Does Testicular Hypofunction Lower Multiple Sclerosis Risk in Men?

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Several lines of evidence indicate that gender affects the susceptibility and course of MS with a higher disease prevalence and overall better prognosis in women.

Several lines of evidence indicate that gender affects the susceptibility and course of multiple sclerosis (MS) with a higher disease prevalence and overall better prognosis in women than in men. This sexual dimorphism may be explained by the effects of sex steroid hormones.

Pakpoor and colleagues¹ used a large UK dataset to see whether testicular hypofunction (as a proxy for low testosterone levels) was associated with lower MS risk in males.

The study used data from the English Hospital Episode Statistics (HES), which collects data on admissions to hospitals in England for the country’s entire population (about 50 million people). Admissions are given a diagnostic code, and a person’s hospital admissions can be linked together over time (termed record-linkage).

In this study, the researchers had data on hospital admissions between 1999 and 2011. They identified males initially admitted for testicular hypofunction and then assessed their subsequent risk of being admitted for MS compared with males initially admitted for minor acute conditions.

Overall, the risk of being admitted for MS in people with testicular hypofunction, relative to those without, was 4.62 (95% confidence interval, 2.30 to 8.24).

This study has many limitations because of using routinely collected health care data. It has few data on potential confounders and, importantly, hospital admissions are used as a proxy for diagnosis.

However, the study is interesting, as a previous pilot trial of testosterone gel to treat men with relapsing-remitting MS showed enhanced cognitive function and delayed brain gray matter atrophy in patients after 1 year of treatment. Testosterone supplementation might be a low-cost, low-risk, and high-benefit management strategy in MS.

How low testosterone levels may act to influence MS risk remains speculative. Future work will need to investigate directly the possible relationship between low testosterone levels and MS risk and, if true, the mechanism behind it.