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

Abstract

ImportanceCase reports describe persistent erectile dysfunction (PED) associated with exposure to 5α-reductase inhibitors (5α-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 5α-RI exposure and that sexual adverse effects of 5α-RIs resolve in men who discontinue exposure.ObjectiveOur chief objective was to assess whether longer duration of 5α-RI exposure increases risk of PED, independent of age and other known risk factors. Men with shorter 5α-RI exposure served as a comparison control group for those with longer exposure.DesignWe used a single-group study design and classification tree analysis (CTA) to model PED (lasting ≥90 days after stopping 5α-RI). Covariates included subject attributes, diseases, and drug exposures associated with sexual dysfunction.SettingOur data source was the electronic medical record data repository for Northwestern Medicine.SubjectsThe 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 ≤1.25 mg/day.Main outcome and measuresOur main outcome measure was diagnosis of PED beginning after first 5α-RI exposure, continuing for at least 90 days after stopping 5α-RI, and with contemporaneous treatment with a phosphodiesterase-5 inhibitor (PDE5I). 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).ResultsAmong men with 5α-RI exposure, 167 of 11,909 (1.4%) developed PED (persistence median 1,348 days after stopping 5α-RI, interquartile range (IQR) 631.5–2320.5 days); the multivariable model predicting PED had four variables: prostate disease, duration of 5α-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 5α-RI exposure had 4.8-fold higher risk of PED than men with shorter exposure (NNH 59.8, all p < 0.002). Among men 16–42 years old and exposed to finasteride ≤1.25 mg/day, 34 of 4,284 (0.8%) developed PED (persistence median 1,534 days, IQR 651–2,351 days); the multivariable model predicting PED had one variable: duration of 5α-RI exposure. Of 103 young men with new ED, 34 (33%) had new PED. Young men with >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 relevanceRisk of PED was higher in men with longer exposure to 5α-RIs. Among young men, longer exposure to finasteride posed a greater risk of PED than all other assessed risk factors.

A randomized, double‐blind controlled study of the efficacy and safety of topical solution of 0.25% finasteride admixed with 3% minoxidil vs. 3% minoxidil solution in the treatment of male androgenetic alopecia

“…Predisposition to the disease depends mainly on genetics, and the pattern is most likely polygenic inheritance. [22][23][24] A meta-analysis highlights that 34 clinical trials of finasteride for AGA had no adequate safety reporting. An excess of DHT conversion in the hair follicles is suspected to cause hair miniaturization in male patients with AGA.…”

“…[4][5][6][7] However, persistent sexual dysfunction continues to be mentioned in case reports and uncontrolled studies. [22][23][24] A meta-analysis highlights that 34 clinical trials of finasteride for AGA had no adequate safety reporting. 25 It is suggesting that adverse effects of finasteride use are possibly underdetected.…”

A prospective randomised placebo‐controlled study of the impact of dutasteride/tamsulosin combination therapy on sexual function domains in sexually active men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH)

“…Although supported by guideline recommendations , patient preference , and clinical studies findings indicating efficacy , clinicians are reluctant to initiate 5ARI therapy due to the potential for sexual dysfunction . In nearly all studies conducted in this area to date, the assessment of sexual function has been restricted to the overall incidence of sexually‐related adverse events (AEs) reported spontaneously as part of regular clinical trial AE reporting .…”

Post-finasteride syndrome

“…Post-finasteride syndrome is an ill defined and controversial syndrome associated with a constellation of sexual, physical, and psychological symptoms that develop during or after finasteride exposure and persist after discontinuation (box 1). 35 The incidence of post-finasteride syndrome is unknown, as are the biological mechanisms, but we know that 5α-reductase inhibitors reduce synthesis of brain neurosteroids, which affect mood, cognition, and libido 36…”