Why does MS occur significantly more often in women than in men? – I am often asked this question. There is no clear answer to this, but the question has led to some interesting research activities in recent years, which have contributed to a further understanding of the disease.
The phenomenon of a higher prevalence in women can be observed in many autoimmune diseases – not only in MS, but also in rheumatoid arthritis or systemic lupus erythematosus, women are preferred sufferers.
Multiple sclerosis affects women 3 – 4 times more often than men and it seems as if the ratio would continue to increase. Hormonal factors are probably responsible for this. On the other hand, different gene expressions of receptor molecules in female brains have also been discovered in recent years. For example, it was recently reported that the receptor S1PR2, which plays a role in the incorporation of immune cells into the brain, is more strongly expressed in female (MS) brains.
However, it is currently assumed that sexual hormones in particular play a role in the complex interactions between environmental factors (sunlight, vitamin D), genetic and epigenetic influences(MHC risk alleles) and cultural factors (urbanization, female education), and influence MS risk and disease progression.
For example, women with MS show an earlier onset of disease compared to men and have more inflammatory lesions on MRI. On the other hand, men have a worse prognosis than women, show faster progression and often suffer from cerebellar involvement. There are also gender-related differences in cognition – the male sex is considered a predictor of poorer cognitive performance. In line with this observation, men also show a more pronounced atrophy of the gray matter and have more hypointense T1 lesions.
The reasons for these gender-specific differences are not clear, but it is obvious that they are based on hormonal differences. A strong argument for the influence of sex hormones is that the differences in disease progression between women and men level off again after menopause. Since estrogen, the female sex hormone, has been shown to have neuroprotective effects in animal tests, it is conceivable that women generally possess better repair mechanisms.
Interestingly, environmental factors, which are attributed an importance for the development of MS, also have different effects on men and women. Vitamin D seems to have a greater immunomodulatory effect in women with MS than in men. In an animal experiment, only female mice that were fed a vitamin D enriched diet had a milder course of disease.
Since the function of hormones includes immune modulation and neuroprotection in addition to classic communication between organs, understanding their effect provides another possibility for controlling autoimmune diseases. This can result in a therapeutic use of hormones, for which some studies have already been conducted, or in the therapeutic use of pregnancy-related tolerance-inducing factors. On the other hand, a better understanding can also be important with regard to personalized, gender-specific therapy.
