Effect of 5α-Reductase Inhibitors on Sexual Function: A Meta-Analysis and Systematic Review of Randomized Controlled Trials

Abstract

Introduction 5α-Reductase inhibitors (5ARIs) are widely used for the treatment of benign prostatic hyperplasia (BPH) and androgenetic alopecia (AGA). Aim To review all the available data on the effect of 5ARIs on sexual function and assess whether 5ARIs increase the risk of sexual dysfunction. Methods A systematic search of the literature was conducted using the Medline, Embase, and Cochrane databases. The search was limited to articles published in English and up to October 2015. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. Data were analyzed using Stata 12.0. A fixed- or a random-effects model was used to calculate the overall combined risk estimates. Publication bias was assessed using Begg and Egger tests. Main Outcome Measures Sexual dysfunction, erectile dysfunction, and decreased libido. Results After screening 493 articles, 17 randomized controlled trials with 17,494 patients were included. Nine studies evaluated the efficacy of 5ARIs in men with BPH. The other eight reported using 5ARIs in the treatment of men with AGA. The mean age of participants was 60.10 years across all studies. We included 10 trials (6,779 patients) on the efficacy and safety of finasteride, 4 trials (6,222 patients) on the safety and tolerability of dutasteride, and 3 trials (4,493 patients) using finasteride and dutasteride for AGA. The pooled relative risks for sexual dysfunction were 2.56 (95% CI = 1.48–4.42) in men with BPH and 1.21 (95% CI = 0.85–1.72) in men with AGA; those for erectile dysfunction were 1.55 (95% CI = 1.14–2.12) in men with BPH and 0.66 (95% CI = 0.20–2.25) in men with AGA; and those for decreased libido were 1.69 (95% CI = 1.03–2.79) in men with BPH and 1.16 (95% CI = 0.50–2.72) in men with AGA. Estimates of the total effects were generally consistent with the sensitivity analysis. No evidence of publication bias was observed. Conclusion Evidence from the randomized controlled trials suggested that 5ARIs were associated with increased adverse effects on sexual function in men with BPH compared with placebo. However, the association was not statistically significant in men with AGA. Well-designed randomized controlled trials are indicated to study further the mechanism and effects of 5ARIs on sexual function.

‘Post-finasteride syndrome’: what to tell our female patients?

“…Purported mechanisms for these effects include the decreased production of neurosteroids, which may regulate sexual desire and function, and impaired testosterone metabolism, leading to relative oestrogen excess . Large randomized controlled trials of men on 5‐alpha‐reductase inhibitors for benign prostatic hypertrophy have shown increased sexual dysfunction compared with placebo; however, similar association with male pattern hair loss was not statistically significant . Sexual side‐effects have been reported by 43·6% of men informed about these potential effects vs. 15·3% in the uninformed .…”

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

“…High‐quality studies were found to report persistent sexual side‐effects more frequently in placebo groups versus treated individuals suggesting that sexual dysfunction is not a direct result of therapy . A literature review of studies prescribing 5αRIs for androgenetic AGA versus BPH revealed a significant association between sexual dysfunction adverse events in BPH patients but not among AGA patients . Some suggest age may be a confounding factor, as sexual dysfunction increases with age, and BPH generally affects older men and necessitates a higher dose of 5αRI .…”

Androgen receptor (AR) gene (CAG)n and (GGN)n length polymorphisms and symptoms in young males with long-lasting adverse effects after finasteride use against androgenic alopecia

“…5,10,12 A meta-analysis on the effects of 5a-reductase inhibitors found a significant pooled relative risk for sexual dysfunction in men with benign prostatic hyperplasia (2.56, 95% CI ¼ 1.48e4.42) but no significant increased risk in men with AGA (1.21, 95% CI ¼ 0.85e1.72). 13 Recently, a clinical study described the main symptoms of subjects with PFS, including loss of penis sensitivity, decreased ejaculatory force, low penile temperature, smaller ejaculatory volume, anhedonia, lack of mental concentration, and loss of muscle tone or mass. 4 In particular, an immunohistochemical study found increased levels of the androgen receptor (AR) in epithelial and stromal cells from the foreskin of eight men with PFS compared with healthy men.…”