Urethral Syndrome

Urethral syndrome is a symptom complex of dysuria, urinary frequency and urgency, with suprapubic or urethral discomfort, in the absence of a positive conventional urine culture, other identifiable cause, or structural abnormality. It is also called the "urethral syndrome" or "female urethral syndrome" and is a diagnosis of exclusion; in men a similar picture raises prostatitis or urethritis.

• Mostly women aged 20 to 50. Many women with these symptoms have "sterile pyuria" or low count bacteriuria (fewer than 10^5 but 10^2 to 10^4 CFU/mL of a uropathogen), which is clinically significant when symptomatic.
• Causes to look for:
  • Infective: Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Ureaplasma urealyticum, Trichomonas vaginalis, herpes simplex virus, Candida, low count coliform infection, urinary tuberculosis (sterile pyuria).
  • Non-infective: genitourinary syndrome of menopause (atrophic urethritis and vaginitis), urethral caruncle, urethral diverticulum, urethral stenosis, chemical irritants (soaps, bubble baths, spermicides, vaginal douches, feminine hygiene sprays), trauma from intercourse, interstitial cystitis (bladder pain syndrome), stones, tumours, pelvic floor hypertonia, psychosomatic factors.
• Chronic or recurrent course in some patients and a significant effect on quality of life.

• Dysuria (often at the start), frequency, urgency, suprapubic or perineal pain, dyspareunia, post-void discomfort, a feeling of incomplete emptying; often relapsing; no fever or loin pain.
• Ask about sexual history, new partner, discharge, vaginal dryness, menopausal status, contraception, irritant products, recent antibiotics, stones, haematuria, pelvic pain, bowel symptoms, anxiety.
• Examination: abdomen, pelvic examination (vulvar dermatoses, discharge, atrophy, urethral meatus, prolapse), urethral tenderness or mass on palpation of the anterior vaginal wall, pus at the meatus on pressing (urethral diverticulum), pelvic floor tone and tenderness.
• Red flags: visible haematuria, persistent microscopic haematuria, fever, rigors, loin pain, immunosuppression, pregnancy, suspected tuberculosis, urinary retention, recurrent episodes despite treatment.

• Urinalysis (nitrites, leucocyte esterase, blood) and midstream urine culture (report counts of 10^3 CFU/mL or more in symptomatic women).
• Nucleic acid amplification tests for chlamydia, gonorrhoea, Mycoplasma genitalium and Trichomonas on a first void urine or vulvovaginal swab; high vaginal swab for Candida and bacterial vaginosis; herpes PCR if lesions.
• Early morning urines (three consecutive) for acid fast bacilli if sterile pyuria persists.
• Pregnancy test; glucose.
• Renal tract ultrasound with post-void residual; flexible cystoscopy if haematuria persists, symptoms are recurrent, or diverticulum or interstitial cystitis is suspected; pelvic MRI for urethral diverticulum.
• Differential: acute cystitis, vulvovaginitis, genitourinary syndrome of menopause, interstitial cystitis, overactive bladder, herpes.

• Treat any identified cause:
  • Chlamydia: doxycycline 100 mg orally twice daily for 7 days. Gonorrhoea: ceftriaxone 1 g intramuscularly single dose (with partner notification). Mycoplasma genitalium: doxycycline 100 mg twice daily for 7 days followed by moxifloxacin 400 mg daily for 7 days (or azithromycin 1 g then 500 mg daily for 2 days after resistance testing).
  • Trichomonas: metronidazole 400 to 500 mg orally twice daily for 7 days. Candida: fluconazole 150 mg orally as a single dose. Herpes simplex: aciclovir 400 mg orally three times daily for 5 to 7 days (valaciclovir 500 mg twice daily for 5 days).
  • Low count bacteriuria with symptoms: a 3 day course of nitrofurantoin 100 mg modified release orally twice daily (or fosfomycin 3 g single dose) guided by the culture result.
  • Genitourinary syndrome of menopause: estradiol 10 microgram vaginal tablet nightly for 2 weeks, then twice weekly; or estriol 0.1 percent cream 0.5 g nightly for 2 weeks, then twice weekly.
• Remove irritants: avoid soaps, bubble baths, douches, spermicides, scented products; use plain water and an emollient wash.
• Symptomatic: ibuprofen 400 mg orally three times daily with food for up to 5 days; paracetamol 1 g every 6 hours; phenazopyridine is not available in all countries; alkalinising agents have no proven benefit.
• Pelvic floor muscle relaxation exercises and physiotherapy for hypertonic pelvic floor; bladder training.
• Chronic cases with sterile urine: amitriptyline 10 mg orally at night increased every 1 to 2 weeks up to 50 mg; or gabapentin 300 mg at night titrated to 900 to 1800 mg per day in divided doses. Refer for interstitial cystitis assessment.
• Urethral diverticulum or caruncle: urology or gynaecology referral for excision.
• Review at 2 to 4 weeks; avoid repeated empirical antibiotics for sterile urine.