Serenoa repens monotherapy for benign prostatic hyperplasia (BPH): an updated Cochrane systematic review

What's known on the subject? and What does the study add? For the past 30 years Serenoa repens has become a widely used phytotherapy in the USA and in Europe, mostly because of positive comparisons to α-blockers and 5α-reductase inhibitors. During the last 4 years we have seen two very high quality trials comparing Serenoa repens to placebo and up to 72 weeks' duration. These trials found Serenoa repens no better than placebo, even (in one trial) at escalating doses.

• To estimate the effectiveness and harms of Serenoa repens monotherapy in the treatment of lower urinary tract symptoms (LUTS) consistent with benign prostatic hyperplasia (BPH).

• We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and other sources through to January 2012 to identify randomised trials. • Trials were eligible if they randomised men with symptomatic BPH to receive Serenoa repens extract monotherapy for at least 4 weeks in comparison with placebo, and assessed clinical outcomes and urodynamic measurements. • Our primary outcome was improvement in LUTS, based on change in urological symptom-scale scores.

• In all, 17 randomised controlled trials (N= 2008) assessing Serenoa repens monotherapy (typically 320 mg/day) vs placebo met inclusion criteria, although only five reported American Urological Association Symptom Index (AUASI) or International Prostate Symptom Scores (IPSS). Trial lengths ranged from 4 to 72 weeks. The mean age of all enrolees was 64.3 years and most participants were of White race. The mean baseline total score was 14 points, indicating moderately severe symptoms. In all, 16 trials were double blinded and adequate treatment allocation concealment was reported in six trials. • In a meta-analysis of three high quality long-to-moderate term trials (n= 661), Serenoa repens therapy was no better than placebo in reducing LUTS based on the AUASI/IPSS (weighted mean difference [WMD]-0.16 points, 95% confidence interval [CI]-1.45 to 1.14) or maximum urinary flow rate (Q(max) ; WMD 0.40 mL/s, 95% CI -0.30 to 1.09). Based on mostly short-term studies, Q(max) measured at study endpoint were also not significantly different between treatment groups (WMD 1.15 mL/s, 95% CI -0.23 to 2.53) with evidence of substantial heterogeneity (I(2) 58%). • One long-term dose escalation trial (72 weeks) found double and triple doses of Serenoa repens extract did not improve AUASI compared with placebo and the proportions of clinical responders (≥ 3 point decrease in the AUASI) were nearly identical (43% vs 44% for Serenoa repens and placebo, respectively) with a corresponding risk ratio of 0.96 (95% CI 0.76-1.22). • Long-term, Serenoa repens therapy was no better than placebo in improving nocturia in one high-quality study (P= 0.19). Pooled analysis of nine short-term Permixon® trials showed a reduction in the frequency of nocturia (WMD -0.79 times/night, 95% CI-1.28 to -0.29), although there was evidence of heterogeneity (I(2) 76%) • Adverse events of Serenoa repens extracts were few and mild, and incidences were not statistically significantly different vs placebo. Study withdrawals occurred in ≈ 10% and did not differ between Serenoa repens and placebo.

• Serenoa repens therapy does not improve LUTS or Q(max ) compared with placebo in men with BPH, even at double and triple the usual dose. • Adverse events were generally mild and comparable to placebo.