Stress urinary incontinence (SUI) remains a common, bothersome, and costly condition affecting up to 25% of women.¹ Our understanding of the pathophysiology of SUI has evolved from theories surrounding anatomical influences to theories of pressure transmission and then more recently to sphincteric theories, particularly in recognizing the 2 overlapping mechanisms of urethral hypermobility and intrinsic sphincter deficiency (ISD). Traditional treatments of SUI, including retropubic suspensions, had high failure rates in those with fixed urethras (and ISD). Thus, the presence of ISD became the standard prerequisite for use of urethral bulking agents (UBAs). This was in part because UBAs were initially indicated for patients who had failed “traditional” incontinence surgeries and were an attractive, less morbid option for elderly, frail patients with fixed urethras.^2,3

Insurance companies defaulted to requiring ISD as a diagnosis to approve reimbursement for bulking starting in the 1990s. However, there was limited evidence that ISD was needed for urethral bulking success. Additionally, there was no validated correlation of hypermobility and the presence or degree of SUI. As such, the most recently updated AUA/Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction Guidelines do not require a diagnosis of ISD or urodynamic studies prior to administration of UBA.⁴ The consensus among all major guidelines (AUA, Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction, European Association of Urology, and American Urogynecologic Society) is that UBA is a low-risk procedure that should be offered to women with SUI, although with the understanding that their efficacy is lower than other SUI surgical procedures and repeat injections are often needed to maintain effect (Figure 1).

Typically, bulking can be done in the office, under local anesthesia, and transurethrally through a scope, although it may be offered in the operating room under sedation as well. The quantity and number of cushions depends on the agent and surgeon preference. Comparative data on injection volume, location, and technique are still limited. Depending on the agent, the cushions are usually designed to be administered at the mid urethra or bladder neck (Figure 2).³

Bulking agents have included various compounds that have been used and developed throughout the years. The 2 main classes of UBAs are particulate and nonparticulate agents. Particulate agents are made from solid microparticles in an absorbable liquid or gel carrier and include polydimethylsiloxane (Macroplastique), carbon-coated zirconium oxide (Durasphere), and calcium hydroxyapatite (Coaptite). Except for calcium hydroxyapatite, the particles are nondegradable and achieve their long-term bulking effect through reactive tissue changes after the carrier volume is absorbed. Conversely, polyacrylamide hydrogel (PAHG) is the only widely used and commercially available nonparticulate UBA for SUI. PAHG achieves its bulking effect through the injected gel’s volume, which is nonabsorbable and anchored in place by a network of host tissue fibers.⁵ Although there are limited comparative data, PAHG has been shown to have fewer adverse effects compared with particulate agents, including foreign body granulomas, loss bulk, erosion, migration, and material extrusion.⁵

In general, the ideal properties of a bulking agent include those that are nonimmunogenic, hypoallergenic, biocompatible, nonmigratory, and durable.⁵ Newer biologic agents in development include stem cell therapy to derive muscle, adipose, bone marrow, and other tissues in the treatment of SUI. In considering these newer modalities, it will be important to understand myriad factors: which cell types have the best ability to differentiate, the ideal dose of the agent, procedural frequency, methods of injections, and the commercial and financial viability of these options.

In terms of outcomes, UBAs are often associated with good durability and patient satisfaction, although they fall short in curative response of SUI compared with midurethral sling.^6-8 In a randomized trial between tension-free vaginal tape (TVT) and PAHG, with the primary outcome of patient satisfaction and the secondary outcomes of effectiveness in reducing urinary leakage and overall complications, TVT was found to yield significantly higher patient satisfaction and cure rates than PAHG at 1-, 3-, and 5-year follow-up, while PAHG was associated with fewer perioperative and postoperative complications.^6-8 At the 5-year follow-up, visual analogue scale satisfaction scores of > 80 and 100 were reached in 93% and 75% of participants in the TVT and PAHG arms, respectively. Objective cure measured by a negative cough stress and pad stress test was reached in 66% women in the TVT group and 48% women in the PAHG group.⁸

Despite these differences in outcomes and the widespread adoption of sling procedures in the 2000s and 2010s, urethral bulking has still proven to be an effective and popular option for women with SUI. After several public controversies surrounding mesh slings, including a Food and Drug Administration order to stop distribution of vaginally placed mesh for prolapse repair, patient and provider preference for UBAs significantly increased in the 2010s and 2020s.^9,10 Although the use of mesh for prolapse has demonstrated improved safety profiles, UBA continues to demonstrate faster growth in recent years compared with the midurethral sling for SUI treatment.¹⁰

In women with ISD and a fixed urethra, frail patients, and those wishing to avoid the anesthesia, recovery, and postoperative restrictions associated with sling placement, urethral bulking can still be considered a treatment option. Guidelines now also suggest that UBA can be offered as a primary procedure for the treatment of most cases of SUI after appropriate counseling. As discussed in the updated AUA Guidelines, physicians should discuss SUI recurrence and the likely need for future injections with their patients prior to treatment. At this time, PAHG demonstrates marginally improved safety and durability data over other UBA options.³ However, further investigation should continue to pursue possible new agents, as well as expand our knowledge on existing UBAs, in order to achieve excellent safety, efficacy, and cost efficiency for our patients with SUI.

Conflicts of Interest: Dr Brucker reported being an advisor, speaker, and grant recipient of Boston Scientific; a speaker and advisor investigator for Abbvie; an educational grant recipient of Medtronic; an advisor for Watkins Conti; and an advisor, speaker, and investigator for Sumitomo Pharma. No other disclosures were reported.