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.

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.

The mode of bone conservation does not affect the architecture and the tensile properties of rat femurs.

The bone samples used in clinical and experimental trials must be the less damaged as possible to avoid alterations of their properties. However, the mode of storage might possibly alter the bone properties, particularly microarchitecture and strength. The aim of our study was to analyze the effects of deep-freezing and alcohol conservation techniques on the densitometric, microarchitectural and biomechanical parameters of rat femurs. The left femurs were elongated in uniaxial tension up to breakdown in order to calculate biomechanical parameters. The densitometric and microarchitectural properties of right femurs were evaluated using dual-energy X-ray absorptiometry and microcomputed tomography, respectively. Results showed no significant difference in the parameters investigated between deep-freezing, alcohol storage and fresh femurs when comparing each parameter separately. Therefore, one month storage in alcohol or deep-freezing seemed to induce no harmful effect on densitometric, microarchitectural and biomechanical parameters of rat femurs.

Alteration of trabecular bone under chronic beta2 agonists treatment.

PURPOSE: beta2 adrenergic agonists are widely used as doping agents. Their side effects on bone, especially microarchitecture, remain unknown. The purpose of this study was to evaluate the effects of chronic clenbuterol and salbutamol treatment on bones of growing rats. METHODS: Twelve-week-old Wistar female rats were divided into three groups: salbutamol (4 mg.kg(-1).d(-1)), clenbuterol (2 mg.kg(-1).d(-1)), and normal saline (0.5 mL.kg(-1).d(-1)) and treated for 6 wk. Proximal tibia and lumbar spine L4 were analyzed by absorptiometry and by 3D microcomputed tomography. Bending and compression tests were used to measure their mechanical properties. RESULTS: After 6 wk, the salbutamol and clenbuterol groups had lower bone mineral density (BMD) in the tibia, proximal tibia, and vertebrae. Trabecular number and bone volume for the vertebrae were lower in animals treated with clenbuterol (Tb.N: -14.31%, P < 0.001; BV/TV: -21.07%, P < 0.001) or salbutamol (TbN: -12.7%, P < 0.001; BV/TV: -19.7%, P < 0.001) than in controls. Mechanical properties of the tibia were affected by clenbuterol with a lower ultimate force (P = 0.02) and a trend in lower energy to ultimate force (P = 0.053). In vertebrae, salbutamol and clenbuterol induced lower ultimate force. Clenbuterol significantly increased muscle mass (+58.83%, P < 0.01) and reduced fat mass (-28.75%, P < 0.01) compared with controls +17.07 and -7.34%, respectively. CONCLUSION: This study shows a negative effect of clenbuterol and salbutamol on the mechanical properties and microarchitecture of trabecular bone. In the clenbuterol group it was notable that the bone loss contrasts with the anabolic effect on muscle mass. Clearly an increase of muscle mass with enhanced bone fragility augments the risk of fractures for humans or animals treated with beta2 agonists as part of a doping regimen.

Effects of long-term tennis playing on the muscle-bone relationship in the dominant and nondominant forearms.

The relationship between muscle strength and bone mineral density illustrates the positive effect of mechanical loading on bone. But local and systemic factors may affect both muscle and bone tissues. This study investigated the effects of long-term tennis playing on the relationship between lean tissue mass and bone mineral content in the forearms, taking the body dimensions into account. Fifty-two tennis players (age 24.2 +/- 5.8 yrs, 16.2 +/- 6.1 yrs of practice) were recruited. Lean tissue mass (LTM), bone area, bone mineral content (BMC), and bone mineral density were measured at the forearms from a DXA whole-body scan. Grip strength was assessed with a dynamometer. A marked side-to-side difference (p < 0.0001) was found in favor of the dominant forearm in all parameters. Bone area and BMC correlated with grip strength on both sides (r = 0.81-0.84, p < 0.0001). The correlations were still significant after adjusting for whole-body BMC, body height, or forearm length. This result reinforced the putative role of the muscles in the mechanical loading on bones. In addition, forearm BMC adjusted to LTM or grip strength was higher on the dominant side, suggesting that tennis playing exerts a direct effect on bone.