I. Introduction

THE remarkable female predominance of such diverse autoimmune diseases as systemic lupus erythematosus (SLE), Hashimoto's thyroiditis, rheumatoid arthritis, and primary biliary cirrhosis has suggested to many clinicians that hormonal differences between the sexes must confer some protective effect on males or enhance the susceptibility of females to these diseases. This review will examine the evidence in support of such an hypothesis. We will examine the effects of gonadal steroids on the function of the normal immune system as well as their impact on autoimmune processes. We will explore current knowledge of the cellular and molecular mechanisms by which gonadal steroids might modulate both normal and disordered function of the immune system.

II. Physiology and Pathophysiology of Gonadal Steroid Effects on Immunity

A. Normal immune responses are sexually dimorphic

A significant body of data establishes that a number of aspects of immune responsiveness normally differ between males and females.