We have studied the effect of a pharmacological dose of testosterone enanthate (3 mg.kg-1.wk-1 for 12 wk) on muscle mass and total-body potassium and on whole-body and muscle protein synthesis in normal male subjects. Muscle mass estimated by creatinine excretion increased in all nine subjects (20% mean increase, P less than 0.02); total body potassium mass estimated by 40K counting increased in all subjects (12% mean increase, P less than 0.0001). In four subjects, a primed continuous infusion protocol with L-[1-13C]leucine was used to determine whole-body leucine flux and oxidation. Whole-body protein synthesis was estimated from nonoxidative flux. Muscle protein synthesis rate was determined by measuring [13C]leucine incorporation into muscle samples obtained by needle biopsy. Testosterone increased muscle protein synthesis in all subjects (27% mean increase, P less than 0.05). Leucine oxidation decreased slightly (17% mean decrease, P less than 0.01), but whole-body protein synthesis did not change significantly. Muscle morphometry showed no significant increase in muscle fiber diameter. These studies suggest that testosterone increases muscle mass by increasing muscle protein synthesis.

Variability in corticosteroid use suggests uncertainty about risks/benefits of corticosteroid regimens for DMD.

These studies provide Class I evidence that DCP significantly reduces attack frequency in HOP but lacked the precision to support either efficacy or lack of efficacy of DCP in HYP.

Key PointsQuestionWhat is the difference in clinical outcomes among 3 corticosteroid regimens (0.75 mg/kg of daily prednisone, 0.90 mg/kg of daily deflazacort, or 0.75 mg/kg of intermittent prednisone for 10 days on and then 10 days off) as initial treatment for boys with Duchenne muscular dystrophy?FindingsThis randomized clinical trial included 196 boys with Duchenne muscular dystrophy; the clinical outcome was a global outcome that incorporated a measure of rising from the floor, forced vital capacity, and global satisfaction with treatment assessed over 3 years. Daily prednisone and daily deflazacort resulted in significantly better outcomes compared with intermittent prednisone; there was no significant difference between the 2 daily regimens.MeaningThe findings support the use of a daily corticosteroid regimen over an intermittent prednisone regimen that alternates dosing for 10 days on and 10 days off as initial treatment for boys with Duchenne muscular dystrophy.

Despite corticosteroids being the only treatment documented to improve strength and function in boys with Duchenne muscular dystrophy (DMD) corticosteroid prescription is inconsistent and in some countries, corticosteroids are not prescribed. We are conducting a clinical trial that (1) compares the 3 most frequently prescribed corticosteroid regimes; (2) standardizes treatment of DMD complications; and (3) standardizes prevention of corticosteroid side effects. Investigators at 38 sites in 5 countries plan to recruit 300 boys aged 4–7 who are randomly assigned to one of three regimens: daily prednisone; daily deflazacort; or intermittent prednisone (10 days on/10 days off). Boys are followed for a minimum of 3 years to assess the relative effectiveness and adverse event profiles of the different regimens. The primary outcome is a 3-dimensional variable consisting of log-transformed time to rise from the floor, forced vital capacity, and subject/parent satisfaction with treatment, each averaged over all post-baseline visits. The study protocol includes evidence- and consensus-based treatment of DMD complications and of corticosteroid side effects. This study seeks to establish a standard corticosteroid regimen for DMD. Since all new interventions for DMD are being developed as add-on therapies to corticosteroids, defining the optimum regimen is of importance for all new treatments.