PMID- 30281615 OWN - NLM STAT- MEDLINE DCOM- 20190306 LR - 20190402 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 13 IP - 10 DP - 2018 TI - Efficacy and safety of 5 alpha-reductase inhibitor monotherapy in patients with benign prostatic hyperplasia: A meta-analysis. PG - e0203479 LID - 10.1371/journal.pone.0203479 [doi] LID - e0203479 AB - BACKGROUND: Although combination therapy with 5 alpha-reductase inhibitor (5ARI) and alpha-blocker is one of the standard interventions in symptomatic benign prostatic hyperplasia (BPH), 5ARI monotherapy is seldom the focus of attention. Adverse events associated with 5ARI include depression and suicidal attempts in addition to persistent erectile dysfunction. The aim of this study is to update our knowledge of clinical efficacy and incidence of adverse events associated with 5ARI treatment in symptomatic BPH. METHODS AND FINDINGS: A meta-analysis of randomized controlled clinical trials (RCTs) from 1966 until March, 2017 was performed using database from PubMed, Cochrane Collaboration and Embase. A total of 23395 patients were included in this study and the inclusion criteria were: RCTs with 5ARI and placebo in symptomatic BPH patients. Parameters included prostate specific antigen (PSA), prostate volume (PV), International Prostate Symptom Score (IPPS), post-void residual urine (PVR), voiding symptoms of IPSS (voiding IPSS), maximum urinary flow rate (Qmax), and adverse events (AEs). A meta-analysis with meta-regression was performed for each effect size and adverse events, sensitivity analysis, cumulative analysis along with the analysis of ratio of means (ROM) in the placebo group. A total of 42 studies were included in this study for review, and a total of 37 studies were included in the meta-analysis, including a total of 23395 patients (treatment group: 11392, placebo group: 12003). The effect size of all variables except PVR showed a significant improvement following 5ARI treatment compared with placebo. However, the effect size of differences showed declining trend in PV, IPSS and Qmax according to recent years of publication. In ROM analysis, PV showed no significant increase in the placebo group, with a ROM of 1.00 (95% CI, 0.88, 1.14). The 5ARI treatment resulted in a significantly higher incidence of decreased libido (OR = 1.7; 95% CI, 1.36, 2.13), ejaculatory disorder (OR = 2.94; 95% CI, 2.15, 4.03), gynecomastia (OR = 2.32; 95% CI, 1.41, 3.83), and impotence (OR = 1.74; 95% CI, 1.32, 2.29). Our study has the following limitations: included studies were heterogeneous and direct comparison of efficacy between alpha blocker and 5ARI was not performed. Adverse events including depression or suicidal attempt could not be analyzed in this meta-analysis setting. CONCLUSIONS: Although there was a significant clinical benefit of 5ARI monotherapy compared with placebo, the effective size was small. Moreover, the risk of adverse events including sexually related complications were high. Additional head-to-head studies are needed to re-evaluate the clinical efficacy of 5ARI compared with alpha-adrenergic receptor blockers. FAU - Kim, Jae Heon AU - Kim JH AUID- ORCID: 0000-0002-4490-3610 AD - Department of Urology, Stanford University Medical Center, Stanford, CA, United States of America. AD - Department of Urology, Soonchunhyang University Hospital, Soonchuhyang University Medical College, Seoul, Korea. FAU - Baek, Min Jung AU - Baek MJ AD - Department of Obstetrics and Gynecology, CHA Bundang Medical Center, Seongnam, Korea. FAU - Sun, Hwa Yeon AU - Sun HY AD - Department of Urology, Soonchunhyang University Hospital, Soonchuhyang University Medical College, Seoul, Korea. FAU - Lee, Bora AU - Lee B AD - Department of Statistics, Graduate School of Chung-Ang University, Seoul, Korea. FAU - Li, Shufeng AU - Li S AD - Department of Urology and Dermatology, Stanford University Medical Center, Stanford, CA, United States of America. FAU - Khandwala, Yash AU - Khandwala Y AD - Department of Urology, Stanford University Medical Center, Stanford, CA, United States of America. AD - University of California, San Diego School of Medicine, San Diego, CA, United States of America. FAU - Del Giudice, Francesco AU - Del Giudice F AUID- ORCID: 0000-0003-3865-5988 AD - Department of Urology, Sapienza University of Rome, Rome, Italy. FAU - Chung, Benjamin I AU - Chung BI AD - Department of Urology, Stanford University Medical Center, Stanford, CA, United States of America. LA - eng GR - T32 DK007357/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't DEP - 20181003 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (5-alpha Reductase Inhibitors) RN - 0 (Adrenergic alpha-Antagonists) RN - EC 3.4.21.77 (Prostate-Specific Antigen) SB - IM MH - 5-alpha Reductase Inhibitors/adverse effects/*therapeutic use MH - Adrenergic alpha-Antagonists/adverse effects/therapeutic use MH - Aged MH - Drug Therapy, Combination/adverse effects MH - Erectile Dysfunction/chemically induced/physiopathology MH - Humans MH - Libido/drug effects MH - Male MH - Middle Aged MH - Prostate-Specific Antigen/blood MH - Prostatic Hyperplasia/blood/complications/*drug therapy/pathology PMC - PMC6169865 COIS- The authors have declared that no competing interests exist. EDAT- 2018/10/04 06:00 MHDA- 2019/03/07 06:00 PMCR- 2018/10/03 CRDT- 2018/10/04 06:00 PHST- 2018/04/23 00:00 [received] PHST- 2018/08/21 00:00 [accepted] PHST- 2018/10/04 06:00 [entrez] PHST- 2018/10/04 06:00 [pubmed] PHST- 2019/03/07 06:00 [medline] PHST- 2018/10/03 00:00 [pmc-release] AID - PONE-D-18-12170 [pii] AID - 10.1371/journal.pone.0203479 [doi] PST - epublish SO - PLoS One. 2018 Oct 3;13(10):e0203479. doi: 10.1371/journal.pone.0203479. eCollection 2018.