Prostatitis

Author: Dr Anthony J. Schaeffer University of Chicago 2008-07-28

Introduction

 Prostatitis is a common, frequently inflammatory disorder of the prostate, affecting approximately 5% of men in the United States and associated with considerable quality of life and financial impact. This term is used to describe three distinct clinical conditions (Table 1):

1. An acute or chronic bacterial infectious disease
2. A non-infectious pain syndrome (known as Chronic Pelvic Pain Syndrome or CPPS) 
3. An asymptomatic inflammatory disease   

About 10% of men with symptoms of prostatitis have an acute or chronic bacterial infection that is diagnosed by well-defined clinical and laboratory characteristics and usually responds to appropriate antimicrobial therapy.

The majority of men with symptoms of prostatitis have a chronic pelvic pain syndrome (CPPS) that may also be associated with difficult or irritative urination. Symptoms may wax and wane in intensity, but usually persist over time; the reduction in the patient’s quality of life can be severe and is similar to that associated with other chronic conditions such as heart failure, inflammatory bowel disease, and diabetes mellitus.

Asymptomatic inflammatory prostatitis is an incidental finding of inflammation in expressed prostatic fluid during evaluation for elevated serum prostate-specific antigen (PSA) levels or infertility, and will not be discussed here.

What Causes Prostatitis? 

The prostate is a gland within the male reproductive system located directly beneath the bladder. Small and walnut-shaped, it measures approximately one and a half inches in length and is surrounded by pelvic muscles. Encircling the urethra (the conduit that carries both urine and seminal fluids from the body), the prostate is responsible for producing a protein that is part of a man’s semen; during ejaculation, muscles in the prostate contract to push the prostatic fluid through tiny ducts into the urethra where it mixes with sperm and other fluid prior to exiting the body. Infectious prostatitis, also known as bacterial prostatitis, is caused by factors associated with urinary tract infections. These include obstruction of urinary flow, urinary retention, and passage of instruments into the urinary tract. The bacteria that cause prostatitis usually migrate from the bacterial flora of the colon, presumably either by direct transfer into the prostate or by ascending up the urethra. The most common cause of infectious prostatitis is the gram-negative bacteria Escherichia coli (E. coli) which is responsible for about 80% of all urinary tract infections. Other gram-negative bacteria and gram-positive enterococci account for the remainder of infections. If the infection is caused by instrumentation of the urinary tract, such as passage of a catheter, more aggressive organisms such as Pseudomonas aeruginosa can be causative. Other agents, such as yeast, viruses, and sexually transmitted organisms, do not cause infectious prostatitis.

The cause of CPPS is unknown, but has been linked to a variety of conditions such as voiding dysfunction, auto-immunity, inflammatory mediators, and psychologic disturbance, but the connection between these conditions and CPPS is not clear.

When Should Prostatitis Be Suspected? 

Infectious acute bacterial prostatitis (ABP) is a life-threatening systemic infection associated with acute febrile urinary tract infection and physical exam revealing a warm, tender prostate. A urinalysis showing evidence of infection (i.e. - inflammatory cells and bacteria) and subsequent positive urine culture confirms the diagnosis.

Infectious chronic bacterial prostatitis (CBP) should be suspected in men with symptoms of recurrent lower urinary tract infection bracketed by relatively asymptomatic periods. If urine cultures obtained during symptomatic episodes show urinary tract infection caused by the same strain of bacteria, chronic bacterial prostatitis should be considered.

Many patients present with a history of recurring pain and irritative symptoms suggestive of urinary tract infection that have been treated empirically without culture documentation. Therefore, in these cases, the first step is to obtain urine cultures during symptomatic episodes to document the presence or absence of bacteriuria.

Non-infectious prostatitis/Chronic Pelvic Pain (CPPS) is a syndrome based on the patient’s symptoms of pain in the pelvic region with or without obstructive or irritative voiding symptoms. Since the symptoms may mimic an infectious event, a urine culture is required to demonstrate that infection is not present. Since non-infectious prostatitis is a diagnosis of exclusion, it is imperative that other conditions that could mimic symptoms of chronic pelvic pain be ruled out. In addition to infection, these include lower urinary tract obstructive symptoms due to enlargement of the prostate (like benign prostatic hyperplasia [BPH, an enlargement of the prostate gland that occurs commonly as men age] or prostate cancer) or interstitial cystitis. In some instances, specific symptoms such as pain during or after ejaculation, may suggest obstruction of the ejaculatory ducts.

Physical examination is not diagnostic for either chronic bacterial prostatitis or CPPS, but physical examination and urinalysis should be performed to rule out bladder distention, prostate induration, or asymmetry that are associated with benign or malignant prostate disease. Laboratory tests are not helpful and may be misleading. Prostate-specific antigen (PSA), for example, can be arbitrarily elevated due to infection or prostate inflammation (i.e., - category IV). Patients with prostatitis and elevated PSA should be carefully monitored; if the PSA does not become normal after treatment of infection, evaluation for prostate cancer should be undertaken.

