Urethritis in Men

Urethritis describes urethral inflammation and can be the result of infectious or noninfectious causes but is primarily a sexually acquired disease.

Urethritis can be diagnosed if any of the following are present:

• Mucopurulent or purulent discharge from urethral meatus.
• Gram stain of urethral smear showing >5 polymorphonuclear (PMN) cells per high power field. This is the preferred test as it is rapid, highly sensitive and specific for both nonspecific urethritis and gonorrhoea in asymptomatic men.¹
• First pass urine (FPU) positive for >10 PMN per high power field. Some advocate the use of positive leucocytes in FPU - but the sensitivity is low.

1. Gonococcal urethritis - caused by Neisseria gonorrhoeae.³
2. Nongonococcal urethritis (NGU) - caused by a number of organisms other than N. gonorrhoeae.
3. Persistent or recurrent urethritis - 20-60% cases treated for NGU.¹ Probable multifactorial causes but usually no identifiable cause. However, Mycoplasma genitalium (quite often and up to 40% of cases), Ureaplasma urealyticum (tetracycline-resistant) , and Trichomonas vaginalis have been implicated.²

Causes of nongonococcal urethritis^1,2,4,5

• Chlamydia trachomatis (40%)⁶
• U. urealyticum (10-20%)
• M. genitalium (10-20%)
• T. vaginalis (1-17%)
• Rarer infective causes:
  • Urinary tract infection (fewer than 6%)²
  • Adenoviruses (2-4%)
  • Herpes simplex viruses (2-3%)
  • Occasionally, Candida spp., Haemophilus spp., Neisseria meningitidis, E.coli infection, bacteroides infection
• Noninfective causes of NGU include:²
  • Trauma (for example, catheterisation)
  • Irritation (from, for example, soap, spermicidal creams and deodorants)
  • Urethral stricture
  • Other inflammatory conditions (including lichen sclerosus et atrophicus, Stevens-Johnson syndrome, reactive arthritis, Reiter's syndrome)
  • Urinary calculi and foreign body
• No obvious cause 20-30%

• Urethritis is the most common condition diagnosed and treated in men attending genitourinary medicine (GUM) clinics in the UK. Over 80,000 cases are diagnosed every year.
• Nongonococcal urethritis (NGU) is more common than gonococcal urethritis.
• Chlamydia has been estimated currently to infect 5-10% of sexually active women under the age of 24 and men aged between 20-24.⁶ The diagnoses of chlamydial infections have increased in both heterosexual and homosexual men.²
• Persistent or recurrent urethritis occurs in 10-20% of men treated for NGU.²
• Gonorrhoea is most common in men aged 20-24 years and rates of diagnosis in GUM clinics increased between 1994-2002. However, recently the numbers have reduced.²

• May be asymptomatic (10% of patients with gonorrhoea and 50% of patients with chlamydial infections).²
• Urethral discharge - mucopurulent or purulent; with or without blood; more noticeable after holding urine overnight and more common in gonococcal infection⁴. May have gone unnoticed by the patient and be seen only on examination.²
• Urethral pruritus, dysuria or penile discomfort with a risk of sexually transmitted infection (sexually active and has not used a condom or has recent new sexual partner).²
• Other symptoms associated with the cause, e.g. skin lesions in herpes simples virus.
• Systemic symptoms if involvement of other organs, e.g. conjunctivitis or arthritis

Examination may be normal or may reveal haematuria and/or lymphadenopathy.

There is currently a national screening programme for chlamydia.⁶

Identify high-risk patients^2,7

• Sexually active
• Male
• Unprotected vaginal sex
• Homosexual or bisexual
• More common in cities
• Age <35-40 years
• Recent partner change

Ideally this should be performed in a GUM clinic with available microscopy and medications - for direct observation of treatment (DOT).² In a GUM clinic the following will be done:

• Urethral smear - urethritis confirmed if on microscopy there are >5 polymorphonuclear (PMN) lymphocytes per high power field. Microscopy will also reveal Gram-negative intracellular diplococci (GNID) of gonorrhoea.
• FPU - best if patients hold urine for at least four hours prior to the test. Send for nucleic acid amplification test (NAAT) to look for chlamydia and gonorrhoea.
• Pharyngeal and rectal swabs may also be needed.

