St George’s Hospital
Urinary incontinence is a common condition in men and women, which causes significant morbidity in sufferers and a great financial expense to healthcare providers. The embarrassing nature of the condition means patients are often reluctant to seek medical help and there is underreporting.
Incontinence can be subdivided into urge incontinence due to involuntary contractions of the bladder muscle (detrusor overactivity) during filling, and stress urinary incontinence due to a weak urethral sphincter mechanism that is overcome by increases in bladder pressure secondary to physical activity. The treatment of urge incontinence is primarily pharmacological, and the search for a bladder- specific anticholinergic goes on. Treatment of stress urinary incontinence is commonly surgery. New, less invasive surgical techniques are being developed. In addition, new intravaginal and intraurethral devices are becoming available. There is no pharmacological agent with a license to treat stress urinary incontinence at the present time.
Urge incontinence secondary to an overactive bladder (OAB) has traditionally been treated either by bladder retraining (behavioural therapy) or pharmacologically. Various drugs are available that claim to successfully alleviate detrusor overactivity (OAB is a symptomatic diagnosis in patients with urgency or urge urinary incontinence suggestive of detrusor overactivity). The majority have antimuscarinic activity and produce inevitable unwanted effects, which the clinician must balance against any perceived benefit. These antimuscarinic effects typically produce dry mouth, difficulty in visual accommodation, constipation and somnolence. They should therefore be avoided in patients with obstructive uropathy, bowel obstruction, ulcerative colitis, narrow angle glaucoma, myasthenia gravis or severe cardiovascular disease.
Oxybutynin is still the most common treatment prescribed for OAB in the UK, and is given in two- or three-times daily doses, titrating benefit with side-effects. Tolterodine is a new antimuscarinic agent that offers equipotent effects in the bladder, compared with oxybutynin, but lower affinity for muscarinic receptors in the salivary gland. Data so far suggest that this drug is better tolerated and is associated with higher patient compliance than oxybutynin.(1) No antimuscarinic so far developed is specific for the bladder only, and the search for a bladder-specific muscarinic receptor goes on.
The year 2000 saw an extended-release oxybutynin preparation being licensed in the UK for the treatment of OAB. This modified preparation seeks to avoid the peak plasma levels seen after dosing with immediate- release oxybutynin and therefore to reduce side-effects. Initial trials seem encouraging.(2)
Recent evidence suggests that the side-effects of oxybutynin may be related to high levels of its metabolite, N-desethyl-oxybutynin.(3) Winkler and Sand offered oxybutynin suppositories to 25 women with an unstable detrusor (idiopathic detrusor overactivity) who had not tolerated oral antimuscarinics.(4) A total of 48% responded to the suppositories, and 58% of these continued to use them for at least 90 days.
Theoretically, parenteral administration should avoid first-pass metabolism in the liver and may therefore be associated with less side-effects. There are currently trials investigating the use of oxybutynin skin patches as well as an intravesical, continuous-release drug delivery system.(5)
Stress urinary incontinence
Stress urinary incontinence is the most common cause of incontinence in women, whereas urge incontinence is more common in men. Initial treatment of incontinence normally comprises weight reduction, smoking cessation and pelvic floor exercises. This will provide satisfactory improvement in 30% of women.
At present there is no pharmacological agent licensed for the treatment of stress urinary incontinence. The urethral sphincter musculature does contain a-adrenergic receptors and, in theory, alpha-agonist agents should produce an increase in sphincter tone and thus improve stress incontinence. There are several such agents in development, and the results of placebo-controlled randomised trials are awaited.
