Doping Status of DHEA Treatment for Female Athletes with Adrenal Insufficiency.

OBJECTIVE: To review the doping status of dehydroepiandrosterone (DHEA) for female athletes with adrenal insufficiency within the framework of Therapeutic Use Exemption (TUE) applications for this proandrogen, which is included on the World Anti-Doping Agency (WADA)'s Prohibited List. DATA SOURCES AND MAIN RESULTS: Current knowledge of adrenal pathophysiology with a focus on the physiological role and pharmacological effects of DHEA in female athletes including placebo-controlled clinical trials of DHEA and consensus clinical practice and prescribing guidelines. CONCLUSIONS: Because there is no convincing clinical evidence to support the use of DHEA replacement therapy in women with adrenal failure, a TUE for DHEA is not justified by definite health benefit for either secondary or primary adrenal failure. This is consistent with the 2014 update of the US Endocrine Society guidelines, meta-analyses of DHEA treatment in women with or without adrenal failure, current WADA TUE guidance document for adrenal insufficiency and recent case law of WADA's Court of Arbitration for Sport.

The decrease in mature myostatin protein in male skeletal muscle is developmentally regulated by growth hormone.

Myostatin inhibits myogenesis and there is reduced abundance of the mature protein in skeletal muscles of adult male compared with female mice. This reduction probably occurs after translation, which suggests that it is a regulated mechanism to reduce the availability of myostatin in males. Reduced myostatin may, thereby, contribute to the development of sexually dimorphic growth of skeletal muscle. Our first objective was to determine if the decrease in mature myostatin protein occurs before the linear growth phase to aid growth, or afterwards to maintain the mass of adult muscle. Mice were killed from 2 to 32 weeks and the gastrocnemius muscle was excised. Myostatin mRNA increased from 2 to 32 weeks and was higher in males than females (P < 0.001). In contrast, mature protein decreased in males after 6 weeks (P < 0.001). Our second objective was to determine if growth hormone (GH) induces the decrease in mature myostatin protein. GH increased myostatin mRNA and decreased the abundance of mature protein in hypophysectomised mice (P < 0.05). Our final objective was to determine if the decrease in mature protein occurs in skeletal muscles of male Stat5b(-/-) mice (Stat5b mediates the actions of GH). As expected, mature myostatin protein was not reduced in Stat5b(-/-) males compared with females. However, myostatin mRNA remained higher in males than females irrespective of genotype. These data suggest that: (1) the decrease in mature myostatin protein is developmentally regulated, (2) GH acting via Stat5b regulates the abundance of mature myostatin and (3) GH acts via a non-Stat5b pathway to regulate myostatin mRNA.

Manual physical therapy and exercise versus electrophysical agents and exercise in the management of plantar heel pain: a multicenter randomized clinical trial.

STUDY DESIGN: Randomized clinical trial. OBJECTIVE: To compare the effectiveness of 2 different conservative management approaches in the treatment of plantar heel pain. BACKGROUND: There is insufficient evidence to establish the optimal physical therapy management strategies for patients with heel pain, and little evidence of long-term effects. METHODS: Patients with a primary report of plantar heel pain underwent a standard evaluation and completed a number of patient self-report questionnaires, including the Lower Extremity Functional Scale (LEFS), the Foot and Ankle Ability Measure (FAAM), and the Numeric Pain Rating Scale (NPRS). Patients were randomly assigned to be treated with either an electrophysical agents and exercise (EPAX) or a manual physical therapy and exercise (MTEX) approach. Outcomes of interest were captured at baseline and at 4-week and 6-month follow-ups. The primary aim (effects of treatment on pain and disability) was examined with a mixed-model analysis of variance (ANOVA). The hypothesis of interest was the 2-way interaction (group by time). RESULTS: Sixty subjects (mean [SD] age, 48.4 [8.7] years) satisfied the eligibility criteria, agreed to participate, and were randomized into the EPAX (n = 30) or MTEX group (n = 30). The overall group-by-time interaction for the ANOVA was statistically significant for the LEFS (P = .002), FAAM (P = .005), and pain (P = .043). Between-group differences favored the MTEX group at both 4-week (difference in LEFS, 13.5; 95% CI: 6.3, 20.8) and 6-month (9.9; 95% CI: 1.2, 18.6) follow-ups. CONCLUSION: The results of this study provide evidence that MTEX is a superior management approach over an EPAX approach in the management of individuals with plantar heel pain at both the short- and long-term follow-ups. Future studies should examine the contribution of the different components of the exercise and manual physical therapy programs. LEVEL OF EVIDENCE: Therapy, level 1b.

Effects of indomethacin and celecoxib on renal function in athletes.

INTRODUCTION: Strenuous exercise induces a marked reduction in renal hemodynamics. Prostaglandins (PG) play an important role in maintaining renal integrity in the face of hemodynamic changes. Inhibition of cyclooxygenase (COX) and thus PG formation can further compromise renal perfusion. The role of selective COX-2 inhibition on renal hemodynamics during exercise has not been investigated. METHODS: Twelve healthy males (22-47 yr) took part in a randomized placebo controlled study investigating the effects of nonselective COX inhibition (indomethacin) and COX-2 selective inhibition (celecoxib) on renal hemodynamics during exercise. Renal blood flow (RBF), glomerular filtration rate (GFR), and free water clearance were measured using standard clearance techniques. Each experimental session was performed at least a week apart. The medications were taken for 36 h before study with the last dose at 0700 h on the day of study. Following baseline studies, each participant exercised for 30 min at 80% of their maximal aerobic power. Renal function was monitored for 2 h post-recovery. RESULTS: RBF and GFR fell by 40% after exercise with no significant difference between placebo, indomethacin, or celecoxib. Indomethacin (-2.43 +/- 0.95 mL x min(-1), P < 0.007) and celecoxib (-3.88 +/- 0.94 mL x min(-1), P < 0.0001) significantly reduced free water clearance compared with placebo during recovery. CONCLUSION: This study has confirmed that selective and nonselective COX inhibition can induce significant inhibition of free water clearance, indicating that these acute changes are regulated predominantly via COX-2. Acute cerebral edema with hyponatremia has been reported after major endurance sporting events. Identifiable risk factors include excessive hydration and use of NSAID. Impaired free water clearance during exercise potentiated by COX inhibition provides a pathophysiological explanation for these observations.

