Chronic Pelvic Pain in Men 

Updated: Mar 17, 2020
Author: Richard A Watson, MD; Chief Editor: Edward David Kim, MD, FACS 

Overview

Practice Essentials

The term chronic pelvic pain syndrome (CPPS) is used to designate unexplained chronic pelvic pain in men. This pain is associated with irritative voiding symptoms and/or pain in the groin, genitalia, or perineum in the absence of pyuria and bacteriuria (no pus cells or bacteria seen on microscopic analysis of the urine). However, excess white blood cells (WBCs) or bacteria seen on Gram stain and culture of expressed prostatic secretions (EPS) may be found. (See Workup.)

CPPS has also been termed prostatodynia; however, the use of this term is not encouraged in current practice, as it carries the negative historical connotation of being a "wastebasket" designation for a melange of psychosomatic symptoms and suggests that the source of the patient's symptoms invariably lies within the prostate gland itself. Current research has provided evidence of numerous extraprostatic considerations, including neuropathic and other systemic pathologies. (See Etiology.)

The National Institutes of Health (NIH) describes four categories of prostatitis, as follows:

  • Type I – Acute bacterial prostatitis
  • Type III – Chronic abacterial prostatitis (ie, CPPS, categorized as either type IIIa [inflammatory CPPS] or type IIIb [noninflammatory CPPS])
  • Type IV – Asymptomatic inflammatory prostatitis

An academic distinction is currently made between (1) patients with excess WBCs in their prostatic secretions (chronic nonbacterial prostatitis, class IIIa) and (2) those with normal prostatic secretions (prostatodynia, class IIIb). However, the clinical value of this distinction is now being challenged. The sole parameter is the number of WBCs seen within a smear of prostatic secretions, yet this number may vary widely within the same specimen and even more so from sample to sample taken from the same patient. (See Workup.)

Furthermore, significant numbers of WBCs have also been found in the prostatic secretions of asymptomatic control patients with no evidence of pelvic pathology. At present, the distinction between class IIIa and IIIb CPPS seems to provide no meaningful differential with respect to either etiology or treatment options.

No known cure exists for CPPS. However, many medications and other forms of treatment can help to alleviate the symptoms of CPPS and make the condition more bearable. (See Treatment and Medication.) Over time, this condition may improve or stabilize on its own. The Prostatitis Expert Reference Group, a United Kingdom organization, has published a consensus guideline that includes recommendations for the treatment of CPPS[1] (see Guidelines).

 

Etiology

Chronic pelvic pain syndrome (CPPS) in the male is actually not a syndrome, in that it is not a discrete, narrowly defined constellation of consistent symptoms and objective findings ultimately traceable to a single, known etiology. Rather, CPPS in the male is a catch-all category of convenience into which physicians arbitrarily group the heterogeneous admixture of cases in male patients that meet the following three criteria:

  • Patients have a variety of long-standing symptoms, a significant number of which relate to anatomical structures located within an arbitrary radius of the prostate gland (somewhere below the umbilicus and above the mid-thigh)
  •  Physicians can find no objective explanation for the patients’ symptoms
  •  Physicians can offer no satisfactory treatment, let alone a cure, for the patients’ symptoms

Pontari and Ruggieri reviewed the numerous pathophysiologic mechanisms implicated as the potential etiologies of CPPS and concluded that, although the causes of CPPS remain unknown, the condition’s symptoms seem to arise from the interaction between psychological factors and immune, neurologic, and endocrine system dysfunction.[2]

The number of WBCs (pus cells) found in the prostatic fluid under microscopic examination—long considered the hallmark of this disease process—does not correlate with the degree of pain or with other symptoms experienced by patients with CPPS. Histologic signs of inflammation were found in only one third of all patients diagnosed with CPPS who underwent prostatic biopsy, according to Pontari and Ruggieri’s report, further suggesting an extraprostatic etiology for CPPS. This indicated that perhaps CPPS is not directly associated with the prostate or with inflammation within it, at least in some cases.

Special signaling molecules called cytokines, which are produced by WBCs (and by other cells), may play a role. While certain cytokines stimulate an inflammatory reaction, others inhibit inflammation. Moreover, the same cytokine may have either an inciting influence or an inhibiting influence at different sites under varying conditions.

Tissue necrosis factors, interleukins, interferons, and epithelial neutrophil-activating factors are but a few of these cytokines. To complicate matters, each of these terms indicates a whole, separate family of closely related molecules, not a single agent. An imbalance in this complex network of cytokines (ie, of proinflammatory cytokines and endogenous cytokine inhibitors) has been linked to the development of pelvic inflammation and pain in patients with CPPS.

Genetic predisposition to CPPS may be the result of differences in DNA sequences at chromosomal sites that regulate the production and action of these various cytokines.

Autoimmunity has long been thought to play a role in the development of CPPS. In this context, immunity refers to the body's ability to reject foreign material, such as bacteria or toxins. This process can sometimes turn on itself and lead to rejection of the body's own healthy tissues. In CPPS, the body may be attempting to reject its own prostate.

Testosterone has been shown to protect against inflammation within the prostate. Perhaps a low testosterone level (or, more likely, a breakdown in the mechanism whereby testosterone inhibits prostatic inflammation) may be at work in some men with CPPS.

Abnormal functioning of the nervous system, at the local level and/or within the central nervous system (CNS), may also play a role in the development of CPPS. For example, a substance known as nerve growth factor (NGF) can cause an increase in the number and the sensitivity of the pelvic nerves that transmit pain. An increase in NGF has been correlated with the development of CPPS symptoms.

Each of the above factors has been individually identified as a culprit in the pathogenesis of CPPS; additionally, at least in some cases, they may interact with each other to cause CPPS. For instance, cytokines may adversely affect the suppression of NGF, leading to a flare of CPPS symptoms.

Psychological stress and depression have long been associated with CPPS flare-ups. This observation has led some researchers to mistakenly conclude that CPPS is "all in your head” or that such mental stress results in a lower psychological threshold for the same objective degree of pain. Data now suggest, however, that psychological stress and depression may measurably influence the local production of cytokines (eg, interleukin-10, interleukin-6) in the pelvis, thus directly exacerbating CPPS inflammation.

Some cases of "abacterial" prostatitis may not actually be abacterial. Data suggest that gram-positive bacteria, which have traditionally been dismissed as normal flora in prostatic fluid cultures, may not be so normal in men with CPPS. Normal defense mechanisms allow healthy men to render these bacteria harmless, turning them into mere microbial "hitchhikers." However, these defense mechanisms may be defective in men with CPPS. This theory helps to explain why prolonged courses of antibiotics sometimes provide symptomatic relief for men with CPPS despite the absence of bacteria that are traditionally considered pathogenic.

Pontari and Ruggieri conclude, "To what degree these factors interact in a given patient and to what degree there is a common pathway or several pathways that lead to the end point of pelvic pain remains to be determined."[2]

Fastidious organisms in CPPS

Among the fastidious bacteria (ie, bacteria that cannot be isolated on standard culture media) that have been implicated in CPPS are the following:

  • Chlamydia trachomatis
  • Genital mycoplasmas (ie, Ureaplasma urealyticum, Mycoplasma hominis, M genitalium)
  • Neisseria gonorrhoeae
  • Anaerobic bacteria
  • Gram-positive bacteria

The following organisms have also been implicated:

  • A protozoan (ie, Trichomonas vaginalis)
  • Genital tract viruses (eg, herpes simplex virus types 1 and 2, cytomegalovirus, human papillomavirus-16 [3] )
  • Fungi

In a study by Krieger and Riley, only 10 (8%) of 135 patients with chronic prostatitis (CP)/CPPS tested positive for fastidious organisms. However, in another series, 79 (47%) of 170 specimens from patients with CP/CPPS exhibited gene sequencing (16S ribosomal DNA) that was positive for the presence of microbes, while only 21 (20%) of 117 control specimens from patients undergoing radical prostatectomy were positive (P< 0.01). These observations support a potential role for uncommon organisms in CP/CPPS.[4]

Bacteriologic breakthroughs in understanding CPPS

Intriguing findings from collaborating investigators in Australia and California suggest that persistent microbial infection with Propionibacterium acnes, an indolent but persistent organism that is difficult to detect and difficult for the host to eradicate, may act as an etiologic agent for CP and for the subsequent development of prostate cancer. These investigators found that P acnes could not be identified using routine histology, Gram stain, or routine culture techniques; its presence could be detected only via sophisticated gene-sequencing and polymerase chain reaction (PCR) assay technology.[5]

These preliminary findings suggest that chronic abacterial prostatitis may, in certain cases, actually be due to an occult, chronic bacterial infection. Further, persistence of this smoldering infection may lead to the development of prostate cancer.

Confirmation of these findings, along with the identification of effective methods to eradicate these bacteria, could lead to cure and prevention, at least in some cases, of CP and prostate cancer.

