Nongonococcal Urethritis: Symptoms, Types, Causes and Treatment

Nongonococcal urethritis (NGU) is a common and often misunderstood condition affecting the urethra, primarily in men. Unlike gonococcal urethritis, which is caused by the bacterium Neisseria gonorrhoeae, NGU encompasses a wide range of infectious and non-infectious etiologies. Understanding its symptoms, types, causes, and treatment options is crucial for prompt diagnosis, effective therapy, and prevention of complications for both patients and their partners. In this article, we’ll delve into the most up-to-date evidence on NGU, drawing from leading clinical and research sources.

Symptoms of Nongonococcal Urethritis

Nongonococcal urethritis can present in subtle or obvious ways, sometimes making it tricky to distinguish from other urinary tract or genital conditions. Recognizing the key symptoms is vital for early detection and treatment.

Symptom	Frequency/Description	Distinctiveness	Source(s)
Dysuria	Pain or burning on urination	Very common, variable	1 2 3 5
Discharge	Mucoid or watery, often mild	Not always present; may require penile stripping	1 2 3 5 7
Itching/Tingling	Sensation in urethra or penis	May be subtle	2 5
Duration	Often longer than gonococcal urethritis	Lasts days to weeks	1 3

Table 1: Key Symptoms of Nongonococcal Urethritis

Recognizing the Symptoms

NGU typically manifests as dysuria—a burning or stinging sensation during urination. This is the most common complaint and often prompts men to seek care. However, unlike gonorrhea, which produces a prominent, purulent discharge, NGU discharge is usually milder, mucoid, or even absent. In many cases, discharge can only be elicited by “stripping” the urethra or may go unnoticed entirely 1 3.

Other symptoms include:

• Penile itching or tingling, which may be subtle or mistaken for irritation 2.
• Mild redness at the urethral opening.
• Less commonly, mild swelling or discomfort in the penis.

Duration and Variability

One distinctive aspect of NGU is the variable and often prolonged duration of symptoms. While gonococcal urethritis tends to present acutely and dramatically, NGU may develop gradually and linger for weeks if not treated 1 3.

Less Common and Overlapping Symptoms

Some men may experience urinary frequency, urgency, or even low-grade discomfort in the pelvic area. In cases where the prostate is involved, mild tenderness or enlargement may be detected on examination 3. Notably, symptoms can overlap with other urogenital conditions, making clinical examination and laboratory testing essential for accurate diagnosis 2.

Types of Nongonococcal Urethritis

While NGU is often discussed as a single entity, it actually encompasses several distinct subtypes, each with unique features and implications for treatment.

Type	Main Features	Common Pathogens/Associations	Source(s)
Chlamydial NGU	Most common, often subacute	Chlamydia trachomatis	2 3 4 6 7 9
Mycoplasma NGU	Mild or persistent symptoms	Mycoplasma genitalium	6 7 12 14 15
Ureaplasma NGU	Chronic/relapsing, subtle signs	Ureaplasma urealyticum	3 6 7 9 10
Trichomonas NGU	Variable severity, sometimes asymptomatic	Trichomonas vaginalis	6 7 11 15
Viral NGU	May have systemic or local symptoms	HSV, adenovirus	6 7
Idiopathic NGU	No identified pathogen	? (possible novel bacteria)	7 13

Table 2: Types of Nongonococcal Urethritis

Chlamydial NGU

The most common cause of NGU is Chlamydia trachomatis. Chlamydial urethritis often presents with mild discharge and dysuria and can be easily missed due to its subtlety. It can also lead to complications if untreated, such as epididymitis or transmission to sexual partners 2 3 4 7.

Mycoplasma and Ureaplasma NGU

Newer research has highlighted Mycoplasma genitalium as a significant, sometimes overlooked, cause of NGU. This organism is often implicated in persistent or recurrent cases, especially if initial treatment fails 6 7 12. Ureaplasma urealyticum is another frequent cause, leading to chronic or relapsing symptoms and sometimes showing resistance to standard therapies 3 6 7 10.

Trichomonas and Viral NGU

Trichomonas vaginalis can cause NGU, particularly in regions with high prevalence, but is less common in the West. It can be asymptomatic or cause mild symptoms 6 7 11 15. Viruses like herpes simplex virus (HSV) and adenoviruses are recognized causes, leading to urethritis with or without typical genital lesions, and are associated with orogenital exposure 6 7.

Idiopathic NGU

In up to 45% of cases, no organism is identified despite thorough testing. Recent studies suggest that newly described bacteria, such as Leptotrichia/Sneathia spp. and other bacterial vaginosis-associated bacteria, may play a role in some of these “idiopathic” cases 7 13. Idiopathic NGU often occurs in older men and is less likely to be linked to high-risk sexual behavior 7.

Causes of Nongonococcal Urethritis

Understanding the causes of NGU is key to targeted treatment and prevention. The spectrum stretches from well-established sexually transmitted pathogens to emerging, less-understood bacteria, and even non-infectious triggers.

