Sex Hormones as Key Modulators of the Immune Response in Multiple Sclerosis: A Review

Background: A variety of autoimmune diseases, including MS, amplify sex-based physiological differences in immunological responsiveness. Female MS patients experience pathophysiological changes during reproductive phases (pregnancy and menopause). Sex hormones can act on immune cells, potentially enabling them to modify MS risk, activity, and progression, and to play a role in treatment. Methods: Scientific papers (published between 1998 and 2021) were selected through PubMed, Google Scholar, and Web of Science literature repositories. The search was limited to publications analyzing the hormonal profile of male and female MS patients during different life phases, in particular focusing on sex hormone treatment. Results: Both men and women with MS have lower testosterone levels compared to healthy controls. The levels of estrogens and progesterone increase during pregnancy and then rapidly decrease after delivery, possibly mediating an immune-stabilizing process. The literature examined herein evidences the neuroprotective effect of testosterone and estrogens in MS, supporting further examinations of their potential therapeutic uses. Conclusions: A correlation has been identified between sex hormones and MS clinical activity. The combination of disease-modifying therapies with estrogen or estrogen plus a progestin receptor modulator promoting myelin repair might represent an important strategy for MS treatment in the future.