Preoperative hormonal stimulation effect on hypospadias repair complications: Meta-analysis of observational versus randomized controlled studies

Summary Introduction Preoperative hormonal stimulation (PHS) is commonly administered to improve hypospadias outcomes. However, current literature provides no clear evidence to support its use, and controversies exist regarding its effect on postoperative complications. Herein we systematically evaluate the effect of PHS on postoperative complications rates following hypospadias repair. Materials and methods Comprehensive literature search performed on April 2016 including OVID MEDLINE, EMBASE, Web of Science, Cochrane Library, Clinicaltrials.gov , World Health Organization (WHO) International Clinical Trial Registry Platform (ICTRP), and ProQuest. Study quality assessment followed the Cochrane collaboration recommendation using risk of bias assessment, ROBINS-I and NOQAS. Effect estimates were extracted as relative risk (RR) with 95% confidence interval (CI) and pooled using Mantel-Haenzel method. Evidence quality was assessed using GRADE approach. Protocol Registration: PROSPERO CRD42016037881. Results Twenty-one publications from 16 trials examining the effect of androgenic PHS on postoperative outcome were included. Subgroup analysis based on study design (including nine cohort studies with moderate to high risk of bias for patient selection) showed no significant difference on postoperative outcomes (RR 1.31, 95% CI 0.95–1.81) (table). Pooled effect estimates with moderate quality of evidence from three randomized controlled trials suggest that significant lesser postoperative complications occur among patients exposed to PHS (RR 0.36, 95% CI 0.20–0.65). Uniformly, the reported adverse effects related to PHS were mild and transient, with good overall tolerance. Conclusions Effect estimates generated from the better quality of evidence showed that PHS may decrease postoperative complications following hypospadias repair. Future studies should aim at identifying indicated subgroup of patients that will benefit from it and standardizing the dose and mode of delivery for best clinical result. Table . Summary of relative risk and corresponding 95% CI according to study design. No. of studies Relative risk for postoperative complication 95% CI Randomized controlled trials 3 0.36 0.20–0.65 Cohorts 9 1.31 0.95–1.81 Total 12 0.99 0.63–1.55