Cause/Agent	Prevalence/Significance	Notes/Resistance Issues	Source(s)
Chlamydia trachomatis	20–43% of NGU cases	Leading cause; treatable	3 4 6 7 9 15 17
Mycoplasma genitalium	9–31% of NGU cases	Linked to persistent NGU, rising resistance	6 7 12 14 15 16
Ureaplasma urealyticum	15–60% (varies by region, study)	Chronic/persistent forms	3 6 7 9 10 16 17
Trichomonas vaginalis	2–20% (higher in some populations)	Often missed without DNA testing	6 7 11 15
Viruses (HSV, Adenovirus)	2–6%	Orogenital transmission	6 7
Emerging BV-Associated Bacteria	5–15%	Leptotrichia/Sneathia, etc.	13
Non-infectious/Other	Rare	Trauma, chemicals, diet	8
Unknown (Idiopathic)	Up to 45%	Possibly new pathogens	7 13

Table 3: Causes of Nongonococcal Urethritis

Sexually Transmitted Pathogens

• Chlamydia trachomatis remains the single most important cause of NGU, especially among young, sexually active men 2 3 4 15 17.
• Mycoplasma genitalium is increasingly recognized as a significant pathogen, especially in cases that do not resolve with standard chlamydia treatment 6 7 12 14 15 16.
• Ureaplasma urealyticum is frequently detected, with some studies suggesting it may explain a substantial proportion of chlamydia-negative NGU 3 6 7 9 10 16 17.
• Trichomonas vaginalis is an important but often underdiagnosed cause. Its prevalence varies by region, and DNA-based diagnostics are making detection more common 6 7 11 15.
• Viral causes include HSV and adenoviruses, particularly in men with orogenital exposures 6 7.

Novel and Emerging Bacteria

Recent studies have identified bacterial vaginosis-associated bacteria—notably Leptotrichia/Sneathia spp.—as possible contributors to idiopathic NGU. These bacteria often coexist with others and may be part of a pathogenic microbiota 13.

Non-Infectious Triggers

NGU can also result from non-infectious causes, including:

• Mechanical trauma (e.g., instrumentation, vigorous sexual activity)
• Chemical irritation (e.g., soaps, spermicides, certain foods or drugs)
• Inflammation secondary to systemic disease

However, these are rare compared to infectious causes 8.

The Role of Coinfection and Persistent/Recurrent NGU

Coinfection with multiple organisms is possible and may complicate diagnosis and management. Persistent or recurrent NGU is common, especially when a causative agent cannot be isolated, leading to repeated courses of antibiotics and diagnostic frustration 4 18. Resistance, especially among Mycoplasma genitalium and Ureaplasma, is an emerging issue 14 16.

Treatment of Nongonococcal Urethritis

Effective management of NGU aims to relieve symptoms, eradicate pathogens, prevent complications, and limit transmission to sexual partners. Recent changes in resistance patterns and the emergence of new pathogens have informed updated treatment strategies.

Regimen	Typical Dosage	Efficacy/Notes	Source(s)
Azithromycin	1 g single dose (oral)	Similar efficacy to doxycycline; rising resistance in MG	9 12 14 15 16 17
Doxycycline	100 mg twice daily × 7 days	Equally effective; may be superior for Chlamydia	3 9 13 15 16 17
Tinidazole	2 g single dose (oral)	Used for T. vaginalis; added for broader coverage	15
Minocycline	100 mg 1–2× daily × 7–21 days	Longer duration may delay recurrence	18
Other options	Erythromycin, fluoroquinolones	For special cases or resistance	12 15
Partner therapy	Empiric treatment for partners	Essential for preventing reinfection	2

Table 4: Common Treatments for Nongonococcal Urethritis

First-Line Treatments

The mainstays of empirical therapy are a single dose of azithromycin or a 7-day course of doxycycline, both of which offer similar overall cure rates (approximately 75–81%) 9 16 17. Clinical guidelines recommend these regimens due to their ease of use and coverage of the most common pathogens. However, studies show that doxycycline may be more effective for chlamydial NGU, while azithromycin has been preferred for its single-dose convenience 15 17.

Addressing Resistance and Special Pathogens

• Mycoplasma genitalium: Treatment failure with azithromycin is increasingly reported, linked to induced macrolide resistance. In such cases, moxifloxacin or other fluoroquinolones may be required, but resistance is also emerging 12 14 16.
• Trichomonas vaginalis: If trichomonas is detected or strongly suspected, adding tinidazole or metronidazole is necessary, as neither azithromycin nor doxycycline is effective against this protozoan 15.
• Persistent NGU: If symptoms recur, it is essential to reassess for alternative or resistant pathogens and consider extended or alternative antibiotic regimens. In some idiopathic cases, doxycycline may outperform azithromycin for certain BV-associated bacteria 13.
• Minocycline: Longer courses (21 days) may delay but not prevent recurrence, especially in cases where no pathogen is detected 18.

Partner Notification and Treatment

Treating sexual partners is critical to prevent reinfection and curb ongoing transmission. Expedited partner therapy (EPT), where prescriptions are provided for partners without formal evaluation, is endorsed by major guidelines 2.

Monitoring and Prevention of Complications

• Follow-up testing is recommended, especially if symptoms persist.
• HIV and other STI screening should be considered, given the overlapping risk factors and increased HIV shedding during active urethritis 2.

Conclusion

Nongonococcal urethritis is a diverse, evolving clinical syndrome that demands a nuanced, evidence-based approach. Here’s what we’ve learned:

• NGU symptoms are often mild and variable, centering on dysuria and sometimes subtle discharge.
• Multiple types of NGU exist, with Chlamydia trachomatis, Mycoplasma genitalium, and Ureaplasma urealyticum as key pathogens.
• Causes include both established and newly emerging infectious agents; up to 45% of cases remain idiopathic, but novel bacteria are increasingly implicated.
• Treatment relies on azithromycin or doxycycline, but resistance, particularly among Mycoplasma genitalium, is a growing concern.
• Partner treatment and prevention of complications are essential for comprehensive care.

Key Points:

• Recognize and promptly treat symptoms of NGU to prevent complications.
• Be aware of new and resistant pathogens—consider tailored therapy if standard regimens fail.
• Always ensure sexual partners are treated to break the cycle of reinfection.
• Ongoing surveillance for emerging causes and resistance patterns is vital for future management.

Understanding NGU means staying alert to its evolving landscape—keeping up with the science is the first step to better outcomes for patients and communities.