25

Table 1 Summary of studies 

Study Sample characteristics MD characteristics Clinical diagnosis Exercise type Exercise methodology Exercise intensity Cortisol analysis Cortisol measurement Results
Foley et al.25 IG1 (n = 8), 18-55 years, male and female
CG (n = 5), 18-55 years, male and female
IG1: BDI-II 21.40±4.33 MADRS 28.80±9.86
IG2: BDI-II 20.00±7.08 MADRS 28.69±8.59
DSM-IV IG1: aerobic
IG2: stretching
3 days per week, 30/40 minutes (6 and 12 weeks) IG1: moderate IG2: mild Saliva Cortisol awakening response: awakening (T1), 30-minute post awakening (T2) and before bed (T3). Cortisol: ↓ IG1
DS: ↓ IG1
Nabkasorn et al.26 IG1 (n = 21), 18.7±0.2 years, female
CG (n = 28), 18.8±0.1 years, female
IG1: CES-D 20.1±0.9
IG2: CES-D 18.8±0.7
None IG1: jogging then usual routine
IG2: usual routine then jogging
IG1: 5 days per week, 50 minutes (8 weeks)
IG2: 8 weeks
Mild; constant HR of less than 50% of the HR reserve Urine 24 hours of excretions Cortisol: ↓ after exercise for IG1
DS: ↓ after exercise for IG1 and IG2
Krogh et al.29 IG1 (n = 29), 42.4±9.5 years, male and female
IG2 (n = 31), 39.3±9.8 years, male and female
CG (n = 28), 36.0±9.8 years, male and female
IG1: HAM-D 17.6±3.5
IG2: HAM-D 18.4±4.2
CG: HAM-D 15.6±3.4
ICD-10 IG1: strength
IG2: aerobic
CG: relaxation
2 days per week, 60 minutes (16 weeks) IG1: 50% of RM then 75% of RM
IG2: % HR maximum from 70 to 90%
Plasma Baseline (T1), post-intervention (T2) Cortisol: NS DS: NS
Carneiro et al.30 IG (n = 9), 18-65 years, female
CG (n = 10), 18-65 years, female
No scales ICD-10 IG: aerobic
CG: no exercise
3 days per week, 45/50 minutes (16 weeks) Average intensity, 72% HR maximum Plasma Baseline (T1) and after 16 weeks (T2) Cortisol: NS DS: -
Prakhinkit et al.37 IG1 (n = 13), 74.8±1.7 years, female
IG2 (n = 14), 74.0±1.9, female
CG (n = 13), 81.0±1.7, female
IG1: GDS 17.3±1.0
IG2: GDS 16.8±0.9
CG: GDS 17.9±0.7
None IG1: traditional walking
IG2: walking meditation
CG: sedentary group
P1 (IG1 and IG2): 3 days per week, 20 minutes (weeks 1-6)
P2 (IG1 and IG2): 3 days per week, 30 minutes (weeks 7-12)
P1 (IG1 and IG2): mild (20-39% HR reserve)
P2 (IG1 and IG2): moderate (40-50% HR reserve)
Plasma After 8 hours of overnight fasting Cortisol: ↓ IG2 DS: ↓ IG2

BDI = Beck Depression Inventory; CES-D = Center for Epidemiological Scale Depression; CG = control group; DS = depressive symptoms; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; GDS = Geriatric Depression Scale; HAM-D = Hamilton Depression Scale; HR = heart rate; ICD-10 = International Classification of Diseases; IG = intervention group; MADRS = Montgomery-Asberg Depression Rating Scale; MD = major depression; NS = nonsignificant; P = phase; RM = repetition maximum.

Exercise intensity was also different among the studies. One study assessing strength training investigated 75% of repetition maximum (RM),29 while the studies employing aerobic training used exercises of both high intensity29 (n = 1) and mild to moderate intensity (n = 4).25,26,30,39

Cortisol measurement was made in the saliva (n = 1),25 urine (n = 1),26 and plasma (n = 3)29,30,39 of the participants, at different times of the day. Cortisol assessments were also different among the studies. Two of them evaluated cortisol in basal condition,29,30 one article observed cortisol awakening response,25 another study assessed cortisol levels after 8 hours of overnight fasting39 and the last one measured 24 hours of excretions.26


Primary findings

There was a moderate favorable effect of exercise training on reduction of cortisol levels (SMD = −0.65; 95% confidence interval [95%CI] −1.30 to 0.01) (Figure 2).

