A Rational Approach on the Use of Sex Steroids in Multiple Sclerosis

Multiple sclerosis (MS) is a demyelinating disease in which myelin autoreactive T cells drive a chronic inflammatory process leading to myelin destruction. A sexual dimorphism has been described, with prevalence in females and a better clinical course during pregnancy. Specific receptors have been identified for sex steroids in the cytoplasm of immune and neural cells. Experimental autoimmune encephalomyelitis (EAE), the most frequently studied animal model for MS, showed sex differences in the disease course and improvement by the use of exogenous sex steroids. The recent pilot studies in vivo also reported an improvement of MS by the administration of gonadal hormones (replacement therapy, testosterone, estriol) in the short time. A patent proposed estriol therapy to treat autoimmune related disorders (including MS). A clinical European trial is ongoing on the use of nomegestrol/estradiol in the post-partum period in order to prevent the relapses. Integrated therapies appear to be effective in both male and female MS patients.