Escherichia coli infection is a common cause of acute bacterial prostatitis. However, these bacteria cannot be cultured in patients with chronic abacterial prostatitis. Certain strains of these bacteria may have developed a cloaking defense that allows them to conceal their activity and to resist antibiotic therapy.

Laboratory studies suggest that specific strains of E coli are specifically uropathogenic (ie, uropathogenic E coli [UPEC]). These UPEC bacteria have the capability of penetrating into prostate cells. Once they have invaded prostate cells, they trigger a genetically linked reaction that sustains the pain by immunological and/or neurological mechanisms, even after the bacteria have been eradicated. These findings might help explain why antibiotics can be helpful in treating an initial bout of acute prostatitis, and yet be ineffective in relieving subsequent bouts. Only certain strains of E coli are capable of invading the prostate cell; some men may be more at risk than others.[6]

Biofilms develop when large numbers of bacteria embed in a microscopic slime layer called an exopolysaccharide matrix. Entrenched within this biofilm layer, the bacteria may resist antibacterial treatment, counter the human body's natural defenses, and defy detection by routine culture techniques.

By forming these biofilms within the prostate, E coli and related bacterial pathogens may cause chronic, treatment-resistant prostatitis. In some cases, they may also be the cause of chronic abacterial prostatitis. Prolonged (6-wk) courses of effective antibiotics (eg, a quinolone), when used to treat the first bout of acute prostatitis, may prevent the bacteria from forming a biofilm. Early, vigorous treatment of the first case of prostatitis using this method may help to prevent the inflammation from progressing into the chronic phase of bacterial or abacterial prostatitis.[7]

Neuropathy in CPPS

Findings of spastic hyperactivity on videourodynamic studies, in the absence of a definable underlying neuropathy, suggest the presence of either an occult neural etiology or an acquired functional voiding disorder.

Myofascial pain syndrome has been postulated as a cause for CP/CPPS. Even in the face of clinical inflammation, a reflex triggering of spasm in the musculature of the pelvic floor can be a secondary, but clinically significant, source of much of the symptomatology.[8]

Immunology in CPPS

An autoimmune basis for chronic prostatitis has been well established in different murine models. Unfortunately, a clinical correlation in humans has not yet been well elucidated.

Stromal cells in benign prostatic hyperplasia (BPH) tissue have been shown to be capable of acting as antigen-presenting cells and activating CD4(+) lymphocytes, as well as producing interleukins.[9]

Several studies now demonstrate that men with CP/CPPS show evidence of having a “pan-pelvic hypersensitivity syndrome.” Using the fibromyalgia tender point scale, men with CP/CPPS tend to be more tender than normal, not only in the pelvic region, but also at every other point throughout their entire body. Whatever causes CP/CPPS leads to a serious and hard-to-treat hypersensitivity of the entire central nervous system. This difference in lowered pain tolerance holds true, whether or not the CP/CPPS patient was experiencing a flare-up of prostatitis.[10]

Epidemiology

In the United States, chronic prostatitis (CP) is the most common urologic diagnosis in men older than age 50 years and is the third most common diagnosis in men younger than age 50 years. This diagnosis results in at least 2 million office visits per year. The average urologist sees approximately 10 patients with prostatitis per month, 30% of whom are new patients. Specific urinary pathogens are detected infrequently after culture. The vast majority of these patients are categorized as having chronic nonbacterial prostatitis, that is, CPPS.

Patient Education

The following Web sites are helpful for both patients and physicians:

  • The International Association for the Study of Pain special interest group on Pain of Urogenital Origin (PUGO)

  • Prostatitis Foundation

  • Chronic Prostatitis/Chronic Pelvic Pain Syndrome Network

For patient education information, see Pelvic Pain.

 

Presentation

History

Symptoms parallel those experienced by persons with chronic bacterial and nonbacterial prostatitis. The typical patient is a young to middle-aged man with variable symptoms of chronic, irritative, and/or obstructive voiding accompanied by moderate to severe pain in the pelvis, lower back, perineum, and/or genitalia.

Erectile dysfunction is the symptom that initially brings many men to seek medical attention; however, the patient often waits until the end of the interview to mention the problem or he may avoid mentioning it at all unless the physician specifically inquires.

To facilitate history taking and to establish a more uniform standard, a National Institutes of Health (NIH) collaborative panel proposed the Chronic Prostatitis Symptom Index (NIH-CPSI). This index is calculated using a series of nine questions that contain 21 items used to assess patient history in a standardized and quantifiable format. The questions cover pain, urinary symptoms, and impact of symptoms on quality of life. Each category generates separate scores; a total score is also calculated.

Physical Examination

No physical examination finding in chronic pelvic pain syndrome (CPPS) is pathognomonic. Examination of the genitalia reveals normal results. Digital rectal examination may reveal a tight anal sphincter. When the anal sphincter tone is hyperactive, a verifiable spastic neuropathy must be excluded. The hyperactivity may otherwise indicate a spasmodic hyperirritability of the pelvic floor musculature, which may be amenable to medical and biofeedback therapies.

The prostate and adjacent tissues may be moderately to severely tender, and the gland itself may be slightly congested or boggy. However, the presence of a small, relatively firm gland does not exclude the possibility of CPPS type III. Extreme tenderness upon gentle palpation of the prostate should raise suspicion for acute bacterial prostatitis or even a prostatic abscess.

The value of this examination is to exclude other diagnoses, such as prostate cancer, chronic urethritis/meatitis, and granulomatous prostatitis.

 

DDx

Diagnostic Considerations

The many differential diagnoses associated with chronic pelvic pain syndrome (CPPS) reveal the conundrum of diagnosing this condition. Because the diagnosis is one of exclusion, in theory, this diagnosis cannot be made until all of these alternatives have been definitively excluded. However, time, patience (the physician's and the patient's), limited medical resources, and/or the patient's finite financial resources preclude a categorical demonstration of the absence of each of these symptomatically related entities.

Conditions to consider in the differential diagnosis of CPPS include the following:

  • Inflammatory bowel disease
  • Nonbacterial prostatitis
  • Acute bacterial prostatitis
  • Prostate cancer
  • Tuberculosis of the genitourinary system
  • Urethral cancer
  • Urethral diverticula
  • Urethritis
  • Tuberculous prostatitis
  • Sexually transmitted diseases
  • Congenital or acquired abnormalities of the urethra
  • Prostatic cyst
  • Prostatic abscess
  • Seminal vesiculitis
  • Myofascial pain syndrome
  • Reactive arthritis
  • Pelvic joint dysfunction
  • Coccydynia
  • Chronic urethritis
  • Interstitial cystitis
  • Carcinoma in situ of the urinary bladder

CPPS versus interstitial cystitis

An archetypical example would be differentiating between prostatodynia and interstitial cystitis in the male. The distinction between prostatodynia and interstitial cystitis is particularly challenging because both conditions are diagnoses of exclusion (ie, two separate "wastebasket" diagnoses). No diagnostic test can be used to definitively establish or to exclude the diagnosis of either prostatodynia or interstitial cystitis.

If cystoscopy is planned as part of the workup, performing this study with the patient under anesthesia and including a bladder biopsy and hydrodistention to search for indicative signs is prudent and cost effective.[11] However, the pathognomonic Hunner ulcer of interstitial cystitis is as rare as it is classic. Additionally, the presence of glomerulations—not always an all-or-none observation—has been described in asymptomatic women.

At the 2001 convention of the American Urological Association, no fewer than three reports disparaged the utility of the once heavily promoted potassium sensitivity test. Conversely, Parsons and Albo found that the response to the potassium sensitivity test in 40 men with chronic prostatitis (CP) was comparable with that expected in women with interstitial cystitis. They concluded that prostatitis and interstitial cystitis in men may be part of a continuum of lower urinary dysfunctional epithelium.[12]

In 2004, Forrest and Schmidt reviewed a series of 92 men diagnosed with interstitial cystitis, most of whom had been referred for urologic evaluation with an initial diagnosis of either CP (54%) or benign prostatic hyperplasia (23%).[13] Interstitial cystitis had been diagnosed in these patients according to standard National Institute of Diabetes and Digestive and Kidney Diseases (NIDDKD) criteria and confirmed by the presence of severe glomerulations or Hunner ulcers on the bladder wall after hydrodistention. Forrest and Schmidt cautioned that the symptoms of interstitial cystitis closely parallel those of CP/CPPS.

The patients’ presenting symptom was most often only mild discomfort in the suprapubic area. However, their symptoms rapidly worsened; within less than 3 years, they had marked suprapubic pain, severe dysuria, and debilitating urinary frequency, during daytime and nighttime. Sexual dysfunction was an issue for 60% of these men, with painful ejaculation being the most frequently expressed symptom. Low back pain, perineal pain, and testicular pain were reported by 50% of these patients. Symptoms were so severe that total cystectomy was performed as a last resort in two of these patients. (As a side note, these researchers observed an unusually high prevalence of interstitial cystitis among Native American [Cherokee] men.)[13]

The point at which the physician empirically recommends (for a given patient with CPPS) a trial of therapies specific for interstitial cystitis is based on the physician's judgment. For example, therapies such as pentosan sulfate (Elmiron) and intravesical instillations of dimethyl sulfoxide (DMSO) have yielded success in selected patients with prostatodynia.