How Should Patients with Prostatitis be Evaluated? 

Acute Bacterial Prostatitis

Because of the severity of the condition, steps should be taken to rule out underlying comorbidities that would contribute to and/or exacerbate acute bacterial prostatitis. Laboratory tests for blood counts to rule out diabetes mellitus, and imaging such as computed tomography (CT) scan to rule out functional or anatomical abnormalities of the urinary tract, should be considered.

Chronic Bacterial Prostatitis

In a man with documented urinary tract infections it is possible structural or functional abnormalities of the urinary tract exist. For this reason, urinary tract imaging should be performed; for example, CT scans of the kidneys and pelvis may identify abnormalities such as kidney stones or obstruction of flow from an enlarged prostate that are causing the recurrent urinary tract infections. If these conditions are identified, they should be addressed. If the imaging studies show no evidence of structural or functional abnormalities of the urinary tract, then it is appropriate to determine whether or not the prostate is the source of the bacteria that cause the urinary tract infections. This can not be done when the patient has an active bladder infection, and therefore the patient should be prescribed an antimicrobial agent such as penicillin or nitrofurantoin which will treat the urinary tract infection but not penetrate the prostatic tissue and fluid, thereby temporarily masking the possibility of culturing bacteria residing within the prostate.

When the bladder infection is treated and urine from the bladder shows no bacterial growth, prostate localization cultures (the Meares-Stamey test) should be performed to determine if the prostate is the reservoir of bacteria between episodes of symptomatic bladder infection (Figure 1). One can presume that these bacteria periodically escape and are the cause of recurrent urinary tract infections. The goal is to collect sequential specimens of urine before prostatic massage from the urethra (voided bladder 1 [VB1]) and bladder (voided bladder 2 [VB2]), prostatic fluid during prostate massage (expressed prostatic secretions [EPS]), and urine after massage (voided bladder 3 [VB3]). A simple two-glass test utilizing a midstream urine specimen (VB2) and a post-prostatic massage urine specimen (VB3) compares favorably to the four-glass test. Cultures are performed to quantify the number of bacteria in the specimens. If pathogenic bacteria are found only in the specimens containing prostatic fluid (EPS or VB3), or if the levels in the specimens containing prostatic fluid are at least 10 times the levels found in the urethral urine specimen (VB1), then the patient is judged to have chronic bacterial prostatitis.
 

Chronic Pelvic Pain Syndrome

There are no confirmatory tests for CPPS. The four-glass or two-glass tests may be performed to see if there is any evidence of prostate inflammation. This is done by looking at the expressed prostatic secretions under a microscope and counting the number of white blood cells per high power field. Most healthy men have less than 10 white blood cells per high power field. About 50% of men with chronic pelvic pain syndrome have 10 or more white blood cells per high power field, suggesting that the inflammation may contribute to CPPS. However, the usefulness of the test is questionable because:

• Asymptomatic men with elevated PSA (category IV) and infertile men can have elevated white blood cell levels in expressed prostatic secretion
• Fifty percent of men with CPPS do not have elevated white blood cell count in their expressed prostatic secretion 
• The number of white blood cells in the expressed prostatic secretion does not correlate with pain symptoms

Because CPPS is thought to be non-infectious, one would think that localization cultures would always show no pathogenic bacteria. Surprisingly, however, studies have shown that up to 5% of men with CPPS, and a similar percentage of asymptomatic men, have positive prostatic localization cultures.

These observations can be interpreted in a variety of ways: 1) prostatic inflammation and bacteria (and for that matter, the prostate itself) may have nothing to do with CPPS; 2) in some cases, inflammation and/or bacteria in the prostate may contribute to their chronic pelvic pain; 3) in the absence of inflammation and bacteria, the role of the prostate in CPPS, as well as efforts to empirically treat CPPS with anti-inflammatories and antimicrobials, could be questioned.

If patients with CPPS have significant lower urinary tract symptoms they may benefit from urodynamic studies designed to evaluate bladder function and bladder outlet obstruction. Imaging studies are not indicated for most patients. However, if patients have a specific complaint (such as pain with or following ejaculation), pelvic imaging by CT scan or transrectal ultrasound may reveal dilation of the ejaculatory duct or seminal vesicle, consistent with obstruction and possibly contributing to CPPS. These tests should not be performed on a routine basis.

Treatment 

Acute Bacterial Prostatitis

This serious, potentially life-threatening condition requires immediate and aggressive medical therapy (Table 2.1 and 2.2). Broad spectrum antimicrobial intravenous therapy must be initiated immediately. When the result of the urine culture and bacterial susceptibility are available and the patient has improved, the patient may be switched to an oral regimen. Therapy should be continued for about 14 days. Patients may experience difficulty voiding and require catheter drainage.

