Fowler’s syndrome, characterised by a primary disorder of urethral sphincter relaxation, is an uncommon cause of urinary retention in young women. The voiding dysfunction in Fowler’s syndrome can be difficult to manage with intermittent self-catheterisation and the most efficacious treatment sacral neuromodulation, though this is not widely available. Urethral sphincter botulinum toxin injection has been shown to improve voiding function in non-neurogenic patients though remains an off-label treatment. Although an open label study in Fowler’s syndrome demonstrated improvement in urine flowrate, PVR and urethral pressure profile measurements, as well as patient reported satisfaction after 10 weeks (1), the sole randomised control trial in neurogenic and non-neurogenic patients investigating urethral sphincter botulinum toxin injections was reported to be a negative study (2). There is the need for an alternative treatment for Fowler's syndrome with urethral sphincter botulinum toxin injection to be validated with long-term outcomes.

In this long-term follow-up study, 33 female patients with a primary disorder of urethral sphincter relaxation (Fowler’s syndrome) presenting with voiding dysfunction and urinary retention were reviewed retrospectively from a single tertiary referral centre between March 2010 and December 2021. The treatment was offered to females meeting diagnostic criteria for Fowler’s Syndrome (abnormal concentric needle EMG of the striated urethral sphincter and/or abnormally elevated urethral pressure profile) deemed suitable for this treatment following a multidisciplinary team discussion. Exclusion criteria were a history of urethral surgery, stress urinary incontinence, a neurological cause of abnormal sphincter function, pregnancy, current urinary tract infection, or prescribed anticoagulants. All patients were counselled of the possible adverse events related to botulinum toxin injection (transient stress urinary incontinence, pain and bleeding), and provided written consent. In the supine position, 1mL of 2% lidocaine was injected on either side of the external urethral meatus, followed by 100 units of OnabotulinumtoxinA (BotoxTM; Abvie, Irvine, CA, USA), dissolved in 2 mL saline injected transperineally into the striated urethral sphincter divided on either side at the 3 and 9 o’clock position. Patients were reviewed at four weeks after injection and assessed for treatment efficacy.

33 female patients with a mean age of 30.2 years received 165 unique urethral sphincter botulinum toxin injections over the study period. 58% of patients presented in acute urinary retention, and 85% were reliant on a form of catheterisation. 71% (n=22) patients had electromyographic (EMG) evidence diagnostic of Fowler’s syndrome. Urodynamic studies (n=24 had baseline urodynamic studies) demonstrated abnormal sensation in 48% patients and detrusor underactivity was identified in 56% (n=14) patients at baseline. The mean MUCP at baseline was raised at 105.5±4.7 cm H2O, compared with the mean expected MUCP of 59.4±3.8 cm H2O.

64% of patients responded to botulinum toxin injections. Botulinum toxin responders had a significantly raised baseline maximum urethral closure pressure, compared to non-responders. Baseline mean MUCP was significantly higher in the responder group compared to the non-responder group (114±4.5cm H2O versus 87.4±8.7 cm H2O respectively, p=0.004).  15 patients received more than one botulinum toxin injection, at a median interval of 112 days. Side effects were reported in 11.5% of injections.

Our study is the longest observational review of urethral sphincter botulinum toxin injections in Fowler’s syndrome over 11 years. We showed that transperineal injection of botulinum toxin into the urethral sphincter was associated with an improvement in voiding dysfunction in 64% of female individuals with Fowler’s syndrome. Patients who had a higher MUCP at baseline were significantly more likely to respond to botulinum toxin injection.

Due to the relative rarity of Fowler’s syndrome, a large long-term cohort study is required to validate the outcomes of urethral sphincter botulinum toxin injections. We demonstrated that transperineal urethral sphincter botulinum toxin injection is effective in 64% of patients with voiding dysfunction secondary to Fowler’s syndrome. It is a well-tolerated procedure, with a low rate (11.5%) of transient adverse events and after 11 years no safety concerns.  A significantly high MUCP in responders suggest that this treatment is effective in those with urethral sphincter dysfunction and hence patient selection is key. Urethral sphincter botulinum toxin injections provide a low-cost, less invasive, widely available treatment alternative to treat voiding dysfunction in Fowler’s syndrome.

Panicker JN, Seth JH, Khan S, et al. Open-label study evaluating outpatient urethral sphincter injections of onabotulinumtoxinA to treat women with urinary retention due to a primary disorder of sphincter relaxation (Fowler’s syndrome). BJU Int. Blackwell Publishing Ltd; 2016;117:809–813.
Onabotulinumtoxin a urethral sphincter injection as treatment for non-neurogenic voiding dysfunction - A randomized, double-blind, placebo-controlled study. Sci Rep [online serial]. Nature Publishing Group; 2016;6:1–9. Accessed at: http://dx.doi.org/10.1038/srep38905.

Continence 7S1 (2023) 101002
DOI: 10.1016/j.cont.2023.101002