January 6th, 2004
Boston Cure Project
One possible reason why fewer men than women get MS is that male sex hormones such as testosterone help protect against the disease. This also fits with the observation that onset in men typically occurs in their 30's, when hormone levels start to decline. A group of researchers at UCLA explored this possibility by examining the role of testosterone in mice with EAE (an experimental animal disease with features similar to MS). Using a strain of mice that has a gender bias in EAE (females more susceptible than males), they removed the sex organs from half the mice while giving the rest "sham" operations that left the organs intact. After allowing the mice a little time to recover, they then performed the steps to induce EAE.
They found that the castrated (male) mice developed a more severe form of EAE than the intact males, while the ovariectomized (female) mice were affected no differently from the intact females. This indicates that the gender bias in this strain of mice is likely due to protection provided by the male sex hormones, as opposed to a risk increase provided by the female hormones. They then administered supplemental testosterone in intact males, both in this strain and in another genetic strain of mice in which castration did not boost the severity. In both strains, the supplemental testosterone decreased the severity of EAE. These results have led to a pilot clinical trial of supplemental testosterone in men with MS.
Interestingly, another recent study from the University of Illinois also found that castration in a particular strain of mice increased the severity of EAE. However, in this study, removal of the ovaries did have a clinical effect, increasing the severity but shortening the duration of the disease. This is a good reminder that genetic differences play a large role in disease susceptibility and clinical outcome, and genetic heterogeneity among humans will likewise probably affect the influence of sex hormones in MS.
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