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Testosterone therapy and the pathogenesis of Kennedy's disease (X-linked bulbospinal muscular atrophy).
Journal of the Neurological Sciences 1996 Februrary
The mutation in X-linked bulbospinal muscular atrophy (XBSMA) is an increased CAG triplet repeat coding for a polyglutamine domain in the gene for the androgen receptor. This might impair the effect of testosterone on motor neurons, leading to their progressive degeneration. We report a trial of high-dose oral testosterone therapy in two brothers with XBSMA. Patient 1 received 37.5 mg of testosterone daily for more than 18 months, and Patient 2 received 25 mg per day for six months, both in combination with exercise therapy. Patient 1 showed improvement of up to 300% in muscle work output. Patient 2, who did less exercise, had no symptomatic improvement. These results indicate that exogenous testosterone therapy is not harmful, and may produce functional improvement when combined with exercise. We hypothesize that high-dose testosterone may reduce a toxic gain of function that the mutation produces, perhaps by inhibiting glutamate neurotoxicity.
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