Is the Safety of Finasteride Correlated With Its Route of Administration: Topical Versus Oral? A Pharmacovigilance Study With Data From the United States Food and Drug Administration Adverse Event Reporting System.

Background: The United States Food and Drug Administration (FDA) approved oral finasteride for androgenetic alopecia. In 2022, approximately 2.6 million U.S. men used it for hair loss and prostate conditions. Post-finasteride syndrome (PFS), proposed in 2012, involves persistent sexual and neuropsychiatric adverse events (AEs) after cessation. These AEs are controversial and often lack assessment of contributing risk factors. We analyzed FDA Adverse Event Reporting System (FAERS) data to explore finasteride's administration route and PFS-like AEs.

Methods: Using the information component (IC) method for disproportionality analyses, we assessed signals for 13 PFS-related AEs with topical and oral finasteride and dutasteride across two periods: 2006-2011 (pre-PFS reporting) and 2019-2024 (post-PFS reporting). These periods reflect times before and after formal PFS reporting in 2012. Eight analyses per AE were conducted based on agent, route, and era.

Results: Fewer signals for PFS-like AEs were detected with topical finasteride compared to oral finasteride in both eras. No signals were found for topical dutasteride, possibly because its use is very limited. Many reported AEs, such as erectile dysfunction and depression, may be influenced by age, stress, or comorbidities.

Conclusions: Signals for PFS-like AEs were detected with topical finasteride, but were less frequent than with oral finasteride. The high prevalence of these AEs in the general population and the influence of confounding factors, such as psychological stress or nocebo effects, combined with the lack of genotyping, hormonal assessments, or family history data in most reports, suggest caution in attributing causality to finasteride. Topical finasteride may pose a lower risk, but robust evidence is needed to clarify its safety profile.