Urethral Syndrome: Symptoms, Risk factors & Treatment

It is essential to diagnose lower urinary tract symptoms in men and women. If you’re a woman, urinary symptoms will probably translate into a urinary infection.

If you’re a man, the most likely scenario is a prostate condition, usually benign prostatic hyperplasia (BPH).

But what if your doctor tells you that neither of them is causing problems? When that happens, urethral syndrome is another possibility.

But urethral syndrome is not the most common, and you won’t find as much information out there. What is it? How does it feel? How do we diagnose it? In this article, we’re answering these and many other questions about urethral syndrome.

What is urethral syndrome?

In medicine, a syndrome is a set of signs and symptoms usually attributed to a subset of causes. Urethral syndrome is a medical condition with urinary symptoms such as dysuria and urinary frequency. But instead of having prostatitis, BPH, or urinary infections, these patients have no traceable abnormality.

According to the International Continence Society, it should be called Urethral Pain Syndrome instead. However, doctors and patients still know it as a urethral syndrome (1).

One of the most critical aspects of this syndrome is a complete absence of urinary infections. But patients have the same symptoms as urinary infection, with increased frequency and pain. This syndrome may be more common than we’d expect, and around one-quarter of urinary symptoms are due to urethral syndrome.

Urethral syndrome is mostly diagnosed in women. The typical age for the diagnosis is after 30 years and before 50 years. They do not have any vaginal discharge or signs of infection. If they are males, they won’t have prostatitis or BPH. Thus, this is what we know as a diagnosis of exclusion. In other words, it is considered when everything else has been ruled out. That’s why the diagnosis is sometimes controversial, and there’s a lack of consensus in what to do and how (1).

Since we don’t know exactly what it is and its causes, treatment is often complicated. Doctors usually need to start a trial-and-error treatment until one of them improves the symptoms.

What are the symptoms?

As with any other syndrome, the urethral syndrome needs to consider a few major and minor symptoms to be diagnosed. Significant symptoms are the most common. Minor symptoms are in some patients, but not all.

The most common symptoms include (2,3):

  • Dysuria: It is a burning sensation while urinating. This is due to irritation of the urethra or urethral stricture.

  • Increased urinary frequency: Similar to a urinary infection, patients need to urinate more often.

  • Suprapubic pain or discomfort: Pain is often in this area or the low abdominal area. This pain is partially relieved after voiding.

Besides, patients can report many other symptoms. Most of them suggest urinary tract infections, except that it is not due to a bacterial agent. They are (2,3):

  • Difficulty to start urinating: This is particularly common in cases of urethral spasm or stricture. Not all patients will have this obstructive symptom.

  • Slow urinary stream: In males, it will likely be confused with a case of BPH. Since this is a diagnosis by exclusion, doctors suspect it in patients with this type of symptoms and no prostate enlargement. 

  • Incomplete voiding: There’s a sensation of incomplete voiding. In other words, after urinating, you feel you are not finished.

  • Lower back, abdominal, or genital pain: Pain is not always located on the suprapubic or low abdominal area. In some cases, it will be genital pain, particularly on the anterior wall of the vagina. In other cases, pain is in the lower back.

What causes urethral syndrome?

The cause of the urethral syndrome is actually unknown. In the past, it was thought that urethral syndrome was caused by urethral stenosis. While it does explain some cases, it is not the case for many others.

Actually, a very small minority of patients display urethral syndrome symptoms due to urethral stenosis. That’s why current protocols avoid urethral dilation as a ubiquitous procedure for all patients.

Now that we ruled out urethral stenosis as the leading cause of the urethral syndrome, we’re left out with no final answer. No cause has replaced what doctors initially thought to be the trigger of these symptoms. However, a few mechanisms have been proposed (2):

Low-grade infection

Some authors have found a very low-grade bacterial infection in patients with the urethral syndrome. In other words, there is a bacterial infection, but it is so mild that it won’t be positive in urine tests. If this is the case, lowering the threshold to measure bacteriuria can solve the problem. They would be no more than false-negative cases of urinary infections. Still, it is unlikely that this will be the case because these patients do not have leukocytes in the urine. Thus, a complete inflammatory response that usually triggers urinary symptoms is absent.

Inflammation in Skene’s glands

These glands are regarded for some as the female prostate. Some female patients with urethral syndrome have an inflammatory reaction in their Skene gland ducts. They sometimes form a small diverticulum. These could be the reason for their perceived tenderness in the anterior wall of the vagina.

Spasms of the urethral sphincter

Similar to urethral stricture, a spasm of the urethra might be causing the symptoms. In some cases, there’s incomplete relaxation of the smooth muscle. The patient has urinary retention and different degrees of urinary symptoms. These cases may improve with alpha-blockers or urethral dilation procedures.

