Chronic Pelvic Pain Syndrome and Prostatodynia and Prostatitis

Synonyms and related keywords:

prostatodynia, prostatalgia, nonbacterial prostatitis, prostatitis, chronic pelvic pain syndrome, CPPS, enlarged prostate, swollen prostate, chronic prostatitis, prostate pain, chronic voiding symptoms, irritative voiding, obstructive voiding, erectile dysfunction, ED, Ureaplasma urealyticum, U urealyticum, Chlamydia trachomatis, C trachomatis, myofascial pain syndrome

INTRODUCTION

Section 2 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workp
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

The term prostatodynia, or chronic pelvic pain syndrome (CPPS), is used to designate unexplained pelvic pain in men; this pain is associated with irritative voiding symptoms and/or pain located 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 WBCs or bacteria seen on Gram stain and culture of expressed prostatic secretions (EPS) may be found.

The use of the term prostatodynia is not encouraged in current practice. This term 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.

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. However, this number may vary widely within the same specimen and even more so from sample to sample taken from the same patient. Furthermore, asymptomatic control patients devoid of any evidence of pelvic pathology have also been found to have a significant number of WBCs in their prostatic secretions. At present, the distinction seems to provide no meaningful differential with respect to either etiology or treatment options.

Pathophysiology

Pontari and Ruggieri's comprehensive 2004 update reviews the numerous pathophysiologic mechanisms implicated as the potential etiology of CPPS. After surveying all of the relevant articles on this topic published from 1966-2003, these researchers reached the following conclusions:

• The etiology (or etiologies) of CPPS remains unknown.
• 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. Histological signs of inflammation were found in only one third of all patients diagnosed with CPPS who underwent prostatic biopsy, further suggesting an extraprostatic etiology for CPPS. Perhaps CPPS—so-called chronic prostatitis (CP)—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 act as 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, the abnormal tendency of the body to react against itself, 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 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 causation 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, which, in turn, leads 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. More recent data, however, suggest 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. Recent data suggest that gram-positive bacteria, which have traditionally been dismissed as normal florae in prostatic fluid cultures, may not be so normal in men with CPPS. Normal defense mechanisms allow healthy men to render these bacteria harmless as mere microbial "hitchhikers." However, these defense mechanisms may be defective in men with CPPS. This theory helps 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 that "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." Clearly, the final answer (or answers) is not yet determined. Opportunities abound for clinical and basic science research in this area.

Frequency

United States

CP is the most common urological diagnosis in men older than 50 years and is the third most common diagnosis in men younger than 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 or prostatodynia, otherwise known as CPPS in the male.

Age

CP most commonly affects men older than 50 years. It is only slightly less common in men younger than 50 years.

CLINICAL

Section 3 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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 US National Institutes of Health (NIH) collaborative panel has proposed the Chronic Prostatitis Symptom Index (NIH-CPSI). This index is calculated using a series of 9 questions that contain 21 items used to assess patient history in a standardized and quantifiable format.
• • Pain symptoms (4 questions)
  • • In the past week, have you experienced any pain (1) between your rectum and testicles, (2) in the testicles, (3) in the tip of the penis, or (4) below your waist?
    • In the past week, have you experienced pain or burning upon urination or pain or discomfort during or after sexual intercourse?
    • How often have you had pain in any of the above areas over the last week?
    • Over the last week, which number (1-10) best describes your average pain or discomfort on the days that you had it?
  • Urinary symptoms (2 questions)
  • • Over the last week, how often have you had the sensation of not emptying your bladder completely after you finished urinating?
    • Over the last week, how often have you had to urinate again less than 2 hours after you finished urinating?
  • Impact of symptoms (2 questions)
  • • Over the last week, how much have your symptoms kept you from doing the kinds of things you would usually do?
    • Over the last week, how much did you think about your symptoms?
  • Quality of life: If you were to spend the rest of your life with your symptoms just the way they have been during the last week, how would you feel about that?
• The NIH describes 4 categories of prostatitis, as follows:
• • Type I - Acute bacterial prostatitis
  • Type II - Chronic bacterial prostatitis 
  • Type III - Chronic abacterial prostatitis, ie, chronic pelvic pain syndrome (CPPS) categorized as either type IIIa (inflammatory CPPS) or type IIIb (noninflammatory CPPS) 
  • Type IV - Asymptomatic inflammatory prostatitis

Physical

• No finding 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.