Details regarding the array and application of various interstitial cystitis therapies are beyond the scope of this article. Nonetheless, the frustrated diagnostician should keep this option for diagnosis in mind when further evaluating a patient with refractory prostatodynia. Similarly, other diagnoses also must be excluded.

CPPS versus chronic urethritis

The distinction between chronic urethritis and CP/CPPS can prove problematic, an issue discussed by Krieger and Riley.[4] Of the seven symptoms evaluated in the NIH Chronic Prostatitis Symptom Index, three symptoms are common to both populations: penile pain, urinary frequency, and dysuria. The remaining four symptoms are typical of CP/CPPS alone: perineal pain, pain in the testicles, pain in the suprapubic area, and pain upon ejaculation. Conversely, urethral discharge was characteristic of nongonococcal urethritis (NGU) but was not specifically reported in cases of CP/CPPS. Urethral WBCs were identified in all patients with NGU and in 50% of those with CP/CPPS.

CPPS versus cancer

Any risk of underlying cancer must be addressed urgently. Transitional cell cancer and carcinoma in situ of the bladder are deadly masqueraders. Prostate cancer can also manifest as symptoms that suggest prostatodynia. Neoplasms of the rectum and GI tract and rare tumors of other pelvic organs have manifested as irritative prostatic symptoms. Benign prostatic hyperplasia and obstructive uropathy also manifest in this manner. All of these possible diagnoses must be considered when diagnosing prostatodynia.

Older men who experience the symptoms of CPPS for the first time may understandably be concerned that these symptoms represent underlying cancer of the bladder or prostate, but they may be reluctant to openly voice this anxiety. Once the diagnosis of cancer has been firmly ruled out, the patient must be reassured that this possibility has been carefully considered and excluded.

Ignoring these possibilities in patients with CPPS may eventually prove to be a fatal mistake. However, to subject every patient to a physically and financially exhaustive gauntlet of tests and procedures is also clearly inappropriate. Tailoring the diagnostic workup to meet the needs of a specific patient is a skill that defies textbook codification. The art of medicine comes into play in deciding, together with the patient, which possibilities to pursue and how vigorously to pursue each of them.

Standard teaching has been that men with CPPS have no increased risk of prostate cancer. However, a study from Case Western Reserve revealed that patients who underwent an initial prostate biopsy that was negative for cancer but positive for CP were at higher risk of subsequently developing cancer than were men who underwent prostate biopsy that was negative for cancer and for prostatic inflammation.[14] However, the researchers did not recommend any change in current recommendations, pending confirmatory studies. Meanwhile, patients with CPPS should adhere strictly to standard recommendations for prostate cancer screening.

Differential Diagnoses

 

Workup

Approach Considerations

Because chronic pelvic pain syndrome (CPPS) is a diagnosis of exclusion, review the patient's records and perform a thorough physical examination to eliminate the possibility that another, more treatable disease is causing these symptoms. Assure the patient that only diagnostic tests that hold a reasonable chance of producing a significant result will be recommended. The patient should not rule out the possibility that these examinations may reveal an alternate diagnosis, but he should also know that he will not be burdened by excessive testing.

Excluding potentially fatal conditions (eg, prostate cancer, obstructive uropathy, pyonephrosis, bladder cancer, carcinoma in situ of the bladder) to any reasonably possible extent is imperative. Further, remember that patients with a documented, long-standing diagnosis of prostatodynia are not exempt from the development of any of these and other serious conditions.

Periodically, particularly in the setting of a flare-up of symptoms, a streamlined repetition of basic screening investigations should be judiciously undertaken. This may include the following:

  • Thorough physical examination with digital rectal examination of the prostate
  • Prostate-specific antigen (PSA) measurement
  • Urine culture and cytology
  • Renal and/or bladder ultrasonography or intravenous pyelography

Imaging studies

Because no diagnostic finding for CPPS has proven definitive, all imaging studies (eg, kidney, ureter, and bladder radiography; intravenous pyelography; videocystourethrography; computed tomography [CT] scanning; magnetic resonance imaging [MRI]; ultrasonography of the scrotum; transrectal ultrasonography of the prostate) are aimed at excluding the presence of other, more definable and treatable causes of the patient's symptoms. None of these studies warrants universal application.

A cost-effective diagnostic algorithm should be individualized for each patient suspected of having CPPS, incorporating only laboratory tests and imaging procedures that are appropriate to that specific patient's problem.

Flow rate

A formal flow rate study often shows intermittency of flow and weakening of the urinary stream with a diminished peak urinary flow rate. The urethral pressure profile typically shows a high maximum urethral closing pressure.

Urinalysis and Culture

No tests exist for which the results unequivocally indicate the diagnosis of chronic pelvic pain syndrome (CPPS). The presence of pyuria, bacteriuria, or both supports a diagnosis of bacterial prostatitis.

The presence of an inordinate number of white blood cells (WBCs) in expressed prostatic secretions (EPS) and/or bacteria on Gram stain and/or a heavy, nearly pure growth of a known bacterial pathogen on culture indicate a diagnosis of bacterial prostatitis. However, contamination from the urethra, an external site, or a source of infection in the upper urinary tract can lead to a false-positive result, while errors in collection or processing can lead to a false-negative result.

The National Institutes of Health Chronic Prostatitis Cohort Study, in reviewing the screening results from 488 men with chronic prostatitis (CP), CPPS, or both, found (discouragingly) no reliable correlation between the leukocyte counts or the bacterial counts and the degree of symptomatology, whether the analysis was performed on the EPS, the postmassage voided urine (ie, the third midstream bladder specimen [VB3]), or the ejaculate. The authors concluded that factors other than leukocytes and bacteria must contribute to symptom development in men with CPPS.[15]

Stamey recommended the three-glass urinalysis method, and, while this approach is widely taught, it is much less widely practiced by clinical urologists today. Nickel suggested that a simplified premassage and postmassage test may prove more efficacious.[16]

Prostatic massage (diagnostic) and three-glass urinalysis

Massaging the prostate produces EPS. The finding of high colony counts of bacterial pathogens and/or a significant excess of WBCs suggest the presence of a treatable infectious agent, particularly if these findings can be reproduced after a second massage. However, because eliminating urethral contaminants from these specimens is impractical, the clinical reliability of these findings is subject to challenge.

Most men find this process distinctly unpleasant, and many find the procedure greatly difficult or impossible to tolerate.

In many cases, no prostatic secretion flows from the meatus after massage. In these cases, Stamey recommends obtaining the first 10 mL of voided urine immediately following massage, a VB3, and submitting that specimen for Gram stain and culture as a substitute for the EPS.

Prostate-Specific Antigen Study

The PSA level is often elevated in men with acute bacterial prostatitis and may also be modestly elevated in those with chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS).

PSA testing in men with CPPS symptoms may be helpful in distinguishing between chronic bacterial prostatitis (as indicated by an elevated PSA value) and CPPS (as indicated by a PSA value within the reference range).[17] However, this theory has yet to be tested in a well-controlled clinical trial. Moreover, testing the theory presents problems because researchers would have to counsel large numbers of men who are younger than age 40 years and who have an elevated PSA value secondary to benign prostatic inflammation that their elevated PSA test result is not an indication of prostate cancer.

Urine Cytology

Voided urine cytologies, while not routine, should be readily considered whenever the index of suspicion is at all elevated, as it would be, for instance, in patients who have had a long history of smoking, who have had occupational exposure to known toxins, or who exhibit persistent microhematuria. When such a patient is undergoing cystoscopy, bladder-wash cytology should be obtained.

Carcinoma in situ, at times, presents as a velvety patch of mucosa, but often it may be indistinguishable from normal urothelium.

Videourodynamics

Videourodynamic evaluation often reveals evidence of a spastic dysfunction of the bladder neck and prostatic urethra. Beyond helping to detect occult neuropathies, urodynamic evaluation of patients with chronic pelvic pain syndrome (CPPS) type III may lead to a better understanding of the underlying voiding dysfunctions peculiar to select subsets of patients with this condition. Nickel contends that dysfunctional voiding and intraprostatic reflux of urine may be initiating factors in the onset of CPPS type III.[16]

Additionally, by subcategorizing patients with CPPS type III based on the presence and the nature of abnormal urodynamic findings, an improved rationale for case-specific therapies may be forthcoming.[18]

Incomplete relaxation of the bladder neck and abnormal narrowing of the prostatic urethra occur on voiding views.

These findings alone might not clearly justify the expense and discomfort associated with the procedure. The main role of urodynamic studies is to rule out another underlying, unsuspected, but well-defined neuropathy amenable to treatment.

Cystoscopy

Although the study results may be entirely normal, cystoscopy, at most, reveals only nonspecific findings of minimal to mild inflammation and congestion in the area of the trigone and prostatic urethra. The main purpose of this intervention is, as with uroradiography, to help rule out the presence of other causes of the patient's symptoms.