Bladder pain syndrome and interstitial cystitis

According to some authors, the urethral syndrome can be a case of interstitial cystitis or painful bladder syndrome. If this is the case, it would be a very mild case of interstitial cystitis. This postulate is sometimes considered because certain tests are positive in both diseases. For example, the potassium sensitivity test. However, this only shows an increase in epithelial leakiness. Plus, interstitial cystitis is only a bladder problem. However, these patients feel tenderness in the distal part of the urethra. Thus, we can’t explain all cases by this mechanism or postulate.

Psychogenic disease

Some studies have evaluated the relationship between the urethral syndrome and a psychological component. These patients have a higher risk of diagnoses such as hysteria, hypochondriasis, or schizophrenia. They are usually apprehensive about any symptom. They may also have difficulty recognizing their emotional states. Thus, they bring their psychological afflictions to the body. However, anxiolytics do not cure the disease. Therefore, labeling all of these patients as hypochondriacs is just not right.

Hormonal problems

The bladder is affected by estrogen because it comes from the same origin as the female genitals. Thus, a fluctuation of estrogen may lead to transient urinary symptoms due to urethral syndrome. More specifically, a reduction in estrogen levels may be the culprit. That’s why many postmenopausal patients with this syndrome benefit so much from estrogen therapy.

There is not a single cause. Similar to other multifactorial diseases, the urethral syndrome is more likely due to an interplay of factors. Each one has a role and should be considered to treat patients.

Risk factors

The cause of the urethral syndrome is not clear, but we can measure when it is more common. Risk factors increase your chance of experiencing this ailment and include (3):

  • Past kidney or bladder infections. After infection, and even if you’re completely cured, the urethra is still sensitive. Thus, it can trigger pain and other symptoms with a negative urine culture.

  • Patients with a narrow urethra, as in urethral stricture.

  • Patients under immunosuppressant medications.

  • Unprotected sex. This increases the chance of sexually-transmitted diseases. They represent a very important risk factor for this disease.

  • Patients with sexually-transmitted diseases. More specifically, they include chlamydia, gonorrhea, or mycoplasma genitalium. They all increase the risk of urethral syndrome.

  • Young patients living an active sexual life. They have an increased chance of sexually-transmitted diseases.

  • Eating foods that irritate the urethral lining. For example, foods or beverages with caffeine, spicy food, and alcohol.

  • Contact with urethral irritants. For example, scented soaps, douches, and some sanitary products. They may contain chemicals that trigger irritation in the urethra.

Diagnosis

Urethral syndrome is a diagnosis of exclusion. It means that doctors only consider it when they have ruled out other causes. One of the most critical factors for the diagnose is considering the medical records. A history of dysuria, urinary frequency, and suprapubic pain suggests urinary infections or urethral syndrome. 

It is essential to differentiate nocturia with increased urinary frequency. These patients do not wake up several times at night to urinate. But they need to use the bathroom every 30 to 60 minutes. The pain is not severe and does not disturb the patient’s sleep (4).

Different questionnaires evaluate this type of symptoms, including the Urogenital Distress Inventory, the International Consultation on Incontinence Questionnaire of Female Lower Urinary Tract Syndrome, and the International Prostate Symptom Score in males.

A physical examination is also crucial for the diagnosis. It is often performed once again after ruling out other diagnoses. But even the first time, it is useful to rule out vaginitis, herpes, and other infections. In some cases, patients have atrophic vaginitis, atrophic urethritis, or a cystocele. But the rest is often unremarkable.

What doctors rule out

This is what doctors rule out to ultimately reach the diagnosis of the urethral syndrome:

  • Urinary infections, particularly in women but also in men. We rule this out with urinalysis and urine cultures.

  • Benign prostatic hyperplasia and other prostate conditions, especially in aging men. They often use a combination of diagnostic imaging, digital rectal examination, and PSA tests to detect it.

  • Prostatitis in younger males, depending on their symptoms. It is evaluated via imaging tests and physical examination.

  • Herpes zoster and other sexually-transmitted diseases. It is ruled out because of its cutaneous manifestations or a swab test.

  • Neurologic conditions, usually associated with hypersensitivity. Thus, it is essential to evaluate sensitivity in different areas of the body.

  • Squamous cell carcinoma or condyloma, which look like white or reddish patches in the skin

  • Urethral prolapse, which is also noticeable in a physical exam.

  • Urethral atrophy, usually suggested by thin, pale, and dry mucosa.

  • A urethral diverticulum, cystocele, rectocele, or urethrocele. They are diagnosed with different pressure maneuvers in the physical exam.

  • Cervicitis and foreign bodies such as retained tampons. This causes inflammation and triggers urinary symptoms.

