On the heels of a large-scale clinical trial now underway to confirm that the female hormone estriol combats the effects of multiple sclerosis in women, a recently completed UCLA pilot study shows promise for the use of testosterone to combat the effects of the disease in men.
Reporting in the May issue of the journal Archives of Neurology, Dr. Rhonda Voskuhl, director of UCLA's Multiple Sclerosis Program, and her colleagues found that the application of a testosterone gel reduced symptoms, slowed brain degeneration and increased muscle mass in men with relapsing-remitting multiple sclerosis, the most common form of the disease. Testosterone also has been shown to protect against an MS-like condition in animals.
Multiple sclerosis is a progressive disease involving the immune and central nervous systems. Like many other autoimmune diseases, in which the body attacks its own systems or tissues, MS is less common in men than in women, said Voskuhl, with a ratio of about three women to one man. Voskuhl has long thought that sex hormones and/or sex chromosomes may be responsible for this enhanced susceptibility.
Voskuhl and Dr. Nancy L. Sicotte, UCLA assistant professor of neurology, conducted a study of testosterone treatment in 10 men with relapsing-remitting MS, which is characterized by periods of neurologic symptoms, such as numbness or difficulty walking, followed by periods of remission. After enrollment in the study, the men, whose average age was 46, entered a six-month pre-treatment phase, during which symptoms were monitored but no therapies were administered. After that, each man applied 10 grams of a gel containing 100 milligrams of testosterone to his upper arms once daily for 12 months.
"After a year, we saw an improvement in cognitive performance and a slowing of brain deterioration," Voskuhl said. In fact, during the final nine months of gel application, the rate of brain deterioration in the men slowed by 67 percent.
In addition, the men's muscle mass increased an average of 1.7 kilograms, about 3.74 pounds, during the treatment phase. There were no reported adverse effects.
"The other optimistic thing about this study was that the protective effect of testosterone treatment on brain atrophy was observed in the absence of an appreciable anti-inflammatory effect," said Voskuhl, "which suggests the protection the testosterone provided may not be limited to MS but may be applicable to other non-inflammatory neurodegenerative diseases, such as Parkinson's or Alzheimer's disease."
Four years ago, Voskuhl conducted a pilot study in which 10 women with MS were given the female hormone estriol, which yielded what she described as "pretty remarkable" results — an 80 percent drop in inflammatory lesions in the brain, which are a hallmark of the disease. That led to the much larger trial now underway. Her goal now is to expand the testosterone pilot study into a much larger clinical trial.
"Overall, the use of the testosterone gel treatment in men with MS was shown to be safe and well-tolerated," she said. "In addition, our exploratory findings suggest there's a possible neuroprotective effect of testosterone treatment in men, which we feel warrants a larger study."
The UCLA Department of Neurology encompasses more than a dozen research, clinical and teaching programs. These programs cover brain-mapping and neuroimaging, movement disorders, Alzheimer's disease, multiple sclerosis, neurogenetics, nerve and muscle disorders, epilepsy, neuro-oncology, neurotology, neuropsychology, headaches and migraines, neurorehabilitation, and neurovascular disorders. The department ranked No. 1 among its peers nationwide in National Institutes of Health funding in 2005. For more information, visit .
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Mark Wheeler
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