Glucocorticoid administration in athletes: Performance, metabolism and detection.

It is generally acknowledged in the sporting world that glucocorticoid (GC) use enhances physical performance. This pharmacological class is therefore banned by the World Anti-Doping Agency (WADA) in in-competition samples after systemic but not local (defined as any route other than oral, intravenous, intramuscular or rectal) administration, which thus allows athletes to use GCs for therapeutic purposes. According to the 2016 WADA list, the urine reporting level for all GCs is set at 30ng/ml to distinguish between the authorized and banned routes of administration. The actual data on the ergogenic effects of GC intake are nevertheless fairly recent, with the first study showing improved physical performance with systemic GC administration dating back only to 2007. Moreover, the studies over the last decade coupling ergogenic and metabolic investigations in humans during and after GC intake have shown discrepant results. Similarly, urine discrimination between banned and authorized GC use remains complex, but it seems likely to be improved thanks to new analytical studies and the inclusion of the authorized GC uses (local routes of administration and out-of-competition samples) in the WADA monitoring program. In this review, we first summarize the current knowledge on the ergogenic and metabolic GC effects in humans during various types of exercise. We then present the antidoping legislation and methods of analysis currently used to detect GC abuse and conclude with some practical considerations and perspectives.

Short-term glucocorticoid intake improves exercise endurance in healthy recreationally trained women.

The present study investigated whether short-term oral administration of glucocorticoid would modify performance and selected hormonal and metabolic parameters during submaximal exercise in healthy women. Nine recreational female athletes completed cycling trials at 70-75% VO(2) max until exhaustion after either placebo (Pla, gelatin) or oral prednisone (Cor, Cortancyl, 50 mg per day for 1 week) treatment, according to a double-blind and randomized protocol. Blood samples were collected at rest; after 10, 20, and 30 min of exercise; at exhaustion; and after 10 and 20 min of passive recovery for adrenocorticotrophic hormone (ACTH), dehydroepiandrosterone (DHEA), prolactin (PRL), growth hormone (GH), insulin (Ins), blood glucose (Glu), and lactate (Lac) determination. Cycling time was significantly increased with short-term Cor intake (Cor: 66.4 +/- 8.4 vs. Pla: 47.9 +/- 6.7 min, P < 0.01). ACTH and DHEA remained completely blunted throughout the experiment with Cor versus Pla (P < 0.01), whereas GH and PRL were significantly decreased with Cor after, respectively, 20 and 30 min of exercise (P < 0.05). No significant difference in Ins or Glu values was found between the two treatments but Lac concentrations were significantly increased with Cor versus Pla between 10 and 30 min of exercise (P < 0.05). These data indicate that short-term glucocorticoid intake improved endurance performance in women, but further investigation is needed to determine whether these results are applicable to elite female athletes and, if so, current WADA legislation needs to be changed.

The vastus lateralis neuromuscular activity during all-out cycling exercise.

OBJECTIVE: The objective of this work was to study modifications in motor control through surface electromyographic (sEMG) activity during a very short all-out cycling exercise. METHODS: Twelve male cyclists (age 23+/-4 years) participated in this study. After a warm-up period, each subject performed three all-out cycling exercises of 6s separated by 2 min of complete rest. This protocol was repeated three times with a minimum of 2 days between each session. The braking torque imposed on cycling motion was 19 Nm. The sEMG of the vastus lateralis was recorded during the first seven contractions of the sprint. Time-frequency analysis of sEMG was performed using continuous wavelet transform. The mean power frequency (MPF, qualitative modifications in the recruitment of motor units) and signal energy (a quantitative indicator of modifications in the motor units recruitment) were computed for the frequency range 10-500 Hz. RESULTS: sEMG energy increased (P0.05) between contraction number 1 and 2, decreased (P < or =0.05) between contraction number 2 and 3 then stabilized between contraction number 3 and 7 during the all-out test. MPF increased (P < or =0.05) during the all-out test. This increase was more marked during the first two contractions. CONCLUSIONS: The decrease in energy and the increase in the sEMG MPF suggest a large spatial recruitment of motor units (MUs) at the beginning of the sprint followed by a preferential recruitment of faster MUs at the end of the sprint, respectively.

Effects of short-term prednisolone intake during submaximal exercise.

