Chronic obstructive lung disease

Advanced chronic airflow limitation is associatedwith weight loss and muscle depletion, possibly due to the increased energy requirements required for breathing or reduced serum testosterone concentrations (Kamischke etal. 1998). Interventions aimed at improving muscle bulk such as nutrition, exercise or androgens may therefore have an impact on the morbidity and/or mortality of the underlying respiratory disease. One large well-conducted prospective study demonstrated that short-term low-dose androgen therapy (nandrolone decanoate) augmented the effects of nutritional supplementation in patients with moderate to severe chronic airways disease (Schols et al. 1995). From 233 consecutive patients with stable, moderate to severe and bronchodilator-unresponsive pulmonary disease admitted to an intensive pulmonary rehabilitation program, 217 were randomised into three groups. These were to receive eight weeks of treatment with (a) placebo injections, (b) a nutritional supplement (one high fat, high calorie drink daily) plus placebo injections or (c) a nutritional supplement plus androgen injections (nandrolone decanoate [50 mg men, 25 mg women]) with intramuscular injections given fortnightly. Participants were also stratified according to the degree ofbaseline muscle depletion (body weight <90% and/or lean mass <67% ideal ornot) at entry. During the study all patients underwent a standardised exercise program. Both nutrition and androgen therapy increased body weight over placebo, with androgen therapy having more prominent effects on lean body mass and respiratory muscle strength although there was no measurable improvement in submaximal exercise tolerance nor any major adverse effects. The lack of an androgen-alone arm and blinding with respect to nutritional supplementation made it difficult to evaluate the impact of androgen therapy relative to improved nutrition. After 4 years, follow-up of 203 of these men revealed no treatment effect on survival (Schols etal. 1998); however in a post hoc analysis, those with larger increases in weight (including 24% of the initial placebo group) had a significantly decreased mortality risk. More recently, a longer term study examining the effect of androgen supplementation without nutritional supplements has been reported (Ferreira et al. 1998). In this study, 23 undernourished men with COPD undergoing progressive pulmonary rehabilitation were randomised to receive additionally androgen (testosterone esters 250 mg intramuscularly for one injection followed by stanozolol 12 mg/day) or placebo for 27 weeks. No effect on respiratory muscle strength or endurance exercise capability was detected despite significant increases in lean body mass.

It is important to recognise that improvement in underlying pulmonary disease itself may ameliorate the gonadal dysfunction of systemic disease. In one study of men with chronic obstructive pulmonary disease with severe hypoxia and impotence, long-term oxygen therapy improved total and free testosterone and lowered SHBG (without changes in LH or FSH) in five men who had improved sexual function. The remaining seven who had unimproved sexual function had no changes in circulating hormone concentrations (Aasebo etal. 1993).

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