Causes

• Bacteria
• • An informative review of the possible role for fastidious bacteria (ie, bacteria that cannot be isolated on standard culture media) in the development of chronic prostatitis (CP)/CPPS has recently been presented by a leader in this field, Professor John N. Krieger at the University of Washington. Among the fastidious organisms that have been implicated are Chlamydia trachomatis, the genital mycoplasmas (ie, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium), a protozoan (ie, Trichomonas vaginalis), Neisseria gonorrhoeae, genital tract viruses (eg, herpes simplex virus types 1 and 2, cytomegalovirus), fungi, anaerobic bacteria, and gram-positive bacteria.
  • Only 10 (8%) of 135 patients with CP/CPPS in this series tested positive for fastidious organisms. However, in another series, 79 (47%) of 170 specimens from patients with CP/CPPS exhibited gene sequencing (16S rDNA) positive for the presence of microbes, while only 21 (20%) of 117 control specimens from patients undergoing radical prostatectomy were positive (P <.01). These observations support a potential role for uncommon organisms in CP/CPPS.
• Bacteriologic breakthroughs
• • Propionibacterium acnes
  • • Intriguing findings from collaborating investigators in Australia and California now suggest that persistent microbial infection with 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.The presence of this organism, P acnes, could be detected only via sophisticated gene-sequencing and polymerase chain reaction technology. P acnes could not be identified using routine histology, Gram stain, or routine culture techniques.
    • 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 both CP and prostate cancer.
  • Escherichia coli
  • • E 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.
    • 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, one of the quinolones), 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 prevent the inflammation from progressing into the chronic phase of bacterial or abacterial prostatitis.
• Neuropathy
• • Findings of spastic hyperactivity in the absence of a definable underlying neuropathy from videourodynamic studies 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 CPPS/CP. 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.

 

DIFFERENTIALS

Section 4 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Acute Bacterial Prostatitis and Prostatic Abscess
Anal Fissure
Bladder Cancer
Carcinoma In Situ of the Urinary Bladder
Chronic Pelvic Pain
Colovesical Fistula
Cystitis, Nonbcterial
Fistula-in-Ano
Gonococcal Infections
Hemorrhoids
Infertility
Infertility, Male
Inflammatory Bowel Disease
Nonbacterial Prostatitis
Prostate Cancer: Biology, Diagnosis, Pathology, Staging, and Natural History
Tuberculosis
Tuberculosis of the Genitourinary System
Urethral Cancer
Urethral Diverticula
Urethral Diverticulum
Urethritis

Other Problems to be Considered

Tuberculous prostatitis
Sexually transmitted diseases
Congenital or acquired abnormalities of the urethra
Prostatic cyst
Prostatic abscess
Seminal vesiculitis
Myofascial pain syndrome
Reiter syndrome
Pelvic joint dysfunction
Coccydynia

These many differential diagnoses—and this list is by no means complete—reveal the conundrum of diagnosing prostatodynia. 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.

An archetypical example would be differentiating between prostatodynia and interstitial cystitis in the male. A detailed review of the diagnosis of interstitial cystitis is presented thoroughly in . The distinction between prostatodynia and interstitial cystitis is pInterstitial Cystitisarticularly challenging because both conditions are diagnoses of exclusion, ie, 2 separate "wastebasket" diagnoses. No diagnostic test can be used to definitively establish or to exclude the diagnosis of 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 hydrodistension to search for indicative signs is prudent and cost effective. However, the pathognomonic Hunner ulcer 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 3 reports disparaged the utility of the once heavily promoted potassium sensitivity test. Conversely, Parsons and Albo (2002), who are leaders in the field of interstitial cystitis, 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.

In 2004, urologic specialists at the University of Oklahoma reviewed a series of 92 men diagnosed with interstitial cystitis. This condition had been diagnosed 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 hydrodistension. These researchers caution that the symptoms of interstitial cystitis closely parallel those of CP/chronic pelvic pain syndrome (CPPS). (For further information, see Interstitial Cystitis.)