Cystoscopy can be performed in an outpatient setting after urethral injection of lidocaine (Xylocaine) jelly. However, cystoscopy under general or regional anesthesia or under conscious sedation offers a couple of advantages. As a rule, patients with chronic pelvic pain syndrome (CPPS) tend to be hypersensitive with a low pain tolerance. When the patient is unable to cooperate fully, endoscopic inspection is compromised.

In addition, general or regional anesthesia allows for more comfortable performance of cold-mucosal cup biopsies to rule out carcinoma in situ and for hydrodistention of the bladder to rule out interstitial cystitis. Also, minor pathology, such as an annular stricture of the urethra or a prostatic polyp, can be treated at the same time.

Anal Sphincter EMG and/or Sphincter Function Profiles

With anal sphincter electromyography (EMG) and/or sphincter function profiles (microtip catheter), the reflex reactivity during cystometrography is recorded, and findings indicate the presence of hypertonicity and failure of the pelvic floor musculature to relax. These are signs of an underlying myofascial pain syndrome. Overall pelvic floor activity during cystometrography can also be monitored via an intra-anal surface electrode.

While such experimental evaluations are not yet part of the standard urological armamentarium, they are available at select centers.[8]

 

Treatment

Approach Considerations

Chronic pelvic pain syndrome (CPPS) is a well-established condition that is notorious for the pain and disability it causes. Treating CPPS challenges even the most compassionate physician; patients are often understandably tense, wary, and defensive, and most of them will have already encountered frustration and rejection under the care of several unsympathetic physicians. These patients often approach new physicians with an off-putting combination of unrealistic hopes for a cure and suspicion related to past diagnosis and treatment failures.

The patient and physician must agree on a workable relationship at the outset of treatment. The urologist and patient may wish to address several points, perhaps approaching treatment as a contractual agreement. Severely disabling CPPS has been treated with transurethral resection of the prostate (TURP) and even radical prostatectomy. (Radical prostatectomy is an extreme measure; consider this treatment only in the most desperate of cases, if at all.[19] )

Initial points to address

As previously stated, CPPS is, despite its name, a condition, not a disease or syndrome. It is similar to other chronic conditions, such as arthritis, that, while treatable, are not curable. No known cure exists for CPPS, but treatments based on the cooperation of patient and physician makes this condition more bearable. Over time, this condition may improve or stabilize on its own.

Many medications and other forms of treatment can help to alleviate the symptoms of CPPS. However, being patient is important; try only 1 or 2 new treatments at a time, giving each enough time to take effect. Do not overwhelm the patient with an unreasonable number of simultaneous treatments, which causes only excessive inconvenience and expense. Simultaneous treatments might actually work against one another, and the adverse effects of these treatments might cause more, rather than fewer, problems for the patient.

Reassure the patient that CPPS is a real physical condition, not an imagined one. However, this devastating problem causes many psychological stresses for the patient; therefore, suggest medications to help calm the patient and offer consultation with a psychiatrist or psychologist. A mental health care professional who has a special interest in this area may prove beneficial. Urologists and other clinicians need to be attentive to the profound psychological impact of CP/CPPS, as research has suggested that newly diagnosed CP/CPPS patients may be more likely to develop a depressive disorder.[20]

Reassure the patient that CPPS is not cancer, not a life-threatening condition, not a venereal disease, and not contagious. Explain that the patient did not acquire this condition from someone else, nor will he pass it on to anyone.

In addition, remind the patient that he is not alone, that many men experience this problem. Local and national support groups recommended by the physician can provide additional information and encouragement.

Agree on a schedule of planned follow-up visits performed as frequently as appropriate management of symptoms dictates. These scheduled appointments minimize the need for emergency visits and telephone calls while providing comfort and creating trust between doctor and patient.

The urologist institutes treatment through, and in close communication with, the patient's primary care physician, who remains the mainstay of care.

Remind the patient that he is free to seek the advice of other physicians and health care providers while he is under a urologist's care. However, the patient must keep the urologist informed of all other treatments and medications tried, including alternative medicines and home remedies.

Remind the patient that his problem is taken very seriously and that every effort will be made, with the patient's cooperation, to minimize the problems that this condition causes. The patient-physician relationship should be a partnership formed to gain control of this condition and allow the patient to more fully enjoy life.

Prevention

Until the etiology of CPPS is known, no specific preventative strategy will be available. In some patients, this condition may be caused by the sequela of sexually transmitted disease. In such cases, more vigorous treatment of the sexually transmitted disease and/or more lengthy antibiotic treatment (>4 wk) for an initial bout of acute prostatitis may reduce the percentage of cases that progress to a chronic, incurable state.

The UPOINT system

Men with CPPS present with various symptoms. Moreover, the intensity of symptoms varies. Researchers have developed a categorization (the UPOINT classification) to separate patients into subgroups, according to which symptoms predominate.[21] The hope is that by characterizing the set of symptoms that are specific for each given patient, treatment can be more accurately tailored. Furthermore, the categorization allows investigation into the success of various medications and treatments based on symptom subgroups.

The UPOINT classification has a 6-point system, as follows:

  • U - Urinary symptoms
  • P - Psychosocial symptoms
  • O - Organ-specific symptoms (such as the prostate)
  • I - Infection-related symptoms
  • N – Neurologic/systemic symptoms
  • T - Tenderness in the muscles and pelvic floor symptoms

In one clinical setting, 22% of patients with CPPS had symptoms limited to a single domain. The percentage of patients with symptoms in a given dominion ranged from as high as 52% of patients experiencing urinary symptoms to as low as 16% experiencing infection-related symptoms.

Many times, trials of medication have failed to show a successful outcome in terms of overall improvement. However, when researchers reassessed the results in terms of improvement in one particular domain or problem area, they occasionally uncovered a noticeable improvement. For instance, use of alpha-blockers, such as alfuzosin (Uroxatral) or tamsulosin (Flomax), did not seem to have a significant impact when the response in terms of overall symptoms was measured as the single endpoint. However, a hopeful response was detected when the researchers went back and looked at responses specifically within the urinary domain.[21] Patients with predominantly neuropathic pain may benefit from pregabalin (Lyrica) and related mediations, whereas other patients may not.

Thus, although some medications have failed to achieve a measureable improvement in symptoms among all patients, they may actually be helpful for certain patients within a given domain or symptom subset. Medications that have been rejected in the past because most men experienced no improvement in terms of overall response may actually prove helpful for small subset of men who share a certain symptom.

The theory behind this classification of has been named the “snowflake hypothesis” because the 6 domains can be arrayed in a diagram like a snowflake. A Web site has been established to assist physicians in deriving a UPOINT score for their individual patients, available at UPOINTmd.com.

More recently, a seventh domain has been proposed for symptoms related to sexual function.[22] Current validation studies confirm that the 6 UPOINT categories do remain internally consistent, with the exception of the organ-specific category, which seems to contain 2 separate subgroups: one for men predominantly with bladder symptoms and one for those with prostate symptoms.

Moreover, these 6 UPOINT domains seem to interrelate or cluster into 2 major divisions. Patients with symptoms in any one of the 3 categories that are specific to the pelvis (urinary, organ-specific, and tenderness) have more in common. Conversely, men with symptoms that are predominantly in one of the 3 systemic domains (neurologic, infection-related, and psychosocial) seem to have a common bond.[23]

Research has shown that if patients are identified by their UPOINT phenotype and treated accordingly, the response rate is 84%, with a Chronic Prostatitis Symptom Index (CPSI) score decrease of 12 points, from 25.2 to 13.2.[24]

The UPOINT classification may help separate men with specific sets of symptoms who may be helped by a given medication targeted at relieving their particular symptom subset, even if other patients with different UPOINT classifications do not benefit.

Prostatic Massage (Therapeutic)

In therapeutic prostatic massage, the physician places a finger rectally over the back of the prostate gland (as is performed during a routine prostate examination) and presses firmly and methodically down upon the entire surface gland, working from the lateral edge centrally, with the goal of breaking open prostatic ducts that have become plugged with inspissated material and expressing the released secretions into the urethra.

The role of prostatic massage in providing symptomatic relief is controversial. With little evidence-based medicine to recommend it, regularly repeated prostatic massages have been recommended in the past, particularly for patients with a large, congested gland. Some patients find that massage provides temporary relief that is worth the awkwardness and discomfort of the maneuver itself.

In 1969, Winter recommended prostatic massage 1-3 times weekly for 3-4 weeks for chronic infection of the prostate. Although this maneuver has largely fallen out of favor with many contemporary urologists, some still revert to it, albeit on a less frequent schedule, to provide supplementary symptomatic relief for select patients.

Therapeutic Ejaculation

The role of frequent ejaculation in either producing or reducing CPPS symptoms remains controversial. Patients with enlarged, symptomatically congested glands are often advised that regular sexual intercourse may alleviate their symptoms. While little objective evidence substantiates this claim, most patients find this recommendation more attractive than serial prostate massages by their local urologist.

