MS in Men and Women: The Role of Testosterone in Men

Patient Expert

In the post MS in Men vs. Women: Does Gender Matter?, we focused on the differences which are seen in the genders of people who develop MS.   Sex hormones play a significant role in differentiating the genders regardless of disease or health.   Today we're going to explore how hormones, specifically testosterone, affect men who develop MS.

Testosterone is a hormone which affects sexual features and development.   Men have about ten times more testosterone in their blood than women.   Yes, women do have testosterone which is produced by the ovaries, and both sexes have a small amount produced by the adrenal glands.

In males, testosterone levels are low before puberty, increase during puberty, peak around the age of 40, then gradually lessen as men age.   Coincidentally, or maybe not, men are diagnosed with MS more frequently just as their testosterone levels begin to drop.

Protection from MS
Testosterone seems to protect young men from developing MS.   Used therapeutically, it has a protective quality, inducing anti-inflammatory and neuroprotective effects.   A recent small pilot study involving 10 men with RRMS has supported this finding.   As the study used a crossover design, each patient served as his own control with a 6-month observation period followed by 12-months of treatment with gel containing 100mg testosterone (AndroGel ®) applied to the upper arms once per day.

Improving Outcomes
The results showed that one year of treatment with testosterone gel was associated with improvement in cognitive performance and slowing of brain atrophy.   Both very good findings.   However, there was no significant effect on gadolinium-enhancing lesions in number or quality.   Additionally, muscle mass was increased after the treatment period.   Based on the results, it is suggested that testosterone treatment is safe and well tolerated and has potential neuroprotective effects in men with relapsing-remitting MS.   This study did not include men with primary-progressive MS.

Immunomodulatory Effects
The same study explored the immunomodulatory effect which testosterone may exhibit as well.   Changes in specific cytokines and inflammatory markers were seen.   One change was "a shift in peripheral lymphocyte composition by a decrease of CD4+ autoreactive T-cells and an increase of NK (natural killer) cells."   Is that a good thing?

Interestingly, the study drug daclizumab treatment is also accompanied by a decrease of CD4+ cells and an increase of NK cells.   NK cells have been suggested to play a regulatory role by killing myelin-specific T-cells (which attack myelin) and immature dendritic cells, promoting regulatory T-cells and enhancing Th2-like responses.   Yes, these are good immunomodulatory responses.

Estrogen, Not Just for Women
Testosterone is converted to estrogen (estradiol) in the brain by the enzyme aromatase.   Several body building websites I read emphasize/hypothesize that too much of the enzyme increases estradiol levels and can cause low testosterone levels.   Remember that low serum levels seem to increase the risk of developing MS or increase its severity in men.

A study looking at several sex hormones and MRI features found that in men, a positive correlation was found between estradiol concentrations and brain damage on T1- and T2- weighted MRI scans.   T1 hypointense lesions ("black holes") indicate axonal loss and are strongly correlated with neurological disability in MS.   T2 hyperintense lesions can indicate various pathologies, ranging from edema and inflammation to demyelination and axonal loss.   Other sex hormone levels in men did not correlate significantly with tissue damage as seen on MRI.   Perhaps the good news was that EDSS disability scores and estradiol levels were not significantly associated.

In the next post, we will explore the role that the hormones testosterone and estriol have in women living with MS.

RESOURCES: Whitacre CC, Reingold SC, O'Looney PA, et at., Task Force on Gender, Multiple Sclerosis and Autoimmunity.   A Gender Gap in Autoimmunity, Supplementary Material.   Science, 1999 Feb 26;283(5406):1277-8.

Voskuhl RR. Gender issues and multiple sclerosis.   Curr Neurol Neurosci Rep, 2002 May;2(3):277-86.

Sicotte NL, Giesser BS, Tandon V, et al.   Testosterone Treatment in Multiple Sclerosis: A Pilot Study.   Arch Neurol, 2007;64(5):683-688.

Gold SM, Chalifoux, S, Giesser BS, Voskuh, RR. Immune modulation and increased neurotrophic factor production in multiple sclerosis patients treated with testosterone.   J Neuroinflammation, 2008;5:32.

Tomassini V, Onesti E, Mainero C, et al. Sex hormones modulate brain damage in multiple sclerosis: MRI evidence.   J Neurol Neurosurg Psychiatry, 2005;76:272-275.

More hormone/testosterone info can be found the Multiple Sclerosis Resource Centre website.