A pharmacovigilance study of drug‐reduced male semen quality based on the Food and Drug Administration adverse event reporting system database

Abstract Background Real‐world big data studies on drug‐reduced male semen quality are few and far between, with most studies based on animal trials, small scale retrospective studies, or a limited number of pre‐market clinical trials. Methods This study aimed to identify culprit drugs that reduced male semen quality based on the United States Food and Drug Administration adverse event reporting system. The Medical Dictionary for Regulatory Activities preferred terms and standardized Medical Dictionary for Regulatory Activities queries were used to define reduced male semen quality. Adverse events related to drug‐reduced male semen quality were then analyzed by disproportionality analysis using the United States Food and Drug Administration adverse event reporting system data between 2004 and 2023. Results At the preferred term level, 59 drugs with risk signals were detected to be associated with drug‐reduced male semen quality, with the three most frequently reported second‐level Anatomical Therapeutic Chemical groups being antineoplastic agents ( n = 16, 27.12%), psychoanaleptics ( n = 9, 15.25%), and psycholeptics ( n = 6, 10.17%). At the standardized Medical Dictionary for Regulatory Activities queries level, the five drugs with the greatest number of cases were finasteride (845 cases, IC 025 = 7.72), dutasteride (163 cases, IC 025 = 7.22), tamsulosin (148 cases, IC 025 = 5.99), testosterone (101 cases, IC 025 = 4.08), and valproic acid (54 cases, IC 025 = 2.44). Additionally, clinical information about drug‐reduced male semen quality is absent from the Summary of Product Characteristics of 41 drugs in our study. Conclusions Using the United States Food and Drug Administration adverse event reporting system database, we offer a list of drugs with risk signals for reducing male semen quality. In the future, there is still a need for more studies on drugs whose effects on male semen quality are not fully understood.