Whether frequent sexual intercourse relieves or actually exacerbates the condition seems to vary idiosyncratically from patient to patient.

The primary author's anecdotal observation is that patients tend to be most adversely affected by sudden, dramatic changes in the frequency of intercourse, either increase or decrease. For example, a patient who remains sexually abstinent while on prolonged business trips is apt to experience a flare-up of CPPS when he leaves home and again when he returns.

Whether masturbation produces an effect comparable to that of intercourse remains as unproven as it is widely advised. Ironically, similar prostatic maladies were attributed in 19th-century medicine to an excess of masturbation; what was condemned as a cause of prostatitis in the 1800s is being promoted as a cure in the 20th century. Before recommending masturbation, bear in mind that this is a sensitive subject; this activity is objectionable to some patients' moral and religious standards.

Transurethral Resection of the Prostate

A widely held opinion among urologists is that transurethral resection of the prostate (TURP) should be a rarely used approach of last resort, offered only by experienced resectionists to patients who have experienced extreme, persistent symptoms over a protracted period, with no relief from nonoperative interventions. Candidates for TURP must understand clearly that symptomatic relief is not guaranteed. Indeed, symptoms may even worsen and could be compounded by the added burdens of erectile dysfunction and urinary incontinence.

When TURP is undertaken, completing a thorough resection of all tissues, down to the capsule, is essential. The concern is that residual tissue, partially coagulated, with obstruction of the ductal drainage from prostatic acini, might exacerbate the patient's symptoms.[25]

Myofascial Release Therapy and Paradoxical Relaxation

Myofascial release therapy is a combination of internal and external trigger-point release therapy. It has proven more effective than standard external massage therapy alone.

Paradoxical relaxation is a methodology used to train autonomic self-regulation and pelvic muscle tension release. This psychotherapeutic treatment technique is used to help the patient decrease anxiety and nervous system arousal while counteracting the habit of tensing the pelvic muscles under stress. It is termed "paradoxical" because patients are directed to accept their pain and tension as a way of relaxing or releasing it. This approach incorporates group therapy, breathing techniques, and behavioral therapy, among other elements, to help reduce CPPS symptoms.

Anderson et al have developed a protocol that employs a team composed of a urologist, psychologist, and physiotherapist to provide a multifaceted approach to treating patients with CPPS and educating them on how to effectively alleviate their symptoms. This "Stanford protocol" incorporates myofascial trigger point assessment and release therapy, as well as paradoxical relaxation therapy.[26]

Urologic evaluation is completed by the urologist, while myofascial trigger point assessment and release therapy is performed by the physical therapist, and techniques of paradoxical relaxation are taught by the psychologist. This novel approach capitalizes on the patient's own involvement in the treatment of CPPS.

Patients are taught the anatomy of the pelvic floor and lower abdomen and instructed on how to effectively manipulate their trigger points. Patients are also taught methods of relaxation in order to relieve autonomic dysfunction. A study showed an improvement in pain and urinary symptoms in 72% of patients with refractory CPPS following intensive Stanford protocol therapy.[26]

The widespread acceptance of this approach among practicing urologists awaits further demonstration of its reproducibility and efficacy in multiple medical centers with larger numbers of patients and a greater variety of practitioners.[27]

A readable text that describes this approach to the evaluation and management of CP/CPPS and that might prove helpful to clinicians and patients alike is A Headache in the Pelvis: A New Understanding and Treatment for Prostatitis and Chronic Pelvic Pain Syndrome by Wise and Anderson (2003).[28]

Additional Treatments

Dietary considerations

The influence of diet on chronic pelvic pain syndrome (CPPS) varies. Traditionally, patients have been warned to avoid excessive intake of prostate irritants, such as tobacco (smoking), coffee, tea, soda (cola drinks and diet drinks may be especially irritating), caffeine, spicy foods, and alcohol.

Inform the patient that none of these items is known to cause actual physical damage or to worsen the long-term prognosis. Nevertheless, responsible limitation of these items may help to control the day-to-day symptoms. A glass or two of wine or sherry may lessen nocturia symptoms.

Alkalinization of the urine seems to help some patients. A teaspoonful of baking soda (sodium bicarbonate) in a tall glass of warm water taken at bedtime may help to reduce nighttime symptoms. However, caution patients regarding the risk of an excessive sodium load with higher oral intakes, especially in patients receiving treatment for hypertension, fluid retention, or congestive heart failure. A potassium-based alkalinizer, such as potassium citrate (Urocit K), may prove more efficacious under these circumstances. Conversely, Stephen W. Leslie, MD, has found that some of his patients have very alkaline urine, which can also be irritating and result in discomfort and dysuria.

Sitz bath

Sitz baths may provide partial relief from acute exacerbations. Rather than a shallow perineal dip, a deep tub bath in water as hot as can be comfortably tolerated seems to provide better overall temporary relief and relaxation.

Spinal cord stimulation

The use of high-frequency 10 kHz spinal cord stimulation (10 kHz SCS) for treatment of chronic back and leg pain is supported by level 1 evidence and clinical experience. A review by Sayed et al found that 10 kHz SCS may also be successful for a variety of other conditions, including chronic pelvic pain.[29]

Glycosaminoglycans

Glycosaminoglycans (GAGs; eg, chondroitin sulfate, hyaluronic acid) have been studied for the therapy of various chronic pelvic pain conditions, including prostate pain syndrome/chronic prostatitis. A review found encouraging results with GAGs replenishment therapy in chronic forms of pelvic pain, but noted the need for well-powered randomized clinical trials.[30]

 

 

 

Special Concerns

Ultimately, a cure for chronic pelvic pain syndrome (CPPS) will be found by researchers who make distinctions among cases rather than by those who place all cases into a single category. Clinical investigators who are able to recognize within the conglomeration of conditions classified as CPPS a discrete subset of patients whose symptoms and findings can be proven to relate to a single, common etiologic factor will achieve meaningful success in treatment. In this way, multiple, individualized cures (as opposed to one cure) for CPPS will be progressively achieved, one subset of patients at a time.

The key to enabling this painstaking, multidirectional journey to success lies in wider encouragement and more effective funding of well-designed clinical, bench-top, and translational research projects.

Public awareness of the prevalence of CPPS, its devastating effects in terms of personal suffering, and its remarkable financial impact in terms of work-loss, hospitalizations, polypharmacy, and seemingly endless office visits needs far greater promotion. Funding for research from private and public sectors needs to be increased.

The patients who experience this condition and the physicians who care for them must have the courage to be more vocal in demanding higher priority in terms of immediate care and long-term research.

Consultations

Pain management specialist

Anesthesiologists and other experts in pain management may be able to assist in providing significant symptomatic relief. No analgesics are specifically appropriate in the treatment of prostatitis. Standard mild analgesics such as acetaminophen, aspirin, and ibuprofen are well within the purview of the urologist's (and indeed, the primary care physician's) domain of management.

Keep in mind that the patient's analgesic needs are likely to fluctuate. Often, encouraging the patient to maintain a long-term, low-level intake of a minor analgesic such as acetylsalicylic acid or acetaminophen three times daily diminishes his need for more potent analgesics. Patient and physician fear of analgesic abuse or addiction often lead to undermedication, causing unnecessary pain and suffering.

Be quick to invite consultation from specialists at an established pain management center. Clinicians at Washington University have documented the beneficial impact that a coordinated, multidisciplinary approach between the urologist and the pain management team can have on improving the quality of life for many of these patients. These patients are often dismissed too easily, and their complaints are trivialized. Symptomatic patients can be encumbered by pain as devastating as that caused by cancer, neurologic diseases, and other conditions that merit a vigorous approach to effective pain management.

Psychiatrist

Frequently, if only anecdotally, patients with CPPS have been categorized as being tense, high-strung, hypochondriacal, and even neurotic. Experiencing the daily torment of uncontrolled pelvic pain, urinary dysfunction, and social embarrassment can understandably lead to profound psychological sequelae. Many patients encounter frustrated, dismissive, and unhelpful physicians in the course of treatment, compounding their frustration, depression, and despair. A sympathetic, constructive attitude by the physician can do much to alleviate this strain.

Moreover, a mild relaxant such as diazepam (Valium), prescribed judiciously, may help the patient adjust to his condition and, at the same time, relax the spasm of the pelvic floor muscles, providing objective relief.

Prescribe psychiatric medications with caution and rarely without consultation with a psychiatrist. A psychiatrist who is particularly interested in helping patients with CPPS can be a valuable member of the treatment team that includes the primary care physician, the urologist, and the pain management experts.

Researchers in Taiwan followed 3051 adults, who had been newly diagnosed with CP/CPPS over a 3-year period. These patients were more likely to subsequently develop a depressive disorder in that time frame than were a control group without CP/CPPS who were followed for the same amount of time (hazard ratio, 1.63). The risk was particularly high for men younger than 30 years (hazard ratio, 2.50).[20]

This study serves to remind of the importance of “whole-man” evaluation and follow-up for patients with this condition. Urologists and other clinicians need to be attentive to the profound psychological impact of CP/CPPS. Coping mechanisms and medications that address the patient’s mental condition may also assist importantly in ameliorating his physical symptoms.