Women who fail to respond to conservative measures and who request further, non-surgical treatment, can be considered for a variety of devices, either intravaginal or intraurethral. The Conveen Continence Guard(™) (Coloplast Ltd) is an example of an intravaginal device (see Figure 1). The shape of it is such that, when it is placed in the vagina, it supports the bladder neck and thus prevents or reduces leaking during physical activity. Sander et al. assessed its effect on urinary leakage and quality of life in 55 women.(6) Forty-one (74.5%) completed the 3-month study. The 14 women who withdrew did so because of local discomfort or problems retaining the device. The mean urinary pad test leakage with the device in place decreased significantly from 77.5g to 23.5g per 24 hours. The Quality of Life (QoL) score measured by the incontinence impact questionnaire improved significantly after 3 months’ use. Despite their efficacy, such intravaginal devices are not available on prescription in the UK. Women using the Continence Guard must purchase it from the manufacturer at a cost of £42.54 for a 30-day supply. This cost would be prohibitive to many women, and perhaps action should be taken to allow such products to be prescribed.
Surgery should be considered when conservative measures fail, and the type of repair should be chosen on the basis of presumed pathophysiology (suspension for bladder neck and urethral hypermobility, and sling or urethral bulking for internal sphincter deficiency). There are several options. The transvaginal tape (TVT) is a “new” suburethral sling procedure. It can be performed as a day case under local or spinal anaesthesia, and recovery time is more rapid than for a conventional open colposuspension. The use of TVT is rising in popularity across Europe, probably because of the simple nature of the procedure and the success rates. The first good-quality randomised controlled trial comparing TVT with open colposuspension has reported 6-month follow-up data, which suggest that the two are comparable in success.(7)
Urethral bulking therapy is a surgical option as a primary or secondary procedure for the treatment of mild stress incontinence or for those unfit for more major surgery. The bulking agent is injected periurethrally or transurethrally under the submucosa to bulk the tissues around the bladder neck. The procedure is performed under local or regional anaesthetic, and the most common bulking agent is glutaraldehyde cross-linked bovine collagen. A small number of patients are allergic to bovine collagen, so a skin allergy test must be performed 1 month before treatment. Collagen is expensive and biodegradable, which may contribute to the deterioration in success rates from 65% in the short term to 30–45% after 2 years. New synthetic materials are being developed and tested that will, it is hoped, be cheap, easy to use, non-allergenic and have better long-term cure rates.
Increased awareness about effective therapies for the treatment of urinary incontinence has led to incontinence becoming a more common reason for referral to hospital departments. It is essential that we continue to develop treatments that are effective with few side-effects and which are acceptable to patients. It is also time to consider changes in continence product provision that will allow a greater number of people access to them.
- Appell RA. Clinical efficacy and safety of tolterodine in the treatment of overactive bladder: a pooled analysis. Urology 1997;50 Suppl 6A:90-6.
- Anderson R, Mobley D, Blank B, Saltzstein D, Susset J, Brown J. Once daily controlled versus immediate release oxybutynin chloride for urge urinary incontinence. J Urol 1999;161:1809-12.
- Buyse G, Waldeck K, Verpoorten C, Bjork K, Casaer P, Andersson KE. Intravesical oxybutynin for neurogenic bladder dysfunction: less systemic side effects due to reduced first pass metabolism. J Urol 1998;160:892-6.
- Winkler HA, Sand PK. Treatment of detrusor instability with oxybutynin rectal suppositories. Int Urogynecol J 1998;9(2):100-2.
- Bulmer P, Abrams P. The overactive bladder. Rev Contemp Pharmacother 2000;11:1-10.
- Sander P, Thyssen H, Lose G, Thorup Andersen J. The effect of a vaginal device on urinary leakage and quality of life of women with stress urinary incontinence. Obstet Gynecol 1999;93:407-11.
- Ward KL, Hilton P, Browning J. A randomised trial of colposuspension and tension free vaginal tape (TVT) for primary genuine stress incontinence. Neurourol Urodynam 2000;19(4):386-8.
International Continence Society
Association d’Aide aux Personnes Incontinentes
18–21 Sept 2001
International Continence Society (ICS)
5–8 Dec 2001
International Urogynaecological Association (IUGA)