Figure 2 Forest plot considering all the studies included in the meta-analysis. 

Risk of bias across studies

Visual analysis of the funnel plot showed asymmetry of two articles26,29 (three trials) within the studies, located outside the cone or as pseudo 95%CI. The plot is available in Online-Only Supplementary Figure 1.

Risk of bias within studies

Most studies included in this meta-analysis were classified as good quality (results available in Online-Only Supplementary Table 1.

Sensibility analysis

We performed a sensitivity analysis excluding the two trials that were located outside the funnel plot. The recalculated effect was equal to −0.64 (95%CI −1.17 to −0.10; I2 = 28.7) (Table 2).

Table 2 Subgroup meta-analyses 

Analysis SMD 95°CI p Heterogeneity I2 p
Main analysis (all trials) -0.65 -1.30 to 0.01 0.054 82.7 <0.001
Main analysis (four trials) -0.64 -1.17 to −0.10 0.019 28.7 0.240
Aerobic x strength
Aerobic -0.76 -1.55 to 0.03 0.059 83.9 <0.001
Strength -0.05 -0.57 to 0.47 0.842
5, 3 or 2 times per week
5 times per week -2.18 -2.90 to −1.47 <0.001
3 times per week -0.64 -1.17 to −0.10 0.019 28.7 0.240
2 times per week 0.05 -0.32 to 0.41 0.793 0.0 0.590
Saliva × plasma × urine
Saliva -0.88 -2.00 to 0.30 0.143
Plasma -0.26 -0.71 to 0.18 0.249 53.8 0.070
Urine -2.18 -2.90 to −1.47 <0.001
Control group types
Active treatment -0.05 -0.46 to 0.35 0.795 19.2 0.290
No treatment -0.99 -1.95 to −0.04 0.042 82.4 <0.001

95%CI = 95% confidence interval; SMD = standardized mean difference.

Subgroup analysis

Subgroup analyses are presented in Table 2. Significant reduction in cortisol levels was found for aerobic training (SMD = −0.76; 95%CI −1.55 to 0.03), while no effects were found for strength training (SMD = −0.05; 95%CI −0.57 to 0.47) (Online-Only Supplementary Figure 2).

A very large and significant reduction was found for exercising five times per week (SMD = −2.18; 95%CI −2.90 to −1.47), a moderate reduction for exercising three times per week (SMD = −0.64; 95%CI −1.17 to −0.10), and non-significant effects were found for exercising twice a week (SMD = 0.05; 95%CI −0.32 to 0.41) (Online-Only Supplementary Figure 3).

Regarding cortisol measurement, large effects were observed only for urine measurements (SMD = −2.18; 95%CI −2.90 to −1.47). Moderate but nonsignificant effects were found for cortisol measured in saliva (SMD = −0.88; 95%CI −2.06 to 0.30). Plasma measurement detected only a small reduction (SMD = −0.26; 95%CI −0.71 to −0.18) (Online-Only Supplementary Figure 4).

Finally, analysis of types of control groups revealed a trivial reduction of SMD when active treatment was used (SMD = −0.05; 95%CI −0.46 to 0.35), compared to a moderate reduction when the control group was not subjected to any treatment (SMD = −0.99; 95%CI −1.95 to −0.44) (Online-Only Supplementary Figure 5).


The current systematic review and meta-analysis aimed to synthesize the data available on cortisol changes after exercise training in individuals with MDD compared to control groups. A moderate reduction of cortisol levels was found following an exercise intervention in people with depression. However, these results should be interpreted cautiously due to the small number of studies and a substantial heterogeneity among them considering type of exercise, type of cortisol measurement, frequency of exercise, and type of control group.

