Do immunomodulatory drugs impact female reproductive health? 4293

Abstract Description Histamine type 2 receptor (H2R) blockers are commonly used as gastric acid suppressants. However, studies leading to their approval were conducted with a disproportionately high male-to-female ratio, resulting in a lack of understanding regarding the gynecological impacts of these compounds. Strikingly, reproductive safety was not further explored, largely due to the “absence of estrogenic activity.” The impact of H2R blockade on the immune system was described long ago, but it has only recently been considered from an immunomodulatory perspective. H2R-blockers affect both T- and B-cell function, as well as the production of cytokines involved in the response to noxious agents. While H2R expression throughout the female and murine uterus has been known, its function outside of pregnancy is not understood. Electronic Health Record (EHR) data analysis revealed a significant association between the use of cimetidine and diverse gynecological pathologies. Surprisingly, histamine-driven signals seem to play a crucial role in female reproductive tract’s (FRT) pathology. Our group found that BL/6 mice treated with H2R blockers developed soft tissue edema, uterine and ovarian cysts, and endometrial hyperplasia, among other striking FRT pathologies. The underrepresentation of women in drug trials raises concerns about the gynecological safety of H2R blockers. This highlights an urgent need to investigate the effects of these commonly used drugs on the female reproductive system. Topic Categories Immune Mechanisms of Human Disease (HUM)