Most of the patients with interstitial cystitis in this series were referred for urological evaluation with an initial diagnosis of CP (54%) or of benign prostatic hyperplasia (23%). Their 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 both 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 2 of these patients. (As a side note, these researchers observed an unusually high prevalence of interstitial cystitis among Native American [Cherokee] men.)

The point at which the physician empirically recommends (for a given patient with prostatodynia) 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 (see Interstitial Cystitis). 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.

The distinction between chronic urethritis and CP/CPPS can prove problematic. This issue was discussed in a 2004 review from the University of Washington in Seattle. Of the 7 symptoms evaluated in the NIH Chronic Prostatitis Symptom Index, 3 symptoms are common to both populations: penile pain, urinary frequency, and dysuria. The remaining 4 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. For further information on NGU, see Urethritis.

Most importantly, 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. See  Prostate Hyperplasia, Benign. 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 me 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 prostatodynia 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 reveals 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 both for cancer and for prostatic inflammation. The researchers do not recommend any change in current recommendations, pending confirmatory studies. Meanwhile, patients with CPPS should adhere strictly to standard recommendations for prostate cancer screening.

WORKUP

Section 5 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• 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 WBCs in the expressed prostatic secretions (EPS) and/or bacteria on Gram stain and/or a heavy, nearly pure growth of a known bacterial pathogen on culture indicates 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 NIH 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, 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.
  • Stamey recommended the 3-glass urinalysis method, and, while this approach is widely taught, it is much less widely practiced by clinical urologists today. See Prostatitis, Bacterial for a detailed description of this examination. Nickel suggests that a simplified premassage and postmassage test may prove more efficacious.
• Prostate-specific antigen
• • The prostate-specific antigen (PSA) level is often elevated in men with acute bacterial prostatitis and may also be modestly elevated in those with CP/CPPS.
  • PSA testing in men with CPPS symptoms may be helpful in distinguishing between chronic bacterial prostatitis (ie, elevated PSA value) and prostatodynia (ie, PSA value within reference range); however, this theory has yet to be tested in a well-controlled clinical trial.
  • Testing this theory presents problems because researchers would have to counsel large numbers of men who are younger than 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.
• Urinary cytology: Voided urine cytologies, while not routine, should be readily considered whenever the index of suspicion is at all elevated—for instance, 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.

Imaging Studies

• Because no diagnostic finding has proven definitive, all imaging studies (eg, kidneys, ureters, and bladder radiography; intravenous pyelography; videocystourethrography; CT scanning; 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 radiographic procedures that are appropriate to that specific patient's problem.

Procedures

• Prostatic massage (diagnostic) and 3-glass urinalysis
• • Massaging the prostate produces EPS.
  • The finding of high colony counts of bacterial pathogens and/or a significant excess of WBCs suggests the presence of a treatable infectious agent, particularly if these findings can be reproduced after a second massage.
  • 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 patients 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.
• Videourodynamics
• • Videourodynamic evaluation often reveals evidence of a spastic dysfunction of the bladder neck and prostatic urethra.
  • Beyond helping detect occult neuropathies, urodynamic evaluation of patients with 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.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.
  • 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.
• 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.
• 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 several advantages, as follows:
  • • As a rule, patients with CPPS tend to be hypersensitive with a low pain tolerance. When the patient is unable to cooperate fully, endoscopic inspection is compromised.
    • General or regional anesthesia allows for more comfortable performance of cold-mucosal cup biopsies to rule out carcinoma in situ and for hydrodistension of the bladder to rule out interstitial cystitis.
    • Minor pathology, such as an annular stricture of the urethra or a prostatic polyp, can be treated at the same time.
• Anal sphincter electromyography and/or sphincter function profiles (microtip catheter)
• • With these studies, 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.

TREATMENT

Section 6 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Treating a patient with chronic pelvic pain syndrome (CPPS) challenges even the most compassionate physician. The patient is often understandably tense, wary, and defensive. Most patients 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.