  • Interstitial cystitis (bladder pain syndrome) which features severe pain instead of mild or moderate discomfort.

  • Side effects of radiation therapy in patients undergoing cancer treatment

  • Spinal cord lesions and other nerve diseases.

Diagnostic tests

  • A urinalysis, which only has up to 3 red blood cells per field and doesn’t have elevated glucose levels. Bacterial colony count should be 100/mL or less.

  • A pap smear, especially to rule out cervical malignancy.

  • A pregnancy test in case of irregular menstrual cycles.

  • Vaginal swabs to rule out a sexually-transmitted infection

  • A kidney and bladder ultrasound to visualize the organs and rule out masses and other diagnoses

  • Cystography in patients with a possible urethral diverticulum

  • A complete urodynamic evaluation to evaluate bladder function.

  • Cystourethroscopy in patients who are suspicious of interstitial cystitis

  • Bladder biopsy when patients are suspicious of bladder cancer or urethral cancer.

A combination of diagnostic tools can be used depending on each patient.

Treatment options

Treatment for urethral syndrome follows a trial-and-error basis. There is not a single treatment protocol. Instead, doctors try a combination of medical care and sometimes surgical solutions.

Medical care includes certain medications, including hormone replacement therapy in postmenopausal women, alpha-blockers in cases of urethral spasms, antibiotics when they suspect false-negative infections, and local corticosteroids when there’s severe inflammation. Other medications include muscle relaxants, tricyclic antidepressants, and anesthetics (6).

Recent studies suggest that biofeedback and behavioral therapy may also have a role in the treatment. They are particularly useful when the problem is a failure to relax pelvic muscles while voiding (7).

Doctors mainly recommend surgical care in known cases of urethral stricture or an implantable system that stimulates the sacral nerve to favor voiding.

Prevention tips

After considering risk factors, we can also find several prevention tips. For example:

  • Avoid unprotected sex, especially penetrative anal intercourse without a condom in males.

  • Check for sexually-transmitted diseases

  • Avoid spicy food, caffeine, and alcohol

  • Evaluate your hygiene products, especially if you recently bought them and started experiencing symptoms. Try to use natural products and avoid scented soaps and cosmetics.

Conclusion

The urethral syndrome is suspected in patients with UTI symptoms or urethral pain without bacteriuria or a large prostate gland. It can be an acute urethral syndrome when the symptoms recently appeared or a chronic urethral syndrome when they are constant or coming back every now and then.

The symptoms include suprapubic pain, painful urination, and increased urinary frequency. Other symptoms include a reduced urinary flow and other symptoms of urethral obstruction. There are multiple causes, including spasms in the urethral sphincter, irritation of the urethra, or an overactive bladder. As noted, these are mainly urinary symptoms and may include urinary incontinence.

Urethral syndrome is a diagnosis of exclusion. In other words, doctors need to rule out other causes first. For example, it is very important to rule out chronic UTI, especially in female patients with frequent urinary tract infections. BPH should also be excluded in males as a cause of lower urinary tract symptoms.

After a careful physical exam and ruling out many diseases, doctors can finally diagnose urethral syndrome. Treatment is also challenging because there is no consensus about where to start and what to do. Healthcare providers consider different treatments on a trial-and-error basis until there’s a symptomatic improvement.

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Sources

  1. van Kerrebroeck, P., Victor, A., & Wein, A. (2002). The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourology and urodynamics, 21, 167-178.
  2. Phillip, H., Okewole, I., & Chilaka, V. (2014). Enigma of urethral pain syndrome: why are there so many ascribed etiologies and therapeutic approaches?. International Journal of Urology, 21(6), 544-548.
  3. Gürel, H., Gürel, S. A., & Atilla, M. K. (1999). Urethral syndrome and associated risk factors related to obstetrics and gynecology. European Journal of Obstetrics & Gynecology and Reproductive Biology, 83(1), 5-7.
  4. Xixin, W. U. (2001). Clinical analysis of urethral syndrome and literature review. Clinical Medicine of China, (07).
  5. Tyagi, P., Moon, C. H., Janicki, J., Kaufman, J., Chancellor, M., Yoshimura, N., & Chermansky, C. (2018). Recent advances in imaging and understanding interstitial cystitis. F1000Research, 7.
  6. Costantini, E., Zucchi, A., Del Zingaro, M., & Mearini, L. (2006). Treatment of urethral syndrome: a prospective randomized study with Nd: YAG laser. Urologia internationalis, 76(2), 134-138.
  7. Yu, H. S., Lee, T., Suh, J. K., Kang, Y. S., & Son, I. C. (2000). The Biofeedback therapy in Female Urethral Syndrome. Journal of the Korean Continence Society, 4(2), 85-90

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