Anastasiya G. Trenova

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/63630

#### **Abstract**

Experimental and clinical data about the influence of sex hormones on the course of multiple sclerosis (MS) grow rapidly during the past two decades. Estrogens, proges‐ terone, and androgens have been shown to ameliorate experimental autoimmune encephalomyelitis (EAE) in animals, and pregnancy in women is associated with a dramatic reduction in disease activity. Immunomodulatory and neuroprotective properties of sex hormones are the most probable underlying mechanisms, creating a background for testing similar hormonal treatments in humans. Several pilot studies in this field present promising results, but larger trials are necessary to identify the adverse events and to estimate precisely the place of sex steroids in multiple sclerosis thera‐ peutic strategies.

The objective of this chapter is to summarize the recent advances in the research about the effects of sex steroids in EAE and MS and to create a ground for the development of more powerful treatments in the future.

**Keywords:** EAE, immune modulation, multiple sclerosis, neuroprotection, sex hor‐ mones

#### **1. Introduction**

Gender differences, observed in many aspects of autoimmune diseases, also concern multiple sclerosis (MS) to a high degree. Experimental and clinical data have suggested a role of sex hormones in the pathogenesis of MS and disclose additional therapeutic possibilities.

Initially, empirical observations, such as female prevalence in susceptibility to MS, differences in the clinical presentation between men and women, and the effect of pregnancy on the course of the disease drew attention on the effects of sex hormones in the development of the

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pathological process in MS. Female gender is now regarded as an independent risk factor for the development of the disease, with female:male ratio 3:1, and even higher (3.2:1) in subjects with MS onset before age 20 [1, 2]. Despite this incidence, women do not have poorer prognosis than men, suggesting a biological mechanism underlying these divergences. Pregnancy, the most potent disease‐modifying factor in MS, is a physiological condition characterized with significant hormonal and immunological changes, which raises the idea that sex hormones are implicated in some aspects of the autoimmune process. Many of these observations have been confirmed and elaborated in experimental autoimmune encephalomyelitis (EAE).

The purpose of this chapter is to provide an updated, summarized overview of currently published scientific information about the role of sex hormones in the pathogenesis and clinical course of multiple sclerosis and to outline the perspectives to use this knowledge for control of the disease activity.

An advanced search was conducted, based on the following key words in different combina‐ tions: "multiple sclerosis", "experimental autoimmune encephalomyelitis", "sex hormones", "pregnancy", "cytokines", "estriol", "estradiol", "progesterone", "testosterone", disability", and "MRI". The relevant scientific works (original articles, book chapters, and systematic reviews) published in English, in electronic database (PubMed, MEDLINE, and Medscape) have been retrieved and summarized. The search period was unrestricted. The following inclusion criteria have been determined: (1) subjects, suffering from multiple sclerosis; (2) studies on EAE; (3) assessment of sex hormones and cytokines; (4) brain imaging findings in relation to hormonal concentrations. Case report articles were excluded. A relationship between the concentrations of sex hormones, cytokines, physical disability, and the course of the disease has been searched.