Avoiding a misunderstanding when recommending psychiatric counseling is important because the patient may perceive that his physician thinks that he is insane, hysterical, or delusional. Reassure the patient that his condition is real and that his suffering is not imaginary. Psychological support is appropriate in helping the patient cope more effectively with his serious, real-life problem.

Andrology specialist

An andrology specialist should be consulted for management of erectile dysfunction, if present. Specialists at Stanford University found that 92% of men with refractory CPPS reported related erectile dysfunction, including problems with decreased libido (66%), pain upon ejaculation (56%), and ejaculatory dysfunction (31%).[31] In a cross-sectional study of 8,261 Korean men, a significant correlation was found between scores on the Premature Ejaculation Diagnostic Tool and NIH-CPSI scores, which persisted after adjustment for age, metabolic syndrome status, testosterone level, and International Index of Erectile Function-5 score.[32]

Sexual dysfunction is a potentially devastating effect of CPPS, and managing it can greatly improve the patient's attitude and quality of life. An excellent review of this topic by Sadeghi-Nejad and Seftel brings attention to reports that link CPPS to sexual dysfunction.[33]

Many remedies and treatments are available, including phosphodiesterase-5 enzyme inhibitors (eg, sildenafil), vacuum devices, injection and intraurethral therapies, and penile implants; a physician would be profoundly remiss to not broach the topic and its treatment possibilities. The patient’s partner should be strongly encouraged to be involved early in the counseling and treatment process.

Physical medicine therapist and physiotherapist

Clinical researchers at Columbia University found that an important subset of patients who had been treated unsuccessfully for symptoms of chronic abacterial prostatitis for between 1.5 and more than 10 years and who were unresponsive to long-term antibiotic and alpha-blocker therapies were actually experiencing pseudodyssynergia (a contraction of the external sphincter during voiding). This condition was documented based on electromyographic and fluoroscopic findings. Patients thus identified responded to treatment with biofeedback and behavior modification in 83% of cases.[34]

Lately, authorities have appreciated that, in many cases, symptoms formerly attributed to CPPS may actually reflect pelvic floor spasm and chronic pelvic pain that is not prostatic in origin. In light of this, physiotherapists may provide an important role in helping to diagnostically distinguish and therapeutically ameliorate neuromuscular-based symptoms. For example, patients with palpable myofascial tenderness in the rectal area often chronically unable to relax their pelvic floor musculature. This dysfunction of the pelvic floor muscles (ie, levator syndrome) is objectively documentable. Moreover, significant symptomatic relief has been achieved through modulation-based therapies such as biofeedback, alpha blockers, and sacral nerve stimulation.

Six weeks of electroacupuncture therapy has been shown to produce significant pain relief. In this technique, electroacupuncture is applied at six different sites via an electrical pulse generator in order to release spasm in the pyriformis muscle while stimulating the sacral nerve.[35] A prospective, randomized, nonblinded clinical trial in 54 men with class IIIB CP-CPPS found that electroacupuncture, given twice a week for 7 weeks, was more effective than levofloxacin plus ibuprofen for improving pain, urinary symptoms, quality of life, and total NIH-CPSI scores.[36]

Growing clinical experience strongly suggests that pain syndromes labeled prostatitis may in fact reflect tension in the pelvic musculature and its associated tendons—myofascial pain. It is postulated that, in these cases, CPPS is not isolated to the prostate but is rather a neuro-inflammatory condition that releases endogenous pain-producing substances.

A study by Anderson et al suggested that pain in at least a subset of patients with chronic prostatitis (CP)/CPPS may result from a variant of fibromyalgia rather than from prostatic inflammation. Spasm in these muscles causes referred pain to the penis, prostate, or neighboring pelvic structures. For example, pressing on a trigger point in the muscles of the pelvic floor (puborectalis/pubococcygeus muscles) was found in the study to cause patients to experience penile pain.[37]

A trigger point is a hyperirritable, sensitive, or tender spot within a taut, palpable band of skeletal muscle or fascia. Ten different myofascial trigger points were identified within the pelvic region. In the Anderson study, pressing firmly on one or more of these pressure points caused the patient to experience referred pain in one or more of seven different sites: the penis, perineum, rectum, suprapubic area, testicles, groin, and/or buttocks.

It is speculated that, at least in some cases, the tenderness experienced by individuals with CP/CPPS during digital prostate examination may be due less to palpation of an inflamed prostate and more to inadvertent stimulation of myofascial trigger points in the pelvic floor musculature on which the prostate is resting. Significant pain reduction has been achieved with myofascial release therapy.[38]

Long-Term Monitoring

Patients should keep a CPPS diary that has a page for each date, divided into two columns for a voiding diary and an environmental impact record.

Voiding diary

In the voiding diary, (1) the time and approximate amount of each void and (2) the time and amount of each fluid intake are recorded. This record helps to distinguish between urinary frequency (voiding normal amounts of urine over a 24-h period but in small, frequent voids) and polyuria (voiding excessive amounts of urine each day overall).

In this light, objectively monitoring the patient's response to the advice to drink large quantities of water each day is often valuable. The general agreement is that dehydration should be avoided because good hydration contributes to overall well-being and may dilute the concentration of the urinary irritants that exacerbate symptoms of chronic pelvic pain syndrome (CPPS) type III.

On the other hand, advising a patient already seriously affected by excessive daytime and nocturnal frequency and urgency to maximally increase his intake of fluid seems counterintuitive.

While advice to drink large quantities of water might be interpreted by one patient as meaning 1-2 quarts of fluid each day, another might take it to mean 1-2 gallons. Information from a voiding diary can help to guide the patient safely between the hazards of too much and too little daily fluid intake.

Environmental impact record

In the environmental impact record, every possible incident of living, on days when symptoms flare up markedly and on days when symptoms are unusually quiescent, is detailed. All incidents of daily living are recorded, including those on the following list:

  • The type, time, and amount of food and beverage intake
  • Exercise performed or lack of activity, including bike riding, long car rides, and prolonged sitting or standing
  • Incidents of sexual stimulation and whether or not they resulted in ejaculation
  • They should also include a lack of sexual stimulation
  • Any unusual physical or emotional stress
  • Exposure to allergens, such as animals, dust, and pollen

Each day, when either a marked flare-up or an unusual abatement of symptoms occurs, the patient is encouraged to complete both columns of the diary in fullest possible detail.

Evaluation of the diary

After a series of good days and bad days have been recorded, the patient can review these recordings with the physician, looking for patterns in diet, exposure, or activity that characterize either type of day. The idea is to reduce factors associated with flare-ups and to maximize factors associated with relief.

This exercise should not be undertaken with the expectation of a cure for CPPS, but rather with the hope that clearer insight will be gained into some of the factors influencing the condition, which may provide the patient with better control over it.

 

Guidelines

Guidelines Summary

In 2015, Prostate Cancer UK released consensus guidelines for the diagnosis and management of chronic bacterial prostatitis (CBP) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). The guidelines define early-stage disease as persistent, recurrent symptoms for < 6 months in antibiotic‐naïve men. In later-stage disease, patients experience persistent, recurrent symptoms for >6 months that are refractory to initial lines of pharmacotherapy. The recommendations for evaluation include the following[1] :

  • Use of reliable instruments, such as the National Institutes of Health Chronic Prostatitis Symptom Index (NIH‐CPSI), International Prostate Symptom Score (IPSS), and UPOINT system, should be considered to assess initial symptom severity, evaluate phenotypic differences, and monitor patients' response to therapeutic intervention.
  • Patients should be screened for psychosocial symptoms (eg, anxiety or stress) using either the psychosocial yellow flag system and/or Patient Health Questionnaire–9 (PHQ‐9) and/or Generalized Anxiety Disorder–7( GAD‐7) scales.
  • Referral to a mental health specialist (eg, psychiatrist, clinical psychologist) should be considered if clinically relevant levels of psychosocial symptoms are present.
  • Other concerns or differential diagnoses, including urological cancers and infertility, should be discussed with the patient to establish a full patient history.
  • Patients should be informed of the underlying causes of CBP and CP/CPPS to help improve their understanding. This may include an explanation of basic pelvic anatomy, the chronic pain cycle, and potential routes for pain (neuropathic vs nociceptive).