If the patient does not respond appropriately, the possibility of a prostatic abscess should be evaluated by a CT scan of the pelvis. A prostatic abscess frequently requires drainage.
   

 Chronic Bacterial Prostatitis

Treatment for chronic bacterial prostatitis requires antimicrobial therapy that is able to:

• Penetrate into the prostatic tissue

• Kill the bacterial pathogen

The best antimicrobial therapy is a fluoroquinolone such as ciprofloxacin or levofloxacin; this should be administered for 28 days (Table 2.3). If the pathogen is E. coli or other agents commonly susceptible to fluoroquinolones, there is an approximate 80% chance of eradicating the bacteria. If the bacteria is a more resistant organism, such Pseudomonas, then success rates are reduced. Once the treatment is deemed successful by negative prostatic localization cultures following therapy, patients should still be monitored for 6-12 months to be sure there are no relapses of infection.

When using an antimicrobial that is effective against the bacteria in the prostate, if the bacteria can not be eliminated and the patient continues to have recurrent urinary tract infections, there are two options:

1. Provide the patient with intermittent antimicrobial therapy to treat symptomatic urinary tract infections.
2. Provide a low dose of suppressive antimicrobial therapy to prevent development of bladder infections.

 

Chronic Pelvic Pain Syndrome

There is no effective treatment for CPPS. Since its cause is unknown, treatment tends to focus on relief of pain or voiding symptoms rather than elimination of the underlying problem. The fact that there may be multiple factors involved in the cause of chronic pain makes therapy even more difficult (Table 2.4).
 

Before initiating any therapy, the severity of the patient’s symptoms should be quantified using the NIH Chronic Prostatitis Symptom Index (see “More Resources” below for an online link). This is a nine-item, self-administered test that is reliable, valid, and available in many languages. The test can be used to assess the patient’s base-line status so their response to therapy can be objectively assessed. The completed questionnaire will score between 0 and 43; a score of 15 or more is judged to be consistent with moderate symptoms, with higher scores indicating more severe symptoms. A reduction of four to six points is compatible with clinically relevant and successful therapy. Since the causes of CPPS are poorly understood, may be multiple and not linked to any biomarkers, therapy is challenging and empiric (Table 3).

Alpha-Blockers

These drugs are designed to reduce the smooth-muscle tension in the prostatic urethra, thus improving flow of urine and presumably reducing pain associated with CPPS. Randomized controlled studies in patients with moderate to severe symptoms of short duration have shown statistical improvement when therapy has been administered for 12-14 weeks [1, 2, 3, 4, 5]. The duration of pre-existing symptoms does not appear to influence the success, but prior exposure to the therapy diminishes effectiveness. Results have been best in trials involving longer duration of therapy (up to 3 months or longer). The side effects include dizziness, fatigue, drop in blood pressure, and decrease in ejaculate volume.

Antimicrobial Therapy

Randomized, controlled trials have shown no benefit from antimicrobial therapy for CPPS. However, these trials utilized patients with long duration of symptoms, and many patients had received antimicrobial therapy in the past [5, 6]. Thus, it is possible that some of the chronic pelvic pain patients with bacteria in the prostatic secretions could benefit from antimicrobial therapy.

Other Therapies for Chronic Pelvic Pain

The following therapies have some proven benefit in small placebo-controlled trials, but confirmation in larger studies is lacking:

• Quercetin: a bioflavonoid that acts as an antioxidant and is available over the counter [7]

• Mepartricin: a drug that works to lower the concentration of estrogen plasmatic levels in the prostate [8]

• Transurethral microwave thermotherapy: an interventional therapy to heat the prostate [7]

• Physical therapy/biofeedback [9, 10]

• Acupuncture [11]

The following drugs have no demonstrated benefit for treating chronic pelvic pain:

• Pentosan polysulfate [12]

• Rofecoxib [13]

• Muscle relaxants

• Bee-pollen extract

• Saw palmetto

• Corticosteroids

• Allopurinol

Physical therapy utilizing pelvic massage and sitz baths may be useful for patients with chronic pelvic pain, but controlled trials demonstrating any benefit are lacking.

 Guidelines

There are no issued guidelines for the management of chronic bacterial prostatitis or CPPS.

Recommendations

ABP/CBP : antimicrobial therapy based on culture/microbiologic response is recommended for the management of acute and chronic bacterial prostatitis.

CPPS : Goal-directed therapy is recommended for CPPS. Initial therapy should be a minimum 12-week course of an alpha-blocker which can be continued if a good response is observed[14]. If the patient does not respond, empiric therapy can be utilized and efficacy based on changes in the NIH-CPSI.

Conclusions 

Prostatitis has many definitions and patients require careful assessment and testing to reach the correct diagnosis.

