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Male sex hormone testosterone shows nerve-protecting capabilities in mice with MS-like disease

November 6, 2012

Researchers funded by the National MS Society have shown that the male sex hormone testosterone prevented or restored impairments in nerve impulse transmission in mice with EAE, an MS-like disease. The improvements specifically occurred in an area of the brain associated with cognitive function, lending evidence to the potential for the future use of sex hormones to treat this MS symptom. This team is currently conducting clinical  trials to determine whether estriol (another sex hormone, added on to standard therapies) improves disease activity and cognition in women with MS. Rhonda Voskuhl, MD (University of California, Los Angeles) and colleagues report their findings in The Journal of Neuroscience (2012;32:12312).

Background: Sex hormones may contribute to MS susceptibility and ongoing disease activity by influencing the immune attack on brain and spinal cord tissues. Laboratory studies have shown that the severity of EAE, an MS-like disease, is decreased when testosterone, a male sex hormone, is administered to male and female mice. Dr. Voskuhl was awarded funding from the National MS Society’s targeted research initiative on Gender Differences in MS to undertake a small study of testosterone gel in men with MS. One year of treatment with a gel containing the sex hormone testosterone (applied to the skin) in 10 men with relapsing-remitting multiple sclerosis resulted in significant improvements in cognitive function and in slowing brain tissue loss, indicating possible neuroprotective effects. (Archives of Neurology 2007;64:683).

In separate studies, this team also has found evidence in MS of tissue loss in an area of the brain called the hippocampus, a region deep in the brain known to be important in cognitive function. (Brain 2008;131:1134). Now, they are studying how testosterone treatment may affect the hippocampus, for clues to understanding its potential for treating cognitive function.

The Study: Dr. Voskuhl’s team administered testosterone or inactive placebo to mice before and after inducing EAE, an MS-like disease. Using tests that measure electrical conduction, they found that the disease specifically impaired nerve impulse transmission in the hippocampus. Treatment with testosterone before inducing EAE prevented impaired to some extent nerve impulse transmission. Treatment after the disease began reduced signs of disease and restored proper nerve impulse transmission.

Comment: This study lends further evidence to the potential for the use of sex hormones to treat MS and in particular, cognitive issues. This team is currently conducting two clinical trials of estriol (another gender hormone, added on to standard therapies): one, funded by the National MS Society and NIH, involves 150 women with MS and is testing whether estriol can slow disease course and activity; the other involves 64 women with MS and is testing whether the hormone improves cognition.

The authors note the testosterone may be neuroprotective like estrogens because it converts to estrogen in the body. “Both sex hormones should be considered as candidate treatments to improve cognition during MS.”

About Multiple Sclerosis

Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system. Symptoms range from numbness and tingling to blindness and paralysis, and there is currently no cure for MS. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are leading to better understanding and moving us closer to a world free of MS. An estimated 1 million people live with MS in the United States. Most people with MS are diagnosed between the ages of 20 and 50, and it affects women three times more than men.


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