Urethral injection therapy for urinary incontinence in women

Background Urinary incontinence imposes a significant health and economic burden to society. Periurethral or transurethral injection of bulking agents is a minimally invasive surgical procedure used as one the surgical treatments of stress urinary incontinence (SUI) in adult women. Objectives To assess the effects of periurethral or transurethral injection therapy on the cure or improvement of urinary incontinence in women. Search methods We searched the Cochrane Incontinence Group Specialised Trials Register (searched 8 November 2010) and the reference lists of relevant articles. Selection criteria All randomised or quasi-randomised controlled trials of treatment for urinary incontinence in which at least one management arm involved periurethral or transurethral injection therapy. Data collection and analysis Two review authors independently assessed methodological quality of each study using explicit criteria. Data extraction was undertaken independently and clarification concerning possible unreported data sought directly from the investigators. Main results Excluding duplicate reports, we identified 14 trials (excluding one that was subsequently withdrawn from publication and not included in this analysis) including 2004 women that met the inclusion criteria. The limited data available were not suitable for meta-analysis because they all came from separate trials. Trials were small and generally of moderate quality. One trial of 45 women that compared injection therapy with conservative treatment showed early benefit for the injectable therapy with respect to continence grade (risk ratio (RR) 0.70, 95% confidence interval (CI) 0.52 to 0.94) and quality of life (mean difference MD) 0.54, 95% CI 0.16 to 0.92). Another trial, comparing Injection of autologous fat with placebo, terminated early because of safety concerns. Two trials that compared injection with surgical management found significantly better objective cure in the surgical group (RR 4.77, 95% CI 1.96 to 11.64; and RR 1.69, 95% CI 1.02 to 2.79), although the latter trial data did not reach statistical significance if an intention-to-treat analysis was used. Eight trials compared different agents and all results had wide confidence intervals. Silicone particles, calcium hydroxylapatite, ethylene vinyl alcohol, carbon spheres and dextranomer hyaluronic acid combination gave improvements which were not shown to be more or less efficacious than collagen. Dextranomer hyaluronic acid compound treated patients appeared to have significantly higher rates of injection site complications (16% with the hyaluronic acid compound versus none with collagen; RR 37.78, 95% CI 2.34 to 610.12) and this product has now been withdrawn from the market. A comparison of periurethral and transurethral methods of injection found similar outcomes but a higher (though not statistically significant) rate of early complications in the periurethral group. One trial of 30 women showed a weak (but not clinically significant) advantage for patient satisfaction (data not suitable for analysis in RevMan) after mid-urethral injection in comparison to bladder neck injection but with no demonstrable difference in continence levels. Authors' conclusions The available evidence base remains insufficient to guide practice. In addition, the finding that placebo saline injection was followed by a similar symptomatic improvement to bulking agent injection raises questions about the mechanism of any beneficial effects. One small trial comparing silicone particles with pelvic floor muscle training was suggestive of benefit at three months but it is not known if this was sustained, and the treatment was associated with high levels of postoperative retention and dysuria. Greater symptomatic improvement was observed with surgical treatments, though the advantages need to be set against likely higher risks. No clear-cut conclusions could be drawn from trials comparing alternative agents, although dextranomer hyaluronic acid was associated with more local side effects and is no longer commercially available for this indication. There is insufficient evidence to show superiority of midurethral or bladder neck injection. The single trial of autologous fat provides a reminder that periurethral injections can occasionally cause serious side effects. Also, a Brief Economic Commentary (BEC) identified three studies suggesting that urethral bulking agent might be more cost-effective compared with retropubic mid-urethral slings, transobturator or traditional sling procedure when used as an initial treatment in women without hypermobility or as a follow-up to surgery failure provided injection is kept minimal. However, urethral bulking agent might not be cost-effective when compared with traditional sling as an initial treatment of SUI when a patient is followed up for a longer period (15 months post-surgery).