Hormonal and gender-related immune changes in multiple sclerosis

Similarly to many other autoimmune diseases, multiple sclerosis (MS) is more common among women than men, and its incidence among women is rising. There are also qualitative differences in the disease course between men and women, with male patients experiencing increased disease progression, brain atrophy, and cognitive impairment. During pregnancy, women with MS typically have a greatly reduced relapse rate, whereas very soon after the delivery, the disease activity returns, often even at a higher level than seen in the prepregnancy year. The reasons for the increased postpartum activity are not entirely clear, but factors such as the abrupt decrease in estrogen levels immediately after the delivery and the loss of the immunosuppressive state of pregnancy are likely of importance. There is compelling evidence that estrogen, progesterone, and testosterone control MS pathology by influencing immune responses and by contributing to repair mechanisms in the nervous system. Hormones may thus offer important insights into MS disease prevention and treatment. In this review, the possible reasons for the sex bias in autoimmune diseases will be discussed. The pregnancy-related alterations in MS, including the effect of pregnancy on disease activity, long-term disability accumulation, and prevalence will be reviewed, as well as the hormonal and immunological mechanisms potentially underlying these changes. Finally, the present thinking on the effect of hormones on the changing incidence of MS will be elucidated.