Urethral bulking therapy for treating stress urinary incontinence in women

Description of the condition

Urinary incontinence (UI) is defined as the complaint of involuntary loss of urine (Haylen 2010). It can affect women of all ages and is more prevalent with increasing age, particularly after the age of 70, but with a peak in prevalence around 50 to 54 years of age (Hannestad 2000). The prevalence of UI varies among studies due to differences in definitions of UI, the target populations studied and sampling strategies. 

This review focuses on stress urinary incontinence (SUI), defined as the involuntary loss of urine on effort or physical exertion (e.g. sporting activities) or on sneezing or coughing (Haylen 2010). SUI is the most prevalent subtype of UI, accounting for around half of all cases of UI (Ebbesen 2013). Risk factors for developing SUI other than age include pregnancy, childbirth (Gyhagen 2019), high body mass index (BMI) and high‐impact training among others (Almousa 2018).

The pathophysiology of SUI is not completely understood (Cundiff 2004). Some theories  suggest that it could result from a lack of urethral support, or urethral hypermobility, which causes a looseness in the pelvic floor ((DeLancey 1996; Petros 1990). Thind 1994 suggests that SUI could result from a weakness in the urethral sphincter (termed intrinsic sphincter deficiency (ISD)), which can be caused by age‐related reduction of muscle mass, decreased vascularisation by postmenopausal status or nerve damage around the perineum. More recently, de Vries 2018a suggests that the active reflex mechanism of the urethra also plays an important role. To ensure continence, the active closure mechanism of the urethra is reliant on sufficient midurethral support and a good anatomical position.

The personal burden of UI can be substantial. Qualitative studies on women’s perceptions of UI describe feelings of anxiety, emotional distress, isolation, stigmatisation, shame, self‐blame and a sense of impairment. As a consequence, women impose various restrictions on their daily lives, such as selecting their clothes to disguise staining, knowing where toilets are located when planning activities in public places and restricting fluid intake. Some avoid places, activities or hobbies to prevent potential embarrassment (Siddiqui 2014). Moreover, UI may have an impact on intimacy and sexual relationships, with women experiencing decreased sexual desire, dyspareunia and feelings of guilt and blame from coital incontinence (Mendes 2017).

The physical and psychosocial impact of UI on a woman’s life can be severe and result in a significantly lower quality of life (Murukesu 2019). It is therefore a big public health problem that brings major costs. In the US, the annual direct cost of UI in women in 1995 was US dollars (USD) 12.4 billion, with 85% of this attributed to SUI (Coyne 2014).

Description of the intervention

Non‐surgical treatments are the first‐line options for SUI. These include lifestyle interventions including weight loss (Imamura 2015); exercises such as pelvic floor muscle training (PFMT), with or without biofeedback (Dumoulin 2018; Herderschee 2011); pharmaceutical therapies such as oestrogen (Cody 2012) and anti‐incontinence devices such as weighted vaginal cones (Herbison 2013). Surgical interventions are offered to patients when first‐line options have not resulted in sufficient improvement. International guidelines recommend the following surgical options: colposuspension (open or laparoscopic) (Freites 2019; Lapitan 2017), midurethral mesh sling (Ford 2017), autologous fascial pubovaginal sling (Saraswat 2020), and urethral bulking therapy (Kirchin 2017). The choice of treatment depends on several factors, including the patient’s expectations and goals, and the individualised risks and benefits. Patient decision aids have been put forward to stimulate shared decision‐making and ensure that patients are well‐informed about specific complications associated with each surgical procedure. This is particularly relevant following current concerns about the safety of mesh surgery for urogynaecological patients (FDA 2008).

Urethral bulking therapy is a minimally invasive treatment option for SUI. It has several benefits in comparison to other surgical options, including that it can be performed under local analgesia in an outpatient setting and that it has a shorter recovery period. During the procedure, material is injected just underneath the mucosa of the urethra. In some procedures, the bulking agent is injected through the vaginal wall (e.g. Urolastic™), while in others the injection is made via the urethral lumen (e.g. Bulkamid®, Macroplastique™). In each case, the aim is to place several deposits of the bulking agent in the urethral submucosa between the midurethral level and the bladder neck. The number of injections and volume of bulking agents employed vary between and within bulking therapies. Prior to patient discharge, post‐void residual volume must be recorded. Catheterisation may be necessary for urinary retention.

After the procedure, patients may have a bruised feeling, haematuria or painful micturition for a few days and may have a period of lifestyle restrictions (e.g. avoiding heavy lifting, physical exercise and swimming). It is common for patients to undergo repeat injections over time to accomplish satisfactory results. The number of reinjections varies widely between (or across) studies. Results of a systematic review showed reinjection rates of polyacrylamide hydrogel (Bulkamid®) and polydimethylsiloxane (Macroplastique™) to be between 5% to 65% and 9% to 44% respectively (Siddiqui 2017). The most common adverse events associated with urethral bulking agents are urinary retention, transient haematuria, dysuria, pain, dyspareunia, urinary tract infections, urgency incontinence and extrusion, exposure or erosion of the bulk material (de Vries 2018b).

Since the first bulk injections for women with SUI were performed in 1938, different bulking agents have been introduced to the market. However, the following bulking agents have been withdrawn due to serious adverse events: Zuidex™, due to the formation of pseudo‐abscesses (Lightner 2009); Teflon™ due to migration of particles (Malizia 1984); autologous fat due to pulmonary embolisms (Lee 2001); Tegress™ and Uryx™ due to urethral erosion (Hurtado 2009); and Contigen™ due to skin reactions. Currently, six urethral bulking agents for SUI are available (see Appendix 2). The material used for bulking agents varies among manufacturers and can be divided roughly into synthetic material (e.g. silicon particles, hydrogel) or biological material (e.g. collagen). Most synthetic materials consist of particles suspended in a biodegradable carrier gel, although some have a nonabsorbable homogenous structure.

Urethral bulking therapy is often offered to older women, women with comorbidities or with a high BMI; or after unsuccessful surgery, as these characteristics can hinder operational techniques or increase the chance of complications. Although little evidence is available concerning whether these patient groups benefit most from urethral bulking therapy, one post‐hoc analysis of a randomised controlled trial (RCT) that compared bulking agents hydrogel (Bulkamid®) and collagen gel (Contigen™) showed that older patients aged over 60 were more likely to be cured, compared to younger women (Elmelund 2019).

How the intervention might work

Urethral bulking therapy aims to improve sphincter function by increasing the co‐aptation of the urethral mucosa. The bulking material creates a filler that reduces the diameter of the lumen and increases flow resistance, thereby preventing leakage in patients with SUI.

Why it is important to do this review

It is important to determine whether there is evidence to justify any repositioning of urethral bulking therapy in patient pathways, particularly in light of recent clinical, medico‐legal and political concerns about midurethral mesh sling operations. In addition to updating the evidence and methodology in the previous Cochrane Review in this area (Kirchin 2017), this review will also include a brief economic commentary on costs and cost‐effectiveness (Aluko 2020).