The effects of androgen therapy on neuromuscular disorders have been best studied by Griggs et al. in a series of careful studies of myotonic dystrophy (MD), a genetic myopathy due to a trinucleotide (CTG) repeat mutation in the myotonin (protein kinase) gene. MD is associated with testicular atrophy and biochemical androgen deficiency compared with age-matched healthy men or men with other neuromuscular wasting diseases (Griggs etal. 1985), although serum testosterone does not correlate with extent of muscle wasting. Since life expectancy in MD is determined by respiratory muscular weakness leading to terminal pneumonia, androgen therapy aiming to improve muscular strength might prolong life. To test this hypothesis, a randomised placebo-controlled study was undertaken in 40 men with MD who were treated with either testosterone enanthate (3 mg/kg) or placebo injections each week for 12 months (Griggs etal. 1989). In a well-designed two-site study, muscle mass was increased as indicated by creatinine excretion and total body potassium, but there was no difference in quantitative measures of manual or respiratory muscle strength. Crucially, the lack of improved pulmonary function implies that mortality benefits would be unlikely. Androgen therapy may simply increase the mass of dysfunctional muscle.
The same investigators also examined the effect of androgen therapy in boys with Duchenne muscular dystrophy (DMD) in a randomised placebo-controlled study (Fenichel etal. 2001) following encouraging results from an uncontrolled pilot study of ten boys treated for three months (Fenichel et al. 1997). Boys aged 5-10 years of age with DMD (n = 51) were randomly assigned to receive oxandrolone (0.1 mg/kg/day) or placebo for six months. Although the primary endpoint (semi-quantitative average muscle strength score) and timed functional tests of gait were not significantly improved, oxandrolone produced a significant increase in some post-hoc comparisons such as quantitative myometry and in upper limb muscle strength score. The marginal efficacy of oxandrolone was accompanied by proportionate growth and few side effects so that such treatment may find a role before instituting high dose glucocorticoids, which are more effective but also cause more adverse effects including growth retardation and weight gain.
The discrepancy between these findings is puzzling and the precise role of pharmacological androgen therapy in other forms of neurogenetic or degenerative neuromuscular disorders warrants further evaluation.
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