Drug-associated hyperprolactinemia: A comprehensive disproportionality analysis based on the FAERS database

Hyperprolactinemia (HPRL) is a clinically significant adverse event that requires careful monitoring. This study aims to identify the medications associated with HPRL using data from the FDA Adverse Event Reporting System (FAERS) between 2004Q1 and 2024Q1. Disproportionality analysis was performed to identify potential drug signals. Sensitivity analysis was conducted to assess the stability and strength of HPRL signals associated with these medications, as well as to examine signal differences by age and gender through stratification. Time-to-onset (TTO) analysis was performed to investigate the factors affecting the onset of HPRL. Disproportionality analyses identified 39 drugs related to HPRL across six main anatomical systems, with the majority (N = 29) affecting the nervous system. Notably, most of these medications belong to psychotropic categories, including atypical antipsychotics (AAPs, N = 13), typical antipsychotics (TAPs, N = 5) and selective serotonin reuptake inhibitors (SSRIs, N = 5). Sensitivity analysis indicated that most signals remained robust, with risperidone exhibiting the strongest signal for HPRL, followed by amisulpride, paliperidone, fluphenazine, and thioridazine. Stratified analysis showed that females had stronger signals for HPRL. Compared to individuals aged 18-44, those aged ≥45 exhibited weaker signals, while the signals in minors varied by drug. TTO analysis revealed that AAP-related HPRL manifested earlier in females, with earlier onset observed in minors using AAPs or SSRIs. In conclusion, we identified and ranked drugs associated with HPRL, primarily psychotropic medications, and observed variations in signal strength and onset time across gender and age. These findings emphasize the importance of individualized HPRL screening based on specific medications, gender, and age.