A role for anabolic steroids in the rehabilitation of patients with COPD? A double-blind, placebo-controlled, randomized trial.
OBJECTIVE
Skeletal muscle weakness commonly occurs in patients with COPD. Long-term use of systemic glucocorticosteroids further contributes to muscle weakness. Anabolic steroids could be an additional mode of intervention to improve outcome of pulmonary rehabilitation by increasing physiologic functioning, possibly mediated by increasing erythropoietic function.


METHODS
We randomly assigned 63 male patients with COPD to receive on days 1, 15, 29, and 43 a deep IM injection of 50 mg of nandrolone decanoate (ND) [Deca-Durabolin; N.V. Organon; Oss, The Netherlands] in 1 mL of arachis oil, or 1 mL of arachis oil alone (placebo) in a double-blind design. All patients participated in a standardized pulmonary rehabilitation program. Outcome measures were body composition by deuterium and bromide dilution, respiratory and peripheral muscle function, incremental exercise testing, and health status by the St. George's Respiratory Questionnaire.


RESULTS
Treatment with ND relative to placebo resulted in higher increases in fat-free mass (FFM; mean, 1.7 kg [SD, 2.5] vs 0.3 kg [SD, 1.9]; p = 0.015) owing to a rise in intracellular mass (mean, 1.8 kg [SD, 3.1] vs - 0.5 kg [SD, 3.1]; p = 0.002). Muscle function, exercise capacity, and health status improved in both groups to the same extent. Only after ND were increases in erythropoietic parameters seen (erythropoietin: mean, 2.08 U/L [SD, 5.56], p = 0.067; hemoglobin: mean, 0.29 mmol/L [SD, 0.73], p = 0.055). In the total group, the changes in maximal inspiratory mouth pressure (PImax) and peak workload were positively correlated with the change in hemoglobin (r = 0.30, p = 0.032, and r = 0.34, p = 0.016, respectively), whereas the change in isokinetic leg work was correlated with the change in erythropoietin (r = 0.38, p = 0.013). In the patients receiving maintenance treatment with low-dose oral glucocorticosteroids (31 of 63 patients; mean, 7.5 mg/24 h [SD, 2.4]), greater improvements in PImax (mean, 6.0 cm H(2)O [SD, 8.82] vs - 2.18 cm H(2)O [SD, 11.08], p = 0.046), and peak workload (mean, 20.47 W [SD, 19.82] vs 4.80 W [SD, 7.74], p = 0.023) were seen after 8 weeks of treatment with ND vs placebo.


CONCLUSIONS
In conclusion, a short-term course of ND had an overall positive effect relative to placebo on FFM without expanding extracellular water in patients with COPD. In the total group, the improvements in muscle function and exercise capacity were associated with improvements in erythropoietic parameters. The use of low-dose oral glucocorticosteroids as maintenance medication significantly impaired the response to pulmonary rehabilitation with respect to respiratory muscle function and exercise capacity, which could be restored by ND treatment.
Creutzberg
Eva C
EC
Department of Pulmonology, University Hospital Maastricht, Maastricht, The Netherlands. E.Creutzberg@PUL.Unimaas.NL
Wouters
Emiel F M
EF
Mostert
Rob
R
Pluymers
Rob J
RJ
Schols
Annemie M W J
AM
D000368:Aged; D045930:Anabolic Agents / Q000008:administration & dosage*; D001823:Body Composition; D004311:Double-Blind Method; D004920:Erythropoiesis; D017079:Exercise Tolerance; D006304:Health Status; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D018908:Muscle Weakness / Q000188:drug therapy / Q000209:etiology; D018482:Muscle, Skeletal / Q000503:physiopathology; D009277:Nandrolone / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000077603:Nandrolone Decanoate; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000150:complications / Q000503:physiopathology / Q000534:rehabilitation*; D012132:Respiratory Muscles / Q000503:physiopathology
D045930:Anabolic Agents; D009277:Nandrolone; D000077603:Nandrolone Decanoate