Changes in fat mass and fat-free mass during the adiposity rebound: FLAME study.

OBJECTIVE: To determine the changes in body composition from 3 to 7 years of age in children undergoing adiposity rebound (AR) at different ages. METHODS: Body composition was measured bi-annually by bioelectrical impedance in 229 children from a birth cohort. Age at AR was calculated from changes in weight and height velocity over time. Early AR was defined as < 6.1 years (boys) and < 5.6 years (girls). Differences in fat mass (FM) and fat-free mass (FFM) and the velocity of change in these measures were calculated between early and late rebounders. Physical activity (accelerometry), time in sedentary activity, birth factors, and parental weight were compared. RESULTS: Children with early and late AR did not differ in body composition at 3 years of age, except for greater FFM in boys (by 0.8 kg, P = 0.022). In both sexes, change in body mass index (BMI) was significantly higher in early compared with late AR, and was entirely due to differences in the rate of weight gain, rather than any discrepancy in height velocity. This weight differential is predominantly due to increased deposition of FM in girls and FFM in boys. However, in both sexes, children with early rebound have significantly greater increases in FM velocity from 5 years of age. Few differences in any environmental influences were observed. CONCLUSIONS: Variation in BMI associated with the timing of AR is due to differences in weight rather than height, and sex differences in the relative contribution of FM and FFM to this additional weight gain are apparent.

Longitudinal study of physical activity and inactivity in preschoolers: the FLAME study.

PURPOSE: To investigate patterns of activity and inactivity in a birth cohort of children followed from 3 to 5 yr and to investigate whether changes in activity occurred over time. METHODS: Two hundred and forty-four children (44% female) were seen annually at 3, 4, and 5 yr. Physical activity and inactivity was measured by questionnaire (parent-proxy) and by Actical accelerometers for five consecutive days (24-h monitoring) each year in children and once in each parent for 7 d (69% with data). RESULTS: Retention of participants was high (92%). Viable accelerometry data were obtained for 76-85% of children at each age. Reliability estimates ranged from 0.80 (3 yr) to 0.84 (5 yr). Day of the week, season, sex, hours of childcare, or birth order did not affect daily average accelerometry counts (AAC) at any age. Parental activity correlated weakly with the child's activity at 3 and 4 yr (r values = 0.17-0.28), but only the father's activity remained a significant predictor of the child's activity after adjustment for confounders. Children spent approximately 90 min.d in screen time (television, videos, DVD, and computers) with an additional 90 min in other sedentary activities (reading, drawing, and music). Physical activity was significantly reduced at 4 and 5 yr compared with 3 yr in both sexes, whether measured as AAC (24-h data, awake time only, weekend days, weekdays), time in moderate or vigorous activity, or from parental reports of activity. CONCLUSION: Levels of physical activity declined in boys and girls between the ages 3 and 4-5 yr, whether using objective measures or parental reports of activity.

Exercise can be pyrogenic in humans.

Exercise increases mean body temperature (T(body)) and cytokine concentrations in plasma. Cytokines facilitate PG production via cyclooxygenase (COX) enzymes, and PGE(2) can mediate fever. Therefore, we used a COX-2 inhibitor to test the hypothesis that PG-mediated pyrogenicity may contribute to the raised T(body) in exercising humans. In a double-blind, cross-over design, 10 males [age: 23 yr (SD 5), Vo(2 max): 53 ml x kg(-1) x min(-1) (SD 5)] consumed rofecoxib (50 mg/day; NSAID) or placebo (PLAC) for 6 days, 2 wk apart. Exercising thermoregulation was measured on day 6 during 45-min running ( approximately 75% Vo(2 max)) followed by 45-min cycling and 60-min seated recovery (28 degrees C, 50% relative humidity). Plasma cytokine (TNF-alpha, IL-10) concentrations were measured at rest and 30-min recovery. T(body) was similar at rest in PLAC (35.59 degrees C) and NSAID (35.53 degrees C) and increased similarly during running, but became 0.33 degrees C (SD 0.26) lower in NSAID during cycling (37.39 degrees C vs. 37.07 degrees C; P = 0.03), and remained lower throughout recovery. Sweating was initiated at T(body) of approximately 35.6 degrees C in both conditions but ceased at higher T(body) in PLAC than NSAID during recovery [36.66 degrees C (SD 0.36) vs. 36.39 degrees C (SD 0.27); P = 0.03]. Cardiac frequency averaged 6 x min(-1) higher in PLAC (P < 0.01), whereas exercising metabolic rate was similar (505 vs. 507 W x m(-2); P = 0.56). A modest increase in both cytokines across exercise was similar between conditions. COX-2 specific NSAID lowered exercising heat and cardiovascular strain and the sweating (offset) threshold, independently of heat production, indicating that PGE-mediated inflammatory processes may contribute to exercising heat strain during endurance exercise in humans.