Progestogens and autoimmunity

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. However, female sex hormones influence immunity and autoimmunity in very different ways: estrogens generally enhance the immune system and increase susceptibility to autoimmunity, while progestogens may be immunosuppressive and protect against autoimmunity. Progesterone immunomodulation during pregnancy is of special interest. One of the challenges of pregnancy is to prevent maternal infections while protecting the fetus from potentially harmful maternal immune responses. Progesterone's immunomodulatory effects may be crucial in balancing these opposing requirements. Progesterone enhances Th2 and Treg activity while decreasing Th1 and Th17 activity. These actions likely contribute to the remission of Th1-mediated and Th17-mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis during the high progesterone state of pregnancy. Accordingly, progestogens may serve as potential treatments for these diseases. Another aspect of the interaction of progestogens with the immune system is progestogen hypersensitivity. This rare condition is characterized by a hypersensitive reaction to endogenous progesterone 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.