Reducing testosterone levels in a large-scale trial in men with spinal-bulbar muscular atrophy (SBMA, or Kennedy disease) did not significantly affect swallowing function, despite earlier indications that it might improve this aspect of the disease.
Difficulty swallowing can be a major problem in SBMA, which is caused by a mutation in the androgen receptor gene on the X chromosome. The mutation causes the androgen receptor protein to become toxic when it interacts with androgens (male hormones, such as testosterone). As a result of this toxic interaction, muscle-controlling nerve cells called motor neurons gradually die, leading to weakness of the arms, legs, face, tongue, throat and jaw.
About the new findings
Reducing testosterone levels with leuprorelin, an injectable drug used to treat prostate cancer, was tried as a treatment for SBMA, in an attempt to reduce the toxic combination of abnormally formed androgen receptors with androgen hormones.
In an earlier, smaller trial conducted in Japan, there was some indication that reducing testosterone with leuprorelin improved swallowing function in men with SBMA.
Gen Sobue at Nagoya (Japan) University Graduate School of Medicine, and colleagues, published the new findings online Aug. 4, 2010, in Lancet Neurology.
In the new study, 204 Japanese SBMA patients were randomly assigned to receive either a leuprorelin injection or an injection of a placebo every 12 weeks.
At the end of 48 weeks, those on leuprorelin did not show significant effects on swallowing function compared to those who received the placebo, although the drug was well tolerated.
Trial participants had received SBMA diagnoses ranging from four months to 38 years prior to the trial. Investigators suggest that patients with a shorter disease duration might fare better with anti-testosterone treatment than those with disease of long duration. They also say more sensitive measures of swallowing and other disease characteristics might be needed to accurately measure anti-testosterone treatment effects more accurately.
Although the investigators judged leuprorelin to be "well tolerated," they also saw deterioration in measurements of quality of life in those taking the drug. "The mental, emotional, and physical aspects of quality of life are lower in men who have had androgen deprivation treatment, including leurprorelin, probably because of hormonal imbalance and drug-related depression," they note.
Meaning for people with SBMA
The investigators say the results of this trial are not definitive and that their findings should be validated in other settings and in patients from other ethnic backgrounds.
However, given leuprorelin's lack of benefit for swallowing function and its negative effects on quality of life, there may not be much interest in further investigation of this drug for SBMA.