Testosterone is associated with worse disease severity in men with early relapsing onset multiple sclerosis

November 1, 2013 Peiqing Qian, M.D.

MS and many other autoimmune diseases are less common in men than in women. This is especially true during reproductive years. Sex hormones, including testosterone and estrogen, may be responsible for the difference. It is thought that men with multiple sclerosis may have lower testosterone levels than healthy controls.

Dr. Bove and his group assessed the prevalence and clinical associations of hypogonadism in men with recent onset relapsing multiple sclerosis.  Male subjects from the Comprehensive Longitudinal Investigations of MS at the Brigham and Women's Hospital (CLIMB) cohort were included. Hormonal measures included testosterone, the testosterone: estradiol ratio, leutinizing hormone (LH), and free testosterone. Clinical outcomes were collected every 6 months for Expanded Disease Severity Scale (EDSS), and annually for Symbol Digit Modalities test (SDMT).

The analysis included 96 men with a mean age of 40 years, disease duration of 4.6 years; 71% subjects were untreated at baseline. Of these men, 39% were hypogonadal (with morning total testosterone levels below 288 ng/dL); none showed appropriate compensatory elevations in LH. In the primary cross-sectional analyses, there was a negative age-adjusted correlation between total testosterone and EDSS. Similar clinical associations were noted for the testosterone:estradiol ratio and for free testosterone.  In the primary age-adjusted longitudinal analyses, higher baseline testosterone levels were associated with fewer declines in cognitive function test like SDMT. 

This study indicates there is a high prevalence of hypogonadotropic hypogonadism in men with recent relapsing-onset MS. Low testosterone levels may be associated with worse clinical outcomes.  A small pilot study suggests that testosterone treatment may be safe, well tolerated and may reduce symptoms, slow brain degeneration and increase muscle mass in men with relapsing-remitting multiple sclerosis.  Further studies are merited to determine whether testosterone plays a neuroprotective role in men with MS or whether it is a marker for disease severity.

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