Risk of erectile dysfunction associated with use of 5-α reductase inhibitors for benign prostatic hyperplasia or alopecia: population based studies using the Clinical Practice Research Datalink

Abstract

ObjeCtiveTo estimate the risk of erectile dysfunction in men who used 5-α reductase inhibitors to treat benign prostatic hyperplasia or alopecia. DesignCohort studies with nested case-control analyses. POPulatiOnTwo populations of men free of risk factors for erectile dysfunction and other sexual dysfunction or its treatment: men aged 40 or more with benign prostatic hyperplasia who received a prescription for a 5-α reductase inhibitor (finasteride or dutasteride) or α blocker, or both, and men aged 18-59 with alopecia. exPOsuresIn the benign prostatic hyperplasia study, exposures were classified as 5-α reductase inhibitors only, 5-α reductase inhibitors+α blockers, or α blockers only. In the alopecia study, exposures were finasteride 1 mg or no treatment. Main OutCOMe MeasuresCases were men with a diagnosis of erectile dysfunction or treatment (procedure or prescription for a phosphodiesterase type 5 inhibitor) during follow-up. We calculated incidence rates and adjusted incidence rate ratios with 95% confidence intervals. We also conducted nested case-control analyses to control for major confounders, and calculated adjusted odds ratios with 95% confidence intervals. resultsIn the population with benign prostatic hyperplasia (n=71 849), the risk of erectile dysfunction was not increased with use of 5-α reductase inhibitors only (incidence rate ratio 0.92, 95% confidence interval 0.85 to 0.99; odds ratio 0.94, 95% confidence interval 0.85 to 1.03) or 5-α reductase inhibitors+α blocker (1.09, 0.99 to 1.21, 0.92; 0.80 to 1.06) compared with α blockers only, and remained null regardless of number of prescriptions or timing of use. The risk of erectile dysfunction increased with longer duration of benign prostatic hyperplasia, regardless of exposure. For the alopecia population (n=12 346), the risk of erectile dysfunction was not increased for users of finasteride 1 mg compared with unexposed men with alopecia (1.03, 0.73 to 1.44; 0.95, 0.64 to 1.41).COnClusiOn 5-α reductase inhibitors do not seem to significantly increase the risk of incident erectile dysfunction, regardless of indication for use. Risk of erectile dysfunction increased with longer duration of benign prostatic hyperplasia.

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

“…A meta-analysis of clinical trials in men with prostatic hyperplasia found that the risk of ED was significantly increased with combined 5α-RI plus α 2 adrenergic receptor blocker compared to α 2 adrenergic receptor blocker alone (Favilla et al, 2016). However, an observational study found that the risk of ED was not increased with combined 5α-RI plus α 2 adrenergic receptor blocker compared to α 2 adrenergic receptor blocker alone (Hagberg et al, 2016). A case-control study found that sexual and erectile function of men exposed to finasteride 1 mg daily did not differ from controls (Tosti, Piraccini & Soli, 2001), and an observational study found that sexual function in men did not decline over the first 4–6 months of exposure to finasteride 1 mg (Tosti et al, 2004).…”

Risk of Incident Antidepressant‐Treated Depression Associated with Use of 5α‐Reductase Inhibitors Compared with Use of α‐Blockers in Men with Benign Prostatic Hyperplasia: A Population‐Based Study Using the Clinical Practice Research Datalink

“…To identify men with first‐time (incident) antidepressant‐treated depression after treatment with a study drug, we excluded men with a diagnosis of depression or suicidal behaviors (ideation or attempts), or men who received prescriptions for antidepressant medications prior to cohort entry. These methods were described in more detail in a prior publication …”

Assessing dutasteride‐associated sexual dysfunction using the U.S. Food and Drug Administration Adverse Event Reporting System

“…These results add to the possibility of a connection between sexual dysfunction and 5αRI use (for any age) although alternative explanations such as a nocebo effect and duration of BPH are contributors. It has been suggested that in trials where dutasteride is indicated for BPH, it is the duration of disease that increases the risk for sexual dysfunction versus finasteride or dutasteride used to treat the condition . There is also evidence that presenting the possibility of sexual dysfunction with 5αRI use to patients increases incidences even with placebo use, establishing the presence of a nocebo or psychologically induced detrimental effect .…”