• Initial points to address
• • CPPS is a well-established condition notorious for the pain and disability it causes.
  • CPPS is 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 make this condition more bearable. Over time, this condition may improve or stabilize on its own.
  • Because 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.
  • Many medications and other forms of treatment can help 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; the problem is not imagined. 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.
  • Reassure the patient that CPPS is a legitimate condition, and, more importantly, it is not cancer. This is not a life-threatening condition, it is not a venereal disease, and it is not contagious. Explain that the patient did not acquire this condition from someone else, nor will he pass it on to anyone.
  • Remind the patient that he is not alone. 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 regularly 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.
• Prostatic massage (therapeutic)
• • 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 prostate 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 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.
  • Many patients enjoy informing their partners that the doctor prescribed frequent sex as therapy, which is notable because opportunities for amusement are few when dealing with this issue.
  • 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 chaste while on prolonged business trips is apt to experience a flare-up both 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 sensitively that this activity is objectionable to some patients' moral and religious standards.

Surgical Care

Severely disabling CPPS has been teated with transurethral resection of the prostate (TURP) and even radical prostatectomy.

• Transurethral resection of the prostate
• • A widely held opinion among urologists is that TURP should be reserved for patients who have experienced extreme, persistent symptoms over a protracted period, with no relief from nonoperative interventions.
  • Reserve TURP as a rarely used approach of last resort, offered only by experienced resectionists and, even then, with the clear understanding that symptomatic relief is not guaranteed.
  • Indeed, symptoms might even worsen and might 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.
• Radical prostatectomy
• • This is an extreme measure.
  • Consider this treatment only in the most desperate of cases, if at all.

Consultations

• Pain management specialist
• • Anesthesiologists and other experts in pain management may be able to assist with providing significant symptomatic relief.
  • No analgesics are specifically appropriate in the treatment of prostatitis. Standard mild analgesics such as acetaminophen (Tylenol), 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 3 times a day diminishes his need for more potent analgesics.
  • Both 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 (see Medical Care).
  • 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 these patients can be a valuable member of the treatment team that includes the primary care physician, the urologist, and the pain management experts.
  • 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%).
    • While erectile dysfunction and its remedies are discussed in detail in Erectile Dysfunction, remember that managing this potentially devastating effect of CPPS 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.
  • Many remedies and treatments are available, including 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 counseling and treatment process.
• Physical medicine therapist and physiotherapist
• • Lately, authorities have appreciated that, in many cases, the symptoms formerly attributed to prostatodynia 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 to therapeutically ameliorate neuromuscularly based symptomatologies. 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.
  • Clinical researchers at Columbia University have found that an important subset of patients who had been treated unsuccessfully for symptoms of chronic abacterial prostatitis for 1.5 years to 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 electromyography and fluoroscopy findings. Patients thus identified responded to treatment with biofeedback and behavior modification in 83% of cases.
  • More recently, men with refractory CPPS were treated at Stanford University with one month or more of trigger point release/paradoxical relaxation training, in order to release trigger points in their pelvic floor musculature. Clinical success – markedly or moderately improved symptoms – was achieved in 70% of the patients.
  • The presence of documented inflammation of the prostate and urethra does not exclude the presence of neuromuscular spasm of the pelvic floor. Whether the spasm comes first, resulting from dysfunctional voiding in subsequent urinary infections, or the infection comes first, triggering a chronic cycle of pain and pelvic spasm, is a "chicken-or-egg" conundrum (ie, deciding which came first is virtually impossible). In either case, both the infection and the spasm must be treated concurrently to achieve long-term relief in these difficult cases.
  • While the urologist is best suited to address the prostatic inflammation, coordination of care with an interested physiotherapist for the management of biofeedback and nerve-root stimulation may prove worthwhile.

Diet

• The influence of diet on this condition varies.
• Traditionally, these 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 reduce nighttime symptoms. However, caution patients regarding the risk of an excessive sodium load with higher oral intakes, especially in those 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.

Activity

• 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.

MEDICATION

Section 7 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Keep in mind that no antibiotic regimen has been proven efficacious in the treatment of chronic nonbacterial prostatitis. According to E.M. Meares, "Antibacterial agents are neither effective nor