Safety profile of progesterone: Insights from an FDA Adverse Event Reporting System (FAERS)–based pharmacovigilance study

ObjectiveThis study aimed to evaluate the safety profile of progesterone by analyzing adverse event data from the Food and Drug Administration Adverse Event Reporting System (FAERS) between 2004 and 2024.Materials and methodsThis retrospective, observational pharmacovigilance study was based on data from the FAERS database. A total of 1827 adverse event reports associated with progesterone were retrieved. Disproportionality analysis methods, including the reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker, were used to evaluate the frequency, signal strength, and time-to-onset of adverse events.ResultsAmong 24,589,239 adverse event reports in the reporting system, 1827 were associated with progesterone, covering 22 system organ classes and 152 preferred terms. The most frequently reported preferred terms were maternal exposure during pregnancy (151 cases), spontaneous abortion (144 cases), and abnormal product odor (114 cases). The top three preferred terms showing the strongest signals were decidual cast (reporting odds ratio: 2825.23), chondrodermatitis nodularis chronica helicis (reporting odds ratio: 3897.61), and autoimmune dermatitis (reporting odds ratio: 1519.29). Most adverse events occurred within 30 to 180 days after exposure. Newly identified preferred terms associated with progesterone included acute eosinophilic pneumonia, meningioma, and autoimmune dermatitis.ConclusionsThis study identified notable safety concerns associated with progesterone use and detected several rare adverse events. These findings underscore the need for continued monitoring, updated prescribing guidelines, and further investigation into progesterone formulations and adverse event mechanisms.