The Role of Androgens in Multiple Sclerosis: Promoting Myelin Regeneration and Reducing Inflammation in Women

2023-04-17 15:58:22

Multiple sclerosis (MS) affects three women for every one man. In its most common form, called relapsing-remitting (85% of cases), it results in inflammatory flare-ups during which the patient’s immune cells attack the myelin of the central nervous system and destroy it. This phenomenon leads to lesions that cause motor, sensory or visual disturbances. These symptoms are reversible at the onset of the disease, thanks to the spontaneous repair of the destroyed myelin. However, over time, they gradually become irreversible, which reflects the failure of the repair process and moves patients into the progressive phase of the disease.

Current research aims to better understand the mechanisms of the disease and to develop new therapeutic avenues which would prevent patients from entering the progressive phase, in particular by promoting the myelin regeneration.

Work has already shown that the androgens protect neurons in the central nervous system men patients with relapsing-remitting forms of multiple sclerosis and induce the regeneration of destroyed myelin sheaths in males, in animal models of the disease. But what is the role of the small amounts of androgens that are also found in the central nervous system of women? Androgens, present at much lower levels than in men, can they also have an impact on the progression of the disease in patients?

French researchers from the Inserm-University of Paris-Saclay unit “Diseases and Hormones of the Nervous System” have worked with animal models of MS but also from patient tissues from organ donation banks. They first showed that in regions where myelin is destroyed, the AR receptor that allows androgens to transmit their signal is strongly expressed in the nervous tissue of women with multiple sclerosis, as in that of female mice used as disease models. Although only present in small quantities in females, androgens have an action promoting optimal regeneration of destroyed myelin : in fact, when the signals transmitted by androgens are blocked, this regeneration is greatly reduced.

These same androgens also have major anti-inflammatory effects in the demyelinated nervous tissue of females. The beneficial effects of androgens in women with multiple sclerosis might therefore also be linked to the reduction in the level of local inflammation, in areas where myelin is destroyed. This result is all the more interesting since, according to the current hypothesis, the progression of the disease might be closely associated with the inflammatory cells residing in the nervous tissue.

Thus, contrary to what one might think, and despite their low concentration, these results suggest that male hormones play a neuroprotective, anti-inflammatory and remyelinating role in women with multiple sclerosis.

« Our data suggests the use of appropriate doses of androgens in women patients with multiple sclerosis and the need to take the patient’s gender into consideration in the therapeutic approach to this pathology “, concludes Elisabeth Traiffort, author of the study.

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