The guidelines include the following recommendations for treatment of CP/CPPS[1] :

  • Consider α‐adrenergic antagonists as an initial treatment option, although there is a lack of evidence to inform best practice for the use of these agents and they have a modest treatment effect regarding total, urinary symptom, pain, and quality of life (QoL) scores. 
  • Treatment with α‐adrenergic antagonists should be considered in patients who present with significant voiding lower urinary tract symptoms (LUTS; eg, slow urinary flow, hesitancy); if no relief from voiding LUTS or other symptoms is achieved within 4–6 weeks, treatment should be stopped and a different pharmacotherapy considered. Patients should be referred to specialist care if other approaches have been exhausted.
  • Due to the adverse effect profiles, consider uroselective α‐adrenergic antagonists (eg, tamsulosin, alfuzosin, silodosin) as first‐line treatment in patients who present with voiding LUTS.
  • Antimicrobial therapy may have a moderate effect on total, urinary, pain and QoL scores and should be considered as an initial treatment option  
  • Antimicrobial therapy should be guided by bacterial cultures and sensitivities, taking into consideration any drug interactions and/or contraindications  
  • For patients with early‐stage disease, a quinolone (eg, ciprofloxacin or ofloxacin) for 4–6 weeks may be offered as first‐line therapy.
  • A repeated course of antibiotic therapy (4–6 weeks) should be offered only if a bacterial cause is confirmed or if the patient has a partial response to the first course.
  • If a bacterial cause is excluded (eg, via urine dipstick or culture) and symptoms do not improve after antibiotic therapy, a different treatment method or referral to specialist care should be considered.
  • Multimodal/combined therapy should be individualized for each patient; depending on the symptoms at presentation; possible additions to first‐line antibiotic therapy include an α‐blocker and/or a nonsteroidal anti-inflammatory drug (NSAID), an agent targeting neuropathic pain (eg, pregabalin), or a 5-α‐reductase inhibitor (predominantly for patients with coexisting LUTS and benign prostatic hyperplasia).
  • Patients whose condition is refractory to treatment should be questioned about the possibility of any past trauma (including physical, emotional, or sexual abuse)
  • A multidisciplinary team should be utilized for treatment of refractory symptoms, with pharmacotherapy, physical, and psychosocial approaches integrated into an individualized treatment plan.
  • The multidisciplinary team may include urologists, pain specialists, nurse specialists, physiotherapist, general practitioners, cognitive behavioral/psychological therapists, and sexual health specialists.
  • There is insufficient evidence to recommend surgical techniques, including radical prostatectomy, transurethral resection of the prostate (TURP), high-intensity focused ultrasound (HIFU) or prostatic massage, except in the context of a clinical trial.
  • If non‐physical causes for symptoms have been excluded, physiotherapy may be considered.
  • After referral, a full assessment (eg, symptom score scaling, examination of the pelvic floor muscles) should be completed to guide the subsequent sequence of physiotherapy treatments.

The following physiotherapy treatment options may be considered:

  • Pelvic floor re‐education
  • Local pelvic floor relaxation
  • Biofeedback
  • General relaxation
  • Deep relaxation/mindfulness
  • Trigger point release
  • Myofascial release
  • Stretches
  • Exercise for pain management
  • Transcutaneous electrical nerve stimulation (TENS)
  • Acupuncture for trigger point release and pain management
  • Bladder retraining

The guidelines also include the following recommendations for pain management[1] :

  • In patients with early‐stage disease, regular paracetamol (acetaminophen) may be offered for management of pain symptoms.
  • NSAIDs should be offered only for short‐term treatment of pain, to patients with early‐stage disease whose symptoms are suspected to be due to an inflammatory process, or those judged to be experiencing an inflammatory flare. 
  • To prevent unwanted adverse effects, NSAIDs should be stopped within 4–6 weeks of treatment initiation if they do not reduce symptoms.
  • In patients with early‐stage disease, use of opioids for pain management should be avoided.
  • If pain is considered to be neuropathic in origin, consider treatment with a gabapentinoid (eg, pregabalin or gabapentin), a tricyclic antidepressant (eg, amitriptyline, nortriptyline, trimipramine) or a selective serotonin‐noradrenaline (norepinephrine) reuptake inhibitor (eg, duloxetine).
  • Consider referral to a pain specialist when pain is severe and refractory to treatment or is significantly impairing the patient's lifestyle and ability to participate in daily activities

 

 

Medication

Medication Summary

By definition and exclusion, nonbacterial prostatitis, or chronic pelvic pain syndrome (CPPS), is without a documented bacterial origin. Antibiotics should have a very limited role in therapy for this condition. However, in desperation to do something for the patient, physicians frequently prescribe multiple courses of antibiotics, often for extraordinarily protracted periods.

Keep in mind that no antibiotic regimen has been proven to be efficacious in the treatment of chronic nonbacterial prostatitis. According to Meares, "Antibacterial agents are neither effective nor indicated in the treatment of nonbacterial prostatitis."[39, 40, 41] If Ureaplasma urealyticum or Chlamydia trachomatis infection is suggested, however, a trial treatment of antibiotics may be considered.

In bacterial prostatitis, antibiotic therapy may be guided by culture findings from the prostatic secretions, from the ejaculate, from a urethral swab, or from the spun sediment of a final voided urine specimen (VB3). Even in this scenario, choosing the antibiotic is confounded by the fact that the organisms cultured from these sources may reflect urethral contaminants rather than a true pathogen.

In an aggressive attempt to clarify the presence of bacteria in the uncontaminated prostate tissue of men with CPPS, researchers in Seattle concluded that, while bacterial colonization within the prostate is not uncommon, particularly in older men, prostatic bacteria are probably not etiologically involved in the symptoms of most men with CPPS. The investigators performed digitally guided transperineal prostate biopsies in 118 subjects with CPPS and in 59 control subjects. They found no significant difference in the rates of positive cultures (38% vs 36%).[42]

Some patients with CPPS are maintained on long-term, low-dose regimens, such as one tablet of trimethoprim-sulfamethoxazole (Septra DS) daily. In some cases, patients experience symptomatic relief while on these regimens. Whether this is a reflection of the strong placebo effect associated with treatment of this condition or the result of suppression of an undetected pathogen is purely a matter of speculation. Studies suggest that, beyond the placebo effect, certain antibiotics may actually be providing an objective anti-inflammatory and/or analgesic benefit to these patients.

In screening for a bacterial etiology, the finding of gram-positive organisms has often been dismissed as a contaminant. However, small studies have found evidence to suggest that anaerobes and gram-positive aerobes, even coagulase-negative staphylococci, may in fact be pathogens, and appropriate antibiotic therapy has proven effective in select cases.[43]

In approaching the antibiotic option, remember that no antibiotic is free of complications. Regarding a blinded trial of antibiotics for CPPS, many have commented that the antibiotics cannot hurt. As a grim reminder of the rare, but devastating, consequences attendant to the casual use of such antibiotics, the primary author consulted on the treatment of a patient who experienced life-threatening complications following liver/kidney transplantation that was necessitated by his extremely adverse reaction to a course of trimethoprim-sulfamethoxazole. Tragically, the symptoms of chronic prostatitis (CP), for which this antibiotic was prescribed, were later proven to be manifestations not of prostatitis, but of a bladder neck contracture.

It should also be kept in mind that the expense of antibiotics is not negligible, particularly when multiple prescriptions are provided for the newest, most expensive wide-spectrum antibiotics.

The Urologic Diseases in America Project, reviewing Veterans Health Administration datasets, found that men with CP/CPPS were seven times more likely to have received a fluoroquinolone than were men without this condition. An increased use of other antibiotics was also observed. Despite the evidence that antibiotics are not effective in most men with CP/CPPS, they were prescribed in 69% of men with this diagnosis, suggesting that strategies to reduce unnecessary antibiotic use in these patients are warranted.[44]

In an editorial published in the Journal of Urology, Professor Richard Berger speculated that while considerable evidence suggests that antibiotics are no more effective than placebo in the treatment of CP/CPPS, this finding may be contrary to common experience, as the success rate associated with placebo has been approximately 50%. Thus, half of these men fare better whenever they are given something. It would not be surprising if the most common cause of inappropriate antibiotic prescriptions by urologists were for CP/CPPS type III, and if it were a major contributor to fluoroquinolone antibiotic resistance.[45]

Berger observes, "Because of our inappropriate nomenclature of 'prostatitis,' (when it is neither an infection nor an inflammation) and the message given by our antibiotic treatment, many men end up thinking they have an incurable but unknown infection. Old habits are hard to change, but need to be replaced by patient education, and perhaps by physical education and pain-directed drug therapy."[46]

In a controlled, randomized investigation by the Chronic Prostatitis Collaborative Research Network-2, pregabalin (Lyrica) failed to show an advantage in relieving discomfort, as measured by the NIH Chronic Prostatitis Symptom Index. The problem was that while 47.2% of the men experienced significant (> 6-point) relief when taking pregabalin, 35.8% of the men who were taking a placebo also experienced relief. Patients taking pregabalin fared better on the McGill Pain Questionnaire. Despite these findings, clinicians still hold that pregabalin may have a role in pain relief for select CP/CPPS patients. It is important to bear in mind that use of pregabalin is not US Food and Drug Administration approved for the treatment of CP/CPPS pain.[47]

Antibiotics

Class Summary

Chronic pelvic pain syndrome (CPPS) in men should, by definition, exclude men with a proven bacteriologic etiology. Therefore, antibiotics should not be deemed appropriate for the treatment of this condition. However, most practitioners are inclined to attempt at least 1 trial of long-term antibiosis.

