Progestogens and autoimmunity

Abstract

The immunomodulatory effects of sex hormones are a major factor leading to sexual dimorphism of the human immune system and to the higher susceptibility of females to autoimmune diseases. Data regarding the immunomodulatory effect of estrogens are abundant, but far less is known about progestogens. Recent data indicate that female sex hormones influence immunity and autoimmunity in very different ways: estrogens generally enhance the immune response and increase susceptibility to autoimmunity, while progestogens protect against autoimmunity. Progesterone immunomodulation during pregnancy is of special interest. One of the challenges of pregnancy is to keep the mother safe from infections while keeping the fetus safe from the maternal immune system. Progesterone's immunomodulatory effects may be crucial in balancing these opposing needs. Progesterone enhances Th2 and Treg activity and decreases Th1 and Th17 activity. These actions may underlie the remission of Th1- and Th17- mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis during the high progesterone state of pregnancy. Consequently, progestogens have been reported to be potential treatment for these diseases. Another aspect of the interaction of progestogens with the immune system is progestogen hypersensitivity. This condition is characterized by a hypersensitive reaction to endogenous or exogenous progestogens. The diagnosis is challenging and while effective treatment can sometimes be achieved through suppression of ovulation or progestogen desensitization, in some cases immunosuppressive drugs or even oophorectomy may be required.