Hormonal modulation of the immune system — A spotlight on the role of progestogens

Abstract This article reviews the effects of progestogens on the innate and adaptive immunity and its role in the pathogenesis of autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. The interplay between the sex hormones such as progestogens and the immune system is very complex. Multiple factors affect immunomodulatory effects of the progestogens including fluctuations in the endogenous sex hormone levels, stress, use of exogenous hormones (dose, route and the timing of administration), and alterations in the hormonal metabolism. Although immunomodulatory effects of progesterone, especially progesterone's effect on T cells, T cell subsets and their ratios, dose effects, and the use of synthetic progestins have been studied, there are still wide open areas for further explorations of the progestogens' multifaceted impact on the immune system. Better understanding of the intricate immunomodulatory effects of the progestins may pave the path to developing clinically meaningful therapeutic interventions in certain autoimmune diseases.