Abstract Text: Cimetidine is a histamine-2 (H-2) receptor blocker that was FDA approved in 1979 through clinical trials that were predominantly male. While originally approved for short-term prescription use, cimetidine has been available over the counter since 1995. Once sold solely under the brand name Tagamet, cimetidine remains available globally in generic formulations. Daily consumption of this antihistamine for periods of 4 months or longer in mice leads to significant uterine abnormalities by gross pathology and histopathology including severe disfigurement, swelling, and cysts. Female post-menopausal mice also showed endometrial hyperplasia. Furthermore, combination of exposure to this antihistamine concurrently with a bacterial infection that colonizes the uterus leads to hemorrhaging and/or pyometra in the female mouse. We are actively investigating common antihistamines on the market of both H-1 and H-2 receptor blocker types to evaluate their impact on the murine female reproductive tract. We are also investigating epidemiological associations between the use of these antihistamines and gynecological diseases. These data will help us better understand the role of histamine in the female reproductive tract. Furthermore, this study highlights the importance of more inclusive clinical trials and perhaps the need to revisit current FDA approved drugs that were not sufficiently tested in females.