In the presence of recurrent urinary tract infections with the same bacterial strain, CBP is likely; in the absence of recurrent urinary tract infections, CPPS is likely.

Infectious prostatitis, although uncommon, usually responds to appropriate antimicrobial therapy.

Non-infectious prostatitis is associated with significant morbidity and treatment is frustrated by a lack of many effective agents. Outcomes-based empiric therapy should be provided to individuals with the intent to reduce, if not eliminate, their symptoms.

Men with persistent lower urinary tract obstructive or irritative symptoms, despite empiric therapy, should be offered urologic referral. They may have bladder pathology or bladder outlet obstruction that could benefit from medical or surgical urologic intervention.

More Information 

Web Resources  

The Prostatitis Foundation (www.prostatitis.org)

All About Prostate (www.allaboutprostate.com)

National Kidney and Urologic Diseases Clearinghouse (http://kidney.niddk.nih.gov/kudiseases/pubs/prostatitis/)

NIDDK-NIH Home Page - search “prostatitis index” for a copy of the test online ( http://www2.niddk.nih.gov/)

Books about Prostatitis   

David Wise, A Headache in the Pelvis: A New Understanding and Treatment for Prostatitis and Chronic Pelvic Pain Syndromes, 4th Edition.

Bradley Hennenfent, The Prostatitis Syndromes: Approaches to Treating Bacterial Prostatitis, Non-Bacterial Prostatitis, Prostatodynia, Benign Prostatic Hyperplasia, Sexual Dysfunction, Bashful Bladder Syndrome, Waking at Night to Urinate, and Possibly Preventing Prostate Cancer.

Peter Scardino and Judith Kelman, Dr. Peter Scardino’s Prostate Book: The Complete Guide to Overcoming Prostate Cancer, Prostatitis, and BPH.

J. Curtis Nickel, The Prostatitis Manual: A Practical Guide to Management of Prostatitis/Chronic Pelvic Pain Syndrome.

Icon Health Publications, The Official Patient’s Sourcebook on Prostatitis: A Revised and Updated Directory for the Internet Age.

References

1. Cheah PY, Liong ML, Yuen KH, et al. Terazosin therapy for chronic prostatitis/chronic pelvic pain syndrome: a randomized, placebo controlled trial. J Urol 2003;169(2):592-6.
2. Mehik A, Alas P, Nickel JC, Sarpola A, Helstrom PJ. Alfuzosin treatment for chronic prostatitis/chronic pelvic pain syndrome: a prospective, randomized, double-blind, placebo-controlled, pilot study. Urology 2003;62(3):425-9.
3. Evliyaoglu Y, Burgut R. Lower urinary tract symptoms, pain and quality of life assessment in chronic non-bacterial prostatitis patients treated with alpha-blocking agent doxazosin; versus placebo. Int Urol Nephrol 2002;34(3):351-6.
4. Nickel JC, Narayan P, McKay J, Doyle C. Treatment of chronic prostatitis/chronic pelvic pain syndrome with tamsulosin: a randomized double blind trial. J Urol 2004;171(4):1594-7.
5. Alexander RB, Propert KJ, Schaeffer AJ, et al. Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome: a randomized, double-blind trial. Ann Intern Med 2004;141(8):581-9.
6. Nickel JC, Downey J, Clark J, et al. Levofloxacin for chronic prostatitis/chronic pelvic pain syndrome in men: a randomized placebo-controlled multicenter trial. Urology 2003;62(4):614-7.
7. McNaughton Collins M, MacDonald R, Wilt TJ. Diagnosis and treatment of chronic abacterial prostatitis: a systematic review. Ann Intern Med 2000;133(5):367-81.
8. De Rose AF, Gallo F, Giglio M, Carmignani G. Role of mepartricin in category III chronic nonbacterial prostatitis/chronic pelvic pain syndrome: a randomized prospective placebo-controlled trial. Urology 2004;63(1):13-6.
9. Nadler RB. Bladder training biofeedback and pelvic floor myalgia. Urology 2002;60(6 Suppl):42-3; discussion 4.
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11. Chen R, Nickel JC. Acupuncture ameliorates symptoms in men with chronic prostatitis/chronic pelvic pain syndrome. Urology 2003;61(6):1156-9; discussion 9.
12. Nickel JC, Forrest JB, Tomera K, et al. Pentosan polysulfate sodium therapy for men with chronic pelvic pain syndrome: a multicenter, randomized, placebo controlled study. J Urol 2005;173(4):1252-5.
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14. Nickel JC, Downey J, Pontari MA, Shoskes DA, Zeitlin SI. A randomized placebo-controlled multicentre study to evaluate the safety and efficacy of finasteride for male chronic pelvic pain syndrome (category IIIA chronic nonbacterial prostatitis). BJU Int 2004; 93(7):991-5.