Background
Benign prostatic hyperplasia (BPH) refers to non‐malignant enlargement of the prostate gland that may cause bothersome lower urinary tract symptoms (LUTS). Alpha‐blockers (ABs) and 5‐alpha reductase inhibitors (5‐ARIs) are the mainstay of medical treatment. Recently, phosphodiesterase inhibitors (PDEIs) that so far have been used mainly to treat erectile dysfunction were introduced to treat male LUTS.
Objectives
To assess the effects of PDEIs compared to placebo and other standard of care drugs (ABs and 5‐ARIs) in men with LUTS consistent with BPH.
Search methods
We conducted a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Web of Science, and clinical trials registries of the World Health Organization (WHO) and the National Institutes of Health (NIH) (updated 2 August 2018). We performed citation tracking and handsearching of abstracts and conference proceedings. We also contacted study authors to ask for additional information.
Selection criteria
We considered for inclusion in this systematic review randomised controlled trials (RCTs) comparing PDEIs versus placebo, ABs, or 5‐ARIs for at least four weeks in men with BPH‐LUTS.
Data collection and analysis
Three review authors independently screened the literature and extracted data. Primary outcomes were effects on urinary symptoms as assessed by the International Prostate Symptom Score (IPSS‐total; score ranging from 0 to 35, with higher values reflecting more symptoms), urinary bother as assessed by the Benign Prostatic Hyperplasia Impact Index (BPHII; score ranging from 0 to 13, with higher values reflecting more bother), and adverse events (AEs). We used GRADE to rate the quality of evidence. We considered short‐term (up to 12 weeks) and long‐term (12 weeks or longer) results separately.
Main results
We included a total of 16 randomised trials in this review. The results for primary outcomes are as follows.
PDEI versus placebo: PDEIs may result in a small improvement in IPSS‐total score (mean difference (MD) 1.89 lower, 95% confidence interval (CI) 2.27 lower to 1.50 lower; n = 4293; low‐quality evidence) compared to placebo, and may reduce the BPHII score slightly (MD 0.52 lower, 95% CI 0.71 lower to 0.33 lower; n = 3646; low‐quality evidence). Rates of AEs may be increased (risk ratio (RR) 1.42, 95% CI 1.21 to 1.67; n = 4386; low‐quality evidence). This corresponds to 95 more AEs per 1000 participants (95% CI 47 more to 151 more per 1000). Study results were limited to a treatment duration of six to 12 weeks.
PDEI versus AB: PDEIs and ABs probably provide similar improvement in IPSS‐total score (MD 0.22 higher, 95% CI 0.49 lower to 0.93 higher; n = 933; moderate‐quality evidence) and may have a similar effect on BPHII score (MD 0.03 higher, 95% CI 1.10 lower to 1.16 higher; n = 550; low‐quality evidence) and AEs (RR 1.35, 95% CI 0.80 to 2.30; n = 936; low‐quality evidence). This corresponds to 71 more AEs per 1000 participants (95% CI 41 fewer to 264 more per 1000). Study results were limited to a treatment duration of six to 12 weeks.
PDEI and AB versus AB alone: the combination of PDEI and AB may provide a small improvement in IPSS‐total score (MD 2.56 lower, 95% CI 3.92 lower to 1.19 lower; n = 193; low‐quality evidence) compared to AB alone. We found no evidence for BPHII scores. AEs may be increased (RR 2.81, 95% CI 1.53 to 5.17; n = 194; moderate‐quality evidence). This corresponds to 235 more AEs per 1000 participants (95% CI 69 more to 542 more per 1000). Study results were limited to treatment duration of four to 12 weeks.
PDEI and AB versus PDEI alone: the combination of PDEI and AB may provide a small improvement in IPSS‐total (MD 2.4 lower, 95% CI 6.47 lower to 1.67 higher; n = 40; low‐quality evidence) compared to PDEI alone. We found no data on BPHII or AEs. Study results were limited to a treatment duration of four weeks.
PDEI and 5‐ARI versus 5‐ARI alone: in the short term (up to 12 weeks), the combination of PDEI and 5‐ARI probably results in a small improvement in IPSS‐total score (MD 1.40 lower, 95% CI 2.24 lower to 0.56 lower; n = 695; moderate‐quality evidence) compared to 5‐ARI alone. We found no evidence on BPHII scores or AEs. In the long term (13 to 26 weeks), the combination of PDEI and 5‐ARI likely results in a small reduction in IPSS‐total score (MD 1.00 less, 95% CI 1.83 lower to 0.17 lower; n = 695; moderate‐quality evidence). We found no evidence about effects on BPHII scores. There may be no difference in rates of AEs (RR 1.07, 95% CI 0.84 to 1.36; n = 695; low‐quality evidence). This corresponds to 19 more AEs per 1000 participants (95% CI 43 fewer to 98 more per 1000).
We found no trials comparing other combinations of treatments or comparing different PDEI agents.
