Sex hormones, immune responses, and autoimmune diseases. Mechanisms of sex hormone action

Am J Pathol. 1985 Dec;121(3):531-51.


Immune reactivity is greater in females than in males. In both experimental animals and in man there is a greater preponderance of autoimmune diseases in females, compared with males. Studies in many experimental models have established that the underlying basis for this sex-related susceptibility is the marked effects of sex hormones. Sex hormones influence the onset and severity of immune-mediated pathologic conditions by modulating lymphocytes at all stages of life, prenatal, prepubertal, and postpubertal. However, despite extensive studies, the mechanisms of sex hormone action are not precisely understood. Earlier evidence suggested that the sex hormones acted via the thymus gland. In recent years it has become apparent that sex hormones can also influence the immune system by acting on several nonclassic target sites such as the immune system itself (nonthymic lymphoid organs), the central nervous system, the macrophage-macrocyte system, and the skeletal system. Immunoregulatory T cells appear to be most sensitive to sex hormone action among lymphoid cells. Several mechanisms of action of sex hormones are discussed in this review. The possibility of using sex hormone modulation of immune responses for the treatment of autoimmune disorders is a promising area for future investigation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Antibody-Producing Cells / immunology
  • Autoimmune Diseases / physiopathology*
  • B-Lymphocytes / immunology
  • Castration
  • Estrogens / pharmacology
  • Estrogens / physiology
  • Female
  • Gonadal Steroid Hormones / pharmacology
  • Gonadal Steroid Hormones / physiology*
  • Humans
  • Immunization
  • Killer Cells, Natural / immunology
  • Lupus Erythematosus, Systemic / physiopathology
  • Lymphatic System / immunology
  • Lymphatic System / physiology
  • Male
  • Mice
  • Rats
  • Receptors, Androgen*
  • Receptors, Estrogen / physiology
  • Receptors, Steroid / physiology
  • Sex Factors
  • T-Lymphocytes / immunology
  • Testosterone / pharmacology
  • Testosterone / physiology
  • Thyroiditis / etiology
  • Thyroiditis / immunology
  • Thyroiditis / physiopathology


  • Estrogens
  • Gonadal Steroid Hormones
  • Receptors, Androgen
  • Receptors, Estrogen
  • Receptors, Steroid
  • Testosterone