Ana Milošević, Marija M Janjic, Dunja Dimitrijevic, Ivana Bjelobaba
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, mostly occurring during the reproductive period, and it is diagnosed more frequently in women. The sex biases in the incidence and course of both MS and its most commonly used animal model, experimental autoimmune encephalomyelitis (EAE), seem to be driven by fluctuations in sex hormones. The regulation of sex hormone synthesis and release relies on a dynamic hierarchical system-the hypothalamic-pituitary-gonadal (HPG) axis. This review provides an overview of the main characteristics of MS and EAE pathologies and explains the structure and function of the HPG axis in order to better understand the sex-specific features of MS and EAE. The particular role of sex hormones as culprits in the sex differences in these pathologies is covered, as well as the disturbances to the HPG axis that arise as a consequence of MS/EAE course. Finally, the use of sex hormones as potential adjuvant therapeutics for MS is discussed. Given the complexity and dynamism in the regulation of the HPG axis, an individual, holistic approach should be taken when considering sex hormones for the treatment of MS patients.