Patients with severe chronic obstructive pulmonary disease (COPD) commonly develop weight loss, muscle wasting, and consequently poor survival. Nutritional supplementation and anabolic steroids increase lean body mass, improve muscle strength, and survival in patients enrolled in comprehensive rehabilitation programs. Whether anabolic steroids are effective outside an intensive rehabilitation program is not known. We conducted a prospective, double-blind, placebo-controlled, 16-week trial to study the benefits of anabolic steroids in patients with severe COPD who did not participate in a structured rehabilitation program. Biweekly intramuscular injections of either the drug (nandrolone decanoate) or placebo were administered. Sixteen patients with severe COPD were randomized to either placebo or nandrolone decanoate. The placebo group weighed 55.32 +/- 11.33 kg at baseline and 54.15 +/- 10.80 kg at 16 weeks; the treatment group weighed 68.80 +/- 6.58 at baseline and 67.92 +/- 6.73 at 16 weeks. Lean body mass remained unchanged, 71 +/- 6 vs. 71 +/- 7 kg in placebo group and 67 +/- 7 vs. 67 +/- 7 in treatment group, at baseline and 16 weeks respectively. The distance walked on 6 min was unchanged at baseline, 8 weeks, and 16 weeks in placebo (291.17 +/- 134.83, 282.42 +/- 115.39, 286.00 +/- 82.63 m) and treatment groups (336.13 +/- 127.59, 364.83 +/- 146.99, 327.00 +/- 173.73 m). No improvement occurred in forced expiratory volume in one second, forced vital capacity, maximal inspiratory pressure, maximal expiratory pressure, VO(2) max or 6-min walk distance or health related quality of life. Administration of anabolic steroids (nandrolone decanoate) outside a dedicated rehabilitation program did not lead to either weight gain, improvement in physiological function, or better quality of life in patients with severe COPD.