Neuroprotection from Testosterone

How believable is the data hinting that testosterone has neuroprotective effects? #MSBlog #MSResearch

"At first glance this small exploratory trial of testosterone in men produces some interesting data and suggests it is neuroprotective in men with MS. Problems? The variability of MRI brain atrophy typically requires 60-80 subjects per arm in a 2 year study to discern a meaningful outcome. 10 subjects in an 18 month study (6 month baseline vs. 12 month treatment) is far too small to be confident this is a real effect. I larger parallel group study is required (~80 per arm for 2 years). Please note that testosterone replacement therapy is not without risks; it is associated with an increased risk of prostate cancer, vascular disease (myocardial infarction and stroke) and hypertension to name a few. Therefore it may be very difficult to get this study past the regulatory authorities and ethics committees. The side effect profile makes this an unexciting treatment to take forward in MS. In addition, the treatment strategy is only targeting males and not the majority of MSers who are female."

Kurth et al. Neuroprotective effects of testosterone treatment in men with multiple sclerosis. Neuroimage Clin. 2014;4:454-60.

Background: MS is an inflammatory and neurodegenerative disease of the central nervous system. While current medication reduces relapses and inflammatory activity, it has only a modest effect on long-term disability and gray matter atrophy. 

Objective: Here, we have characterized the potential neuroprotective effects of testosterone on cerebral gray matter in a pilot clinical trial. 

Methods: Ten men with relapsing–remitting MS were included in this open-label phase II trial. Subjects were observed without treatment for 6 months, followed by testosterone treatment for another 12 months. Focal gray matter loss as a marker for neurodegeneration was assessed using voxel-based morphometry. 

Results: During the non-treatment phase, significant voxel-wise gray matter decreases were widespread (p≤ 0.05 corrected). However, during testosterone treatment, gray matter loss was no longer evident. In fact, a significant gray matter increase in the right frontal cortex was observed (p≤ 0.05 corrected). 

Conclusions: These observations support the potential of testosterone treatment to stall (and perhaps even reverse) neurodegeneration associated with MS. Furthermore, they warrant the investigation of testosterone's neuroprotective effects in larger, placebo controlled MS trials as well as in other neurodegenerative diseases. This is the first report of gray matter increase as the result of treatment in MS

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