Clinical evidence upon reviewing the results of all available clinical trials indicates limited validation for the use of antibacterials, even in the face of chronic bacterial prostatitis. The cure rates for sterilization of prostatitic secretions, even for this more specific indication, ranged from 0-90% and correlated poorly with symptomatic responses. Limited evidence from retrospective studies suggests that quinolones (eg, ciprofloxacin [Cipro], levofloxacin [Levaquin]) may be more effective than trimethoprim-sulfamethoxazole (Bactrim, Septra).

Minocycline (Dynacin, Minocin)

Minocycline helps to treat infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible chlamydial, rickettsial, and mycoplasmal organisms.

Erythromycin (E.E.S., E-Mycin, Ery-Tab)

Erythromycin is a macrolide antibiotic with the theoretical advantage of penetrating the blood-prostate barrier, but it carries an increased incidence of gastrointestinal (GI) intolerance.

Ciprofloxacin (Cipro)

Ciprofloxacin is a fluoroquinolone with activity against Pseudomonas species, streptococci, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, and most gram-negative organisms, but no activity against anaerobes. It inhibits bacterial DNA synthesis and, consequently, growth. Continue treatment for at least 2 days (7-14 d typical) after signs and symptoms have disappeared.

Muscle Relaxants

Class Summary

Tension myalgia of the pelvic floor muscles, combined with overall stress-related tension, can be partially relieved with muscle relaxants.[39, 40, 41]

Diazepam (Valium, Diastat)

Diazepam is a benzodiazepine derivative indicated for short-term relief of anxiety and adjunctive relief of skeletal muscle spasm. It depresses all levels of the CNS (eg, limbic and reticular formation), possibly by increasing the activity of gamma-aminobutyric acid (GABA). Individualize the dosage and increase it cautiously to avoid adverse effects.

Alpha-Adrenergic Blockers

Class Summary

These agents have become a mainstay in the symptomatic treatment of chronic pelvic pain syndrome (CPPS) in men.[39, 40, 41] These agents, by relieving the secondary smooth muscle spasm within the bladder neck and prostatic urethra, afford the patient greater comfort in voiding. The dosage should be titrated progressively and administered at night to minimize the main adverse effect of orthostatic hypotension. The final dose must be individualized to meet the patient's needs.

While the antihypertensive agent has been administered to patients already taking other blood pressure medications, coordinating the addition of this medication with the primary care physician or cardiologist who is prescribing the patient's other antihypertensive medications is wise.

Again, as with other medications, such as antibiotics, remember that the use of alpha-adrenergic blockade is not approved by the US Food and Drug Administration (FDA) for the treatment of prostatodynia. One study suggested an advantage to the use of alpha blockers in combination with antibiotics over antibiotic therapy alone in the treatment of chronic bacterial prostatitis.[45]

Doxazosin (Cardura)

Quinazoline compounds counteract alpha1-induced adrenergic contractions of the bladder neck, facilitating urinary flow in the presence of benign prostatic hyperplasia (BPH).

Terazosin (Hytrin)

Terazosin is a quinazoline compound that counteracts alpha1-induced adrenergic contractions of the bladder neck, facilitating urinary flow in presence of BPH. Reporting at the annual convention of the American Urological Association, researchers confirmed a significant, albeit limited, value for alpha1-blockers in the management of CPPS. Patients with CPPS treated with terazosin showed a 56% improvement in their NIH-CPSI scores; however, placebo controls showed a 36% response rate.

In a parallel report from Finland, using the selective alpha-blocker alfuzosin, modest improvement again occurred. After 6 months, 19 patients on alfuzosin showed significant reduction in pain scores but not in voiding or quality-of-life scores. This finding seems counterintuitive in that one would expect an alpha blocker to have its most dramatic effect on voiding performance. Moreover, unlike BPH treatment, in which a response to alpha blockers is prompt, the symptomatic response in patients with CPPS can take 6 months or longer to mature.

These studies raise the question of whether the expense and nuisance of these long-term medications are warranted for this modest response, which is in close competition with the placebo effect.

Tamsulosin (Flomax)

Tamsulosin is an alpha-adrenergic blocker that specifically targets A1 receptors. It has the advantage of causing relatively less orthostatic hypotension and requires no gradual up-titration from the initial introductory dosage. On the other hand, the rate of ejaculatory dysfunction is higher with this medication (8.4-18.1%).

 

Questions & Answers

Overview

What is chronic pelvic pain syndrome (CPPS)?

What causes chronic pelvic pain syndrome (CPPS)?

Which fastidious bacteria cause chronic pelvic pain syndrome (CPPS)?

What is the role of P acnes in the etiology of chronic pelvic pain syndrome (CPPS)?

What is the role of E coli in the etiology of chronic pelvic pain syndrome (CPPS)?

What are the neurologic causes of chronic pelvic pain syndrome (CPPS)?

What are the immunologic causes of chronic pelvic pain syndrome (CPPS)?

What is the prevalence of chronic pelvic pain syndrome (CPPS)?

Where are patient education resources about chronic pelvic pain syndrome (CPPS) found?

Presentation

Which clinical history findings are characteristic of chronic pelvic pain syndrome (CPPS)?

Which physical findings are characteristic of chronic pelvic pain syndrome (CPPS)?

DDX

Which conditions are included in the differential diagnoses of chronic pelvic pain syndrome (CPPS)?

How is chronic pelvic pain syndrome (CPPS) differentiated from interstitial cystitis?

How is chronic pelvic pain syndrome (CPPS) differentiated from chronic urethritis?

How is chronic pelvic pain syndrome (CPPS) differentiated from prostate cancer?

What are the differential diagnoses for Chronic Pelvic Pain in Men?

Workup

How is chronic pelvic pain syndrome (CPPS) diagnosed?

What is the role of imaging studies in the workup of chronic pelvic pain syndrome (CPPS)?

What is the role of a formal flow rate study in the workup of chronic pelvic pain syndrome (CPPS)?

What is the role of urinalysis and culture in the workup of chronic pelvic pain syndrome (CPPS)?

What is the role of diagnostic prostatic massage in the workup of chronic pelvic pain syndrome (CPPS)?

What is the role of PSA testing in the workup of chronic pelvic pain syndrome (CPPS)?

What is the role of urine cytology in the workup of chronic pelvic pain syndrome (CPPS)?

What is the role of videourodynamic evaluation in the workup of chronic pelvic pain syndrome (CPPS)?

What is the role of cystoscopy in the workup of chronic pelvic pain syndrome (CPPS)?

What is the role of EMG in the workup of chronic pelvic pain syndrome (CPPS)?

Treatment

What are the challenges of chronic pelvic pain syndrome (CPPS) treatment?

How is chronic pelvic pain syndrome (CPPS) treated?

How is chronic pelvic pain syndrome (CPPS) prevented?

What is the UPOINT system for categorizing chronic pelvic pain syndrome (CPPS)?

What is the role of prostatic massage in the treatment of chronic pelvic pain syndrome (CPPS)?

What is the role of therapeutic ejaculation in the treatment of chronic pelvic pain syndrome (CPPS)?

What is the role of TURP in the treatment of chronic pelvic pain syndrome (CPPS)?

What is the role of myofascial release therapy in the treatment of chronic pelvic pain syndrome (CPPS)?

Which dietary modifications are used in the treatment of chronic pelvic pain syndrome (CPPS)?

What is the role of sitz baths in the treatment of chronic pelvic pain syndrome (CPPS)?

What is the long-term outlook for new treatment approaches to chronic pelvic pain syndrome (CPPS)?

Which specialist consultations are beneficial for pain management in chronic pelvic pain syndrome (CPPS)?

What are the benefits of a psychiatric consultation in patients with chronic pelvic pain syndrome (CPPS)?

What are the benefits of a consultation with an andrology specialist in patients with chronic pelvic pain syndrome (CPPS)?

What is the role of physiotherapy in the treatment of chronic pelvic pain syndrome (CPPS)?

What is included in the long-term monitoring of chronic pelvic pain syndrome (CPPS)?

What is the role of a voiding diary in the long-term monitoring of chronic pelvic pain syndrome (CPPS)?

What is the role of an environmental impact record in the long-term monitoring of chronic pelvic pain syndrome (CPPS)?

How is a voiding diary evaluated during the treatment of chronic pelvic pain syndrome (CPPS)?

Guidelines

What are the Prostate Cancer UK guidelines on the diagnosis and treatment of chronic pelvic pain syndrome (CPPS)?

Medications

What is the role of medications in the treatment of chronic pelvic pain syndrome (CPPS)?

Which medications in the drug class Alpha-Adrenergic Blockers are used in the treatment of Chronic Pelvic Pain in Men?

Which medications in the drug class Muscle Relaxants are used in the treatment of Chronic Pelvic Pain in Men?

Which medications in the drug class Antibiotics are used in the treatment of Chronic Pelvic Pain in Men?