Persistent erectile dysfunction in men exposed to the 5[alpha]-reductase inhibitors, finasteride, or dutasteride

• Published in: PeerJ (San Francisco, CA) Vol. 5; p. e3020
• Main Authors: Kiguradze, Tina, Temps, William H, Yarnold, Paul R, Cashy, John, Brannigan, Robert E, Nardone, Beatrice, Micali, Giuseppe, West, Dennis Paul, Belknap, Steven M
• Format: Journal Article
• Language: English
• Published: PeerJ. Ltd 09.03.2017
• Subjects: Causes of; Dutasteride; Finasteride; Health aspects; Impotence
• ISSN: 2167-8359; 2167-8359
• DOI: 10.7717/peerj.3020

Importance Case reports describe persistent erectile dysfunction (PED) associated with exposure to 5[alpha]-reductase inhibitors (5[alpha]-RIs). Clinical trial reports and the manufacturers' full prescribing information (FPI) for finasteride and dutasteride state that risk of sexual adverse effects is not increased by longer duration of 5[alpha]-RI exposure and that sexual adverse effects of 5[alpha]-RIs resolve in men who discontinue exposure. Objective Our chief objective was to assess whether longer duration of 5[alpha]-RI exposure increases risk of PED, independent of age and other known risk factors. Men with shorter 5[alpha]-RI exposure served as a comparison control group for those with longer exposure. Design We used a single-group study design and classification tree analysis (CTA) to model PED (lasting [greater than or equal to]90 days after stopping 5[alpha]-RI). Covariates included subject attributes, diseases, and drug exposures associated with sexual dysfunction. Setting Our data source was the electronic medical record data repository for Northwestern Medicine. Subjects The analysis cohorts comprised all men exposed to finasteride or dutasteride or combination products containing one of these drugs, and the subgroup of men 16-42 years old and exposed to finasteride [less than or equal to]1.25 mg/day. Main outcome and measures Our main outcome measure was diagnosis of PED beginning after first 5[alpha]-RI exposure, continuing for at least 90 days after stopping 5[alpha]-RI, and with contemporaneous treatment with a phosphodiesterase-5 inhibitor (PDE.sub.5 I). Other outcome measures were erectile dysfunction (ED) and low libido. PED was determined by manual review of medical narratives for all subjects with ED. Risk of an adverse effect was expressed as number needed to harm (NNH). Results Among men with 5[alpha]-RI exposure, 167 of 11,909 (1.4%) developed PED (persistence median 1,348 days after stopping 5[alpha]-RI, interquartile range (IQR) 631.5-2320.5 days); the multivariable model predicting PED had four variables: prostate disease, duration of 5[alpha]-RI exposure, age, and nonsteroidal anti-inflammatory drug (NSAID) use. Of 530 men with new ED, 167 (31.5%) had new PED. Men without prostate disease who combined NSAID use with >208.5 days of 5[alpha]-RI exposure had 4.8-fold higher risk of PED than men with shorter exposure (NNH 59.8, all p 205 days of finasteride exposure had 4.9-fold higher risk of PED (NNH 108.2, p < 0.004) than men with shorter exposure. Conclusion and relevance Risk of PED was higher in men with longer exposure to 5[alpha]-RIs. Among young men, longer exposure to finasteride posed a greater risk of PED than all other assessed risk factors.