Androgen Reduction Has Few Benefits for SBMA


Major Finding: Men with spinal and bulbar muscular atrophy who were treated with dutasteride for 2 years had significantly better physical quality of life, but significantly worse mental quality of life, than did placebo-treated patients. No differences in muscle strength were found.

Data Source: A phase II, randomized, double-blind, placebo-controlled trial of 50 men

Disclosures: The trial was funded by the National Institute of Neurological Diseases and Stroke. None of the investigators had relevant disclosures.

BALTIMORE — Long-term dutasteride therapy in men with spinal and bulbar muscular atrophy does not appear to improve muscle strength or fatigue and might actually lower mental quality of life, according to the results of a phase II, randomized, double-blind, placebo-controlled trial.

Patients derived some benefit from treatment with the 5-alpha reductase inhibitor, which converts testosterone into more potent dihydrotestosterone, as a result of a significant reduction in their number of falls and improvement in their physical quality of life.

Spinal and bulbar muscular atrophy (SBMA) is characterized by a toxic buildup of mutant androgen receptors with an excessively long string of glutamine residues in motor neurons. This buildup weakens bulbar and extremity muscles, causing difficulty with gait and dysphagia, and also might lead to gynecomastia, infertility, and other manifestations of androgen insensitivity. Dutasteride has been thought to be a potential therapy for SBMA because experiments in mice that were bred to express the mutant androgen receptor showed that reducing androgen levels could mitigate the toxicity of the mutant phenotype.

To evaluate the efficacy and safety of dutasteride (Avodart), Dr. Kenneth H. Fischbeck, chief of the Neurogenetics Branch of the National Institute of Neurological Diseases and Stroke and his colleagues randomized 50 men with SBMA to either 0.5 mg/day of dutasteride or placebo. That dose of dutasteride is the same as that approved for treating symptomatic benign prostatic hyperplasia.

The men in each group were an average age of about 53 years, and had an average CAG repeat length of 4 codons (compared with wild-type human repeat length of 36 codons or less), a mean duration of weakness of about 12 years, and an average body mass index of about 28 kg/m

After 2 years, patients treated with dutasteride had virtually no appreciable increase in weight-scaled quantitative muscle assessment scores from baseline—the primary efficacy measure—whereas the scores in patients taking placebo declined by 5% from baseline. This difference was not significant, according to the investigators, who reported their results in a poster session at the annual meeting of the American Neurological Association.

On the Short Form–36 quality of life questionnaire (version 2), the physical component summary improved by about 14% from baseline for dutasteride-treated patients, which was significantly different from the 10% drop recorded in placebo-treated patients.

Significantly fewer falls occurred among patients who were treated with dutasteride than among those who received placebo (9 patients reporting 40 falls vs. 16 subjects reporting 63 falls).

However, patients who took dutasteride fared more poorly than those who took placebo on the mental component summary of the questionnaire, in which patients on placebo had a 10% improvement and patients on dutasteride worsened by about 7%.

Modified barium swallow scores, a measurement for dysphagia severity, worsened by a similar amount in subsets of patients from both arms.

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