PURPOSE: To examine the prednisolone's ergogenic and metabolic effects during submaximal exercise. METHODS: Ten recreational male athletes completed two cycling trials at 70-75% peak O2 consumption until exhaustion after either placebo (Pla, lactose) or oral prednisolone (Pred, 60 mg.d(-1) for 1 wk) treatment, according to a double-blind and randomized protocol. Blood samples were collected at rest and during exercise and recovery to determine ACTH, growth hormone (GH), prolactin (PRL), DHEA, insulin, blood glucose, and blood lactate values. RESULTS: Time of cycling was significantly increased after chronic Pred treatment (Pred: 74.5+/-9.5 min; Pla: 46.1+/-3.3 min, P<0.01). Pred intake significantly lowered basal, exercise, and recovery ACTH, DHEA, and PRL concentrations, whereas GH concentrations were significantly lowered by Pred after 30 min of exercise. Blood glucose and insulin were significantly (P<0.05) increased by Pred during the whole experiment and until 30 min of exercise. Blood lactate concentrations were higher after Pred versus Pla at 10 min of exercise until 10 min of recovery (P<0.05). CONCLUSION: From these data, short-term Pred intake did seem to significantly improve performance during submaximal exercise, with concomitant alterations in hormonal and metabolic responses. Further studies will be necessary to elucidate the mechanisms of these hormonal and metabolic changes, and to determine whether the changes may be associated with the marked performance improvement obtained.

Effects of acute salbutamol intake during supramaximal exercise in women.

OBJECTIVE: To study the effects of an acute therapeutic oral intake of beta(2) agonist on performance and substrate response during supramaximal exercise in women. METHODS: 12 healthy moderately trained female volunteers performed a Wingate test after ingestion of placebo (Pla) and salbutamol (Sal; 4 mg) according to a double-blind randomised crossover study. Blood samples were collected at rest, at the end of exercise and after 5 (r5), 10 (r10) and 15 (r15) min of passive recovery for adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin, blood glucose and lactate measurements. RESULTS: Peak power (PP) and mean power (MP) significantly increased whereas time to peak power was significantly shorter with Sal than with Pla (p<0.05). No change was observed in the fatigue index. ACTH was not significantly modified but r15 growth hormone significantly decreased (p<0.05) after the intake of Sal. Both blood INS and blood glucose were significantly increased by the intake of Sal during all the experiments (p<0.01). Blood lactate was significantly increased by the intake of Sal compared with that of Pla (p<0.05) after 10 and 15 min of passive recovery. CONCLUSION: From these data, acute therapeutic oral intake of Sal seems to induce, irrespective of the subjects' gender, an improvement in performance during a supramaximal exercise--that is, increase in PP and MP. Further studies are necessary to clarify whether the mechanisms involved in the response to intake of Sal are linked to central and/or peripheral pathways.

Dynamic responses of oxygen uptake at the onset and end of moderate and heavy exercise in trained subjects.

Inconsistencies about dynamic asymmetry between the on- and off-transient responses in VO2 are found in the literature. Therefore the purpose of this study was to examine VO2 on- and off-transients during moderate- and heavy-intensity cycling exercise in trained subjects. Ten men underwent an initial incremental test for the estimation of ventilatory threshold (VT) and, on different days, two bouts of square-wave exercise at moderate (VT) intensities. VO2 kinetics in exercise and recovery were better described by a single exponential model (VT). For moderate exercise, we found a symmetry of VO2 kinetics between the on- and off-transients (i.e., fundamental component), consistent with a system manifesting linear control dynamics. For heavy exercise, a slow component superimposed on the fundamental phase was expressed in both the exercise and recovery, with similar parameter estimates. But the on-transient values of the time constant were appreciably faster than the associated off-transient, and independent of the work rate imposed (VT). Our results do not support a dynamically linear system model of VO2 during cycling exercise in the heavy-intensity domain.

(.)VO(2) and EMG activity kinetics during moderate and severe constant work rate exercise in trained cyclists.

The purpose of this study was to compare O(2) uptake ((.)VO(2)) and muscle electromyography activity kinetics during moderate and severe exercise to test the hypothesis of progressive recruitment of fast-twitch fibers in the explanation of the VO(2) slow component. After an incremental test to exhaustion, 7 trained cyclists (mean +/- SD, 61.4 +/- 4.2 ml x min(-1) x kg(- 1)) performed several square-wave transitions for 6 min at moderate and severe intensities on a bicycle ergometer. The (.)VO(2) response and the electrical activity (i.e., median power frequency, MDF) of the quadriceps vastus lateralis and vastus medialis of both lower limbs were measured continuously during exercise. After 2 to 3 min of exercise onset, MDF values increased similarly during moderate and severe exercise for almost all muscles whereas a (.)VO(2) slow component occurred during severe exercise. There was no relationship between the increase of MDF values and the magnitude of the (.)VO(2) slow component during the severe exercise. These results suggest that the origin of the slow component may not be due to the progressive recruitment of fast-twitch fibers.

Influence of body composition, hemoglobin concentration, and cardiac size and function of gender differences in maximal oxygen uptake in prepubertal children.

