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Authors Hagberg KW, Divan HA, Persson R, et al.
Review Date October 2016
Citation BMJ 2016; 354: i4823 (Open Access)
The 5-α reductase inhibitors finasteride (5 mg) and dutasteride (0.5 mg) are used to treat benign prostatic hyperplasia (BPH) and finasteride (at a much lower dose, 1 mg) is also use to treat alopecia. A possible side effect of 5-α reductase inhibitors is sexual dysfunction and some men, particularly those being treated for alopecia, report that sexual dysfunction continues after the withdrawal of treatment. However, there is little robust evidence to quantify the risk of sexual dysfunction associated with finasteride use for alopecia or the underlying pathophysiology of such an effect.
To estimate the risk of erectile dysfunction and non-erectile dysfunction sexual dysfunction (ejaculatory disorder, psychosexual dysfunction, low libido) in men who used 5-α reductase inhibitors to treat benign prostatic hyperplasia or alopecia.
The authors conducted two cohort studies with nested case-control analyses using the UK Clinical Practice Research Datalink, a large longitudinal, population-based electronic medical record database that contains data on about 10 million people (data are collected from GPs). Data from 1992 to 2011 were included. Two populations of men free of risk factors for erectile dysfunction and other sexual dysfunction or its treatment were selected: 1) men aged 40 or more with BPH who received a prescription for a 5-α reductase inhibitor (finasteride or dutasteride) or α-blocker, or both, and 2) men aged 18-59 with alopecia. Men with prostate, genital, or urinary cancer, prostatectomy or orchidectomy, history of erectile dysfunction diagnosis or treatment, other sexual dysfunctions or Peyronie’s disease before cohort entry, or Klinefelter’s syndrome recorded at any time were excluded from both cohorts.
In the BPH group, exposures were classified as 5-α reductase inhibitors only, 5-α reductase inhibitors plus α-blockers, or α-blockers only. In the alopecia study, exposures were finasteride 1 mg or no treatment.
Cases were defined as men with a diagnosis of or treatment (procedure or prescription for a phosphodiesterase type 5 inhibitor) for erectile dysfunction during follow-up. Incidence rates and adjusted incidence rate ratios with 95% confidence intervals were calculated and nested case-control analyses controlling for major confounders with adjusted odds ratios. Men with a diagnosis of a non-erectile dysfunction sexual dysfunction recorded during follow-up were also identified to assess the rates of these outcomes according to the treatments received.
In the cohort of men 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 (IRR) 0.92, 95% confidence interval (CI) 0.85 to 0.99; adjusted odds ratio (AOR) 0.94, 95% CI 0.85 to 1.03) or 5-α reductase inhibitors plus α-blocker (IRR 1.09, 95% CI 0.99 to 1.21, AOR 0.92; 95% CI 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 cohort (n=12,346), the risk of erectile dysfunction was not increased for users of finasteride 1 mg compared with unexposed men with alopecia (IRR 1.03, 95% CI 0.73 to 1.44; AOR 0.95, 95% CI 0.64 to 1.41).
The incidence of non-erectile dysfunction sexual dysfunction was low and considering individual conditions, incidence rates were very low (less than 1 per 1000 person years). Compared with users of α-blockers only, the IRR of non-erectile dysfunction sexual dysfunction adjusted for age, calendar time, and timing of exposure was 1.35 (95% CI 0.95 to 1.91) for users of 5-α reductase inhibitors only and 1.62 (0.79 to 2.72) for users of 5-α reductase inhibitors plus α-blockers in the BPH cohort.
In the alopecia cohort the IRR of sexual dysfunction adjusted for age, calendar time, and timing of exposure was 1.55 (95% CI 0.98 to 2.47) for users of finasteride 1 mg compared with unexposed men.
The results of this study suggest that 5-α reductase inhibitors do not significantly increase the risk of incident erectile dysfunction, regardless of indication for use, in men free of sexual dysfunction and major risk factors at baseline. These findings do not support results from efficacy trials for treatment of BPH where erectile dysfunction risk was elevated with 5-α reductase inhibitors compared to placebo or α-blockers only. However, for alopecia, results of studies assessing sexual dysfunction in men using finasteride have been inconsistent.
This study showed an increased risk of erectile dysfunction with longer duration of BPH, underlining the importance of considering the duration of BPH when assessing sexual dysfunction side-effects.
Points to Note
- In response to patient reports of long-term sexual dysfunction with the use of 5-α reductase inhibitors for the treatment of alopecia, it is important to assess the risk in unbiased studies to support doctors and patients in making informed treatment decisions.
- This study of large cohorts of men in the UK showed no increased risk of diagnosed erectile dysfunction regardless of indication for use of 5-α reductase inhibitors.
- Strengths of the study were the large unbiased cohorts from the UK Datalink database with high accuracy of diagnoses and drug prescription data; exclusion of men with prior erectile dysfunction or risk factors; using GP reports of sexual dysfunction rather than patient report; control of potential confounders.
- Limitations of the study included possible missed prescriptions for PDE5 inhibitors on private prescription; lack of information on the severity of BPH; low number of exposed cases, particularly for non-erectile dysfunction sexual dysfunction in the alopecia population, suggesting caution in interpreting results.
- There are currently other studies looking at the possible pathophysiological basis for how finasteride could affect sexual function; these studies may shed more light on this story.