Progesterone-based compounds affect immune responses and susceptibility to infections at diverse mucosal sites

Abstract

Over 100 million women worldwide are currently on progesterone-based contraceptives to improve their health outcomes through reduced maternal mortality and family planning. In addition to their role in reproduction, progesterone-based compounds modulate immune responses throughout the body, particularly at mucosal sites. By binding to receptors located in immune cells, including natural killer cells, macrophages, dendritic cells, and T cells, as well in non-immune cells, such as epithelial and endothelial cells, progesterone-based compounds alter cellular signaling and activity to affect the outcome of infections at diverse mucosal sites, including the genital, gastrointestinal, and respiratory tracts. As the use of progesterone-based compounds, in the form of contraceptives and hormone-based therapies, continue to increase worldwide, greater consideration should be given to how the immunomodulatory effects these compounds alter the outcome of diseases at mucosal sites beyond the reproductive tract, which has profound implications for women's health.

Vaginal progesterone is associated with decreased group B streptococcus colonisation at term: a retrospective cohort study

“…Progesterone receptors are present on immune cells, suggesting that progesterone may have a direct effect on the immune response to disease. Indeed, in vitro studies suggest that progesterone may inhibit macrophage and dendritic cell activation, inhibit pro‐inflammatory cytokine and increase anti‐inflammatory cytokine production, affect the activity and distribution of T‐cells, encouraging a Th2 rather than Th1 response, and inhibit B‐cell development …”

“…Clinical studies do reflect these molecular interactions and suggest that progestogens change the host susceptibility to infection. Progestogens have been shown to reduce the incidence of candidal vaginitis and bacterial vaginosis . Additionally, progestogens have been shown to have antibacterial functions, can inhibit the growth the Neisseria gonorrhea , and can alter the gastric mucosal response to impair the viability of Helicobacter pylori .…”

“…Indeed, in vitro studies suggest that progesterone may inhibit macrophage and dendritic cell activation, inhibit pro-inflammatory cytokine and increase anti-inflammatory cytokine production, affect the activity and distribution of T-cells, encouraging a Th2 rather than Th1 response, and inhibit B-cell development. [25][26][27][28][29]31 Clinical studies do reflect these molecular interactions and suggest that progestogens change the host susceptibility to infection. Progestogens have been shown to reduce the incidence of candidal vaginitis and bacterial vaginosis.…”

“…The literature on whether progestogens have an effect on the vaginal microbiome is conflicting . Progesterone has known antibacterial, immunomodulatory, and anti‐inflammatory properties, with demonstrated effects on dendritic cells, macrophages, T‐cells, B‐cells, and cytokine release . Animal models have demonstrated that intravaginal progesterone has local anti‐inflammatory effects at the maternal–fetal interface and the cervix .…”

“…[17][18][19][20][21] Progesterone has known antibacterial, immunomodulatory, and anti-inflammatory properties, [22][23][24] with demonstrated effects on dendritic cells, macrophages, T-cells, B-cells, and cytokine release. [25][26][27][28][29][30][31] Animal models have demonstrated that intravaginal progesterone has local anti-inflammatory effects at the maternalfetal interface and the cervix. 32 17-OHP-C was not found to have these properties.…”