We recently reported increased leg lean mass and strength in men with chronic obstructive pulmonary disease (COPD) receiving 10 weeks of testosterone (T) and leg resistance training (R) (Casaburi R, Bhasin S, Cosentino L, et al. Am J Respir Crit Care Med. 2004;170:870-878). This study evaluates the role of muscle insulin-like growth factor (IGF) and related factors as potential mechanisms for our findings using quadriceps muscle biopsies from the same cohort. Patient groups were on (1) weekly placebo (P) injections + no R; (2) P and R; (3) weekly injections of T + no R; and (4) T + R (TR). Muscle fibers were classified histochemically, and their cross-sectional areas (CSAs) and fiber density (number of fibers per unit area) were determined. Gene transcripts were determined by real-time PCR and protein expression by radioimmunoassay. While no significant changes in fiber CSAs were noted across groups, increased trends were observed after 10 weeks, and significant decrements in muscle fiber density were noted in all treated groups. A global increase in all myosin heavy chain (MyHC) mRNA isoforms was observed in TR patients. Muscle IGF-IEa and IGF-IEc mRNAs were significantly increased with TR group. Muscle IGF-I protein was increased in all intervention groups (greatest in TR). While TR IGF-II mRNA was increased, protein levels were unaltered. IGF binding protein-4 mRNA was increased with TR. Myogenin mRNA was increased in both T groups, whereas MyoD and myostatin were unchanged. Muscle atrophy F-box mRNA tended to increase with TR. Our data suggest that the combined interventions produced an enhanced local anabolic milieu driven in large part by the muscle IGF system despite potentially negative biochemical influences present in COPD patients

Editor's Comments. While public debate on the pros and cons of anabolic steroids roils the world of professional sport, evidence continues to accumulate in their favor in clinical situations where muscle mass, strength, and function are demonstrably impaired. The recent joint ACCP/AACVPR pulmonary rehabilitation guidelines (Ries et al. Chest. 2007;131;4-42) correctly states that the evidence in favor is insufficient to support their clinical use, but this is more a reflection of inadequate data than the presence of compelling negative studies. On the contrary, data continue to accumulate which point toward a consistent increase in lean muscle mass and accompanying strength. What remains lacking is evidence that this leads to an improvement in exercise capacity or other meaningful outcomes such as an improved quality of life. In addition, legitimate concerns remain about the safety of androgenic agents, especially in older men. Until these are more fully addressed, anabolic steroids will continue to be frequently discussed but rarely used as components of an exercise or a rehabilitation program.-SK