• Physiological discharge
• Candidiasis
• Cystitis
• Urethral malignancy

Patients with urethritis should be counselled and offered testing for HIV, hepatitis and syphilis.⁹

• Full history including full sexual history.
• Examination: local looking for discharge, skin lesions and systemic examination.
• Refer to GUM clinic if possible.
• Urethral smear for microscopy and/or FPU (both ideally performed if urine held for at least four hours).
• If smear positive - manage as below.
• If smear negative and no definitive evidence of urethritis then defer treatment and re-examine one week later. Also, check mid-stream urine sample for urinary tract infection.
• Screen for other sexually transmitted infections.
• There is some debate as to whether there should be blind treatment of those with symptoms and at high risk of infection or those unlikely to return for follow-up.

Treatment is the same in HIV-negative and HIV-positive patients. Always use local guidelines where possible.

• Nongonococcal urethritis (NGU) - azithromycin 1 gm as single oral dose is first line or doxycycline 100 mg bd for seven days.¹
• Gonococcal urethritis³ - cefixime 400 mg single oral dose or ceftriaxone 250 mg as single IM dose. Quinolones are an alternative provided no resistance.
• Empirical treatment - cover C. trachomatis, e.g. doxycycline 100 mg bd for 7 days or azithromycin 1 gm as single oral dose.

• Need to explain the diagnosis, treatment, adverse effects and importance of completing the course of antibiotics.
• Discuss methods of prevention including advice on safe sex, e.g. condom use.
• Must avoid sexual intercourse until infection cleared up and partner checked out.
• Contact tracing - important to maintain patient confidentiality. Need to trace sexual contacts in the last four weeks and up to six months if asymptomatic (for NGU).

• Patients should be followed up for review at approximately two weeks.
• Take this opportunity to reinforce health education.
• Assess compliance and efficacy.
• Test of cure can also be performed for gonorrhoea, e.g. nucleic acid amplification test (NAAT) or repeat culture 72 hours after treatment has finished. It is not routine for chlamydia unless the patient is pregnant, noncompliance is suspected or re-exposure may have occurred.⁶
• If there are persistent symptoms or persistent urethritis despite being asymptomatic, consider treatment failure, reinfection or infection with an uncommon pathogen, e.g. T. vaginalis. Treat with the original course of antibiotics if the course was not completed.
• If doxycycline was used initially there is a need to be aware that there are tetracycline-resistant forms of U. urealyticum and an alternative may need to be tried, e.g. metronidazole or erythromycin.
• If there is no laboratory evidence of infection then advise no sexual intercourse for seven days and until the partner completes treatment.
• If symptoms continue for >3 months consider the possibility of complications, e.g. prostatitis, epididymitis.
• If there is persistent or recurrent nongonococcal urethritis (NGU) treat with erythromycin or metronidazole.

• Epididymitis and/or orchitis
• Prostatitis
• Systemic dissemination of gonorrhoea, e.g. conjunctivitis, skin lesions
• Reactive arthritis
• Pelvic inflammatory disease (PID) - infection of female partners with the organisms that cause urethritis can cause PID and subsequent complications
• Reiter's syndrome
• HIV transmission increased

If nongonococcal urethritis (NGU), chlamydia and gonorrhoea remain untreated they may rarely remit spontaneously. However, this may take several months and carries the risk of transmission to others if the patient continues to have unprotected sexual intercourse.

1. Management of non-gonococcal urethritis, British Association for Sexual Health & HIV (2007)
2. Urethritis - male, Clinical Knowledge Summaries (September 2009)
3. Management of gonorrhoea in adults, British Association for Sexual Health & HIV (2005)
4. Richens J; Main presentations of sexually transmitted infections in men. BMJ. 2004 May 22;328(7450):1251-3.
5. Miller KE; Diagnosis and treatment of Chlamydia trachomatis infection. Am Fam Physician. 2006 Apr 15;73(8):1411-6. [abstract]
6. Management of Chlamydia trachomatis genital tract infection, British Association for Sexual Health & HIV (2006)
7. Iser P, Read TH, Tabrizi S, et al; Symptoms of non-gonococcal urethritis in heterosexual men: a case control study. Sex Transm Infect. 2005 Apr;81(2):163-5. [abstract]
8. Cassell JA, Mercer CH, Sutcliffe L, et al; Trends in sexually transmitted infections in general practice 1990-2000: population based study using data from the UK general practice research database. BMJ. 2006 Feb 11;332(7537):332-4. Epub 2006 Jan 26. [abstract]
9. Nusbaum MR, Wallace RR, Slatt LM, et al; Sexually transmitted infections and increased risk of co-infection with human immunodeficiency virus. J Am Osteopath Assoc. 2004 Dec;104(12):527-35. [abstract]
10. Guidelines on the Management of Urinary and Male Genital Tract Infections, European Association of Urology (2008)