Related to the type of exercise, the great majority of studies investigated aerobic exercise.25,26,29,30,39 Strength training29 and holistic exercise (walking meditation)39 were also evaluated. Although a higher effect was observed for aerobic training, this result did not reach statistical significance, probably due to the small number of articles included in this meta-analysis. Moreover, the results were divergent. One study29 observed non-significant reduction of cortisol after both aerobic and strength training. Another study30 also observed non-significant differences in cortisol levels. It is interesting to note that these studies investigated cortisol at baseline conditions. However, studies which have observed cortisol awakening response,25 morning cortisol after overnight fasting,39 and 24 hours of excretion through urine26 have found significant cortisol reductions. Since changes in diurnal rhythms of cortisol are well known to occur in some cases of MDD40 and can vary according to time of sampling,3 cortisol should be measured at different points of the day or in response to stimuli (awakening response or stressor) to produce remarkable results.

Another possible reason to explain the wide variability of the results is the type of specimen collection used to measure cortisol. Although a previous meta-analysis has concluded that this factor does not appear to impact the magnitude of change in cortisol levels pre- vs. post-treatment,41 we observed a very large effect for urine, following by a moderate effect for saliva and a small effect for plasma. Plasma measurement is a widely used method, however it is the most invasive form when compared to saliva and urine collections (i.e., a stressful procedure). It is possible that 24- hour urine measures have the advantage of providing integrative HPA axis measures over larger time periods. Nonetheless, compliance is poor for 24-hour measures, and renal conditions may affect urinary cortisol levels.42 In our meta-analysis, only one study evaluated this method.

Especially with regard to exercise methodology, the studies were also very discrepant, which may have impacted the results. For example, three different types of weekly frequencies were used: two,29 three25 and five times per week.26 In our study, a very large effect was found for training when the frequency was five times a week, whereas a moderate effect was present for three times a week and a small effect for two times a week. Other parameters should be considered, such as exercise intensity, which can impact the weekly calorie expenditure and promote greater effects in depressive symptoms.43 However, due to the heterogeneity of intensity measurement, we were not able to specifically evaluate dose response.

The variability of activities in the control groups was also an important methodological problem observed in the studies. For example, two studies25,29 investigated an active control group (stretching and relaxation, respectively), while three studies26,30,39 investigated a non-active control group. Our results indicate that a nonactive control group, without any type of intervention or exercise, yields larger effect sizes when compared with control groups also subjected to exercise, as an active control group can present changes in cortisol levels even with interventions that do not involve physical exercise, e.g. relaxation techniques. For example, two researches27,44 observed a significant reduction of cortisol levels using a deep breathing technique. Perhaps such holistic techniques can promote HPA changes through the reduction of negative cognitive and affective signals to the limbic system.22

Some limitations and strengths of the current metaanalysis should be considered. First, it is not possible to conclude that the effect of exercise on cortisol in individuals with MDD occurs concomitantly with reductions in depressive symptoms. Among the studies here evaluated, three showed significant reductions of depressive symptoms. However, one study did not present the association between reduced cortisol and improved depressive symptoms,30 and another found non-significant results.29 Second, our meta-analysis involved patients with a clinical diagnosis of depression and individuals with depressive symptoms according to depression scales. Due to the small number of articles included and the methodological differences among them, we cannot conclude if there was an influence of clinical diagnosis in the effect of exercise on cortisol levels. Finally, the small number of articles did not allow to reach a reliable conclusion regarding the subgroup analysis performed. Fortunately, most of the studies assessed in this meta-analysis were classified as good quality according to risk of bias within the studies. However, we assume that the quality of the trials published should be analyzed more cautiously.

Even though the findings of the present meta-analysis were not in accordance with the initial hypothesis, it is important to highlight that the modulation of cortisol in response to exercise training for depression needs to be investigated in more detail.

In conclusion, physical exercise promotes a moderate reduction in cortisol levels in MDD individuals. However, this finding can be influenced by methodological aspects, such as type of exercise, weekly frequency, and type of cortisol measurement.


Andrea Camaz Deslandes has received a fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; grant 301483/2016-7) and from Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ; grant E-26/203.193/2016).


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Received: December 20, 2017; Accepted: May 03, 2018

Correspondence: Ana Beserra Av. Venceslau Braz, 71, fundos, Botafogo 22290-140 - Rio de Janeiro, RJ - Brazil Tel.: +55 (21) 39385546 E-mail:


No conflicts of interest declared concerning the publication of this article.

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