OBJECTIVE: To determine the relative contribution of the gender difference in body composition, blood hemoglobin concentration, and cardiac dimension and function at rest and exercise of the gender difference in maximal oxygen uptake (O(2)max) in 10- to 12-year-old children. SUBJECTS: Thirty-five healthy children (17 girls and 18 boys; mean +/- SD age, 10.5 +/- 0.4 years). EXPERIMENTAL DESIGN: An anthropometric evaluation (body surface area, body fat content, and lean body mass [LBM]), assessment of hemoglobin concentration, echocardiographic evaluation at rest (left ventricular dimensions, and diastolic and systolic indexes at rest), and cardiovascular evaluation during a maximal cycle exercise (stroke volume [SV], total peripheral resistance). RESULTS: The boys exhibited a higher mass-relative O(2)max than the girls (47.9 mL/kg/min vs 40.9 mL/kg/min, respectively); but when normalized for LBM (allometric equation), the difference totally disappeared (19.0 mL/kg LBM(1.33)/min vs 18.9 mL/kg LBM(1.33)/min, respectively). No significant gender differences were seen in maximal heart rate and arteriovenous oxygen difference; however, maximal SV (SVmax) was significantly higher in boys than in girls, but when expressed relative to LBM, the difference was no longer significant. CONCLUSIONS: These findings demonstrate that contrary to adults, the sole limiting factor of O(2) that distinguished boys from girls was a lower SVmax in the latter; however, this gender difference totally disappeared when normalized for LBM. Consequently, the gender difference in heart size and cardiac function during exercise should be interpreted as only one aspect of the lower LBM in girls and not as reflective of a more basic functional gender difference.

Dynamic responses of O2 uptake at the onset and end of exercise in trained subjects.

Inconsistencies about dynamic asymmetry between the on- and off-transient responses in .VO2 are found in the literature. Therefore the purpose of this study was to examine .VO2on- and off-transients during moderate- and heavy-intensity cycling exercise in trained subjects. Ten men underwent an initial incremental test for the estimation of ventilatory threshold (VT) and, on different days, two bouts of square-wave exercise at moderate (VT) intensities. .VO2 kinetics in exercise and recovery were better described by a single exponential model (VT). For moderate exercise, we found a symmetry of .VO2 kinetics between the on- and off-transients (i.e., fundamental component), consistent with a system manifesting linear control dynamics. For heavy exercise, a slow component superimposed on the fundamental phase was expressed in both the exercise and recovery, with similar parameter estimates. But the on-transient values of the time constant were appreciably faster than the associated off-transient, and independent of the work rate imposed (VT). Our results do not support a dynamically linear system model of .VO2 during cycling exercise in the heavy-intensity domain.

Left ventricular dynamics during early recovery from maximal exercise in boys and men.

UNLABELLED: A transient increase in left ventricular emptying has been reported in adults during the early recovery from submaximal upright exercise. PURPOSE: To investigate whether this "overshoot" occurs also after maximal exercise, and whether it is an age-related phenomenon. METHODS: Ten healthy young men (mean age: 22.5 +/- 1.5 yr) and 17 healthy prepubertal boys (11.5 +/- 0.8 yr) performed an upright cycle test until exhaustion. Respiratory gas exchange, heart rate, left ventricular dimensions (two-dimensional echocardiography method) as well as blood pressures (manual sphygmomanometry) were assessed and systemic vascular resistances were calculated at rest, during the final minute of the test, and during a 10-min recovery period. RESULTS: An improvement of cardiac emptying, characterized by a decrease in left ventricular end-systolic diameter, was observed in adults only. Moreover, during the first minute of recovery, a larger decrease in heart rate -21.8 +/- 7.6% and -13.7 +/- 6.3 beat.min, respectively, in children and adults, P < 0.01) and a larger increase in systemic vascular resistance (+24.1 +/- 18.2% and +6.4 +/- 12.6%, P < 0.05) were observed in the boys rather than in the adults. CONCLUSION: Our results suggest that a higher increase in cardiac afterload and a more prominent decrease in heart rate may be responsible in part for the absence of cardiac overshoot in children.

Central and peripheral cardiovascular adaptations during a maximal cycle exercise in boys and men.

PURPOSE: Stroke volume response to exercise depends on changes in cardiac filling, intrinsic myocardial contractility, and left ventricular afterload. The purpose of this study was to compare these responses during an upright cycle test performed until exhaustion in children and adults. METHODS: Stroke volume, cardiac output (Doppler echocardiography), left ventricular dimensions (two-dimensional and time-movement echocardiography), as well as arterial pressure and systemic vascular resistance (SVR) were assessed in 17 boys (mean age, 11.7 +/- 0.6 yr) and 23 young adult men (mean age, 21.2 +/- 2.7 yr) having a similar aerobic potential. All variables were measured at the end of the resting period, during the final minute of each workload, and during the last minute of the test. RESULTS: No significant differences were obtained for stroke volume, cardiac output, and left ventricular dimensions when they were scaled to body surface area at rest and whatever the exercise intensity. However, arteriovenous oxygen uptake was higher and the SVR lower in the adults than in the children. CONCLUSION: The patterns of stroke volume, as well as its underlying mechanisms, were not age-related during an upright maximal exercise test. However, other studies are required to understand further the effect of pubertal status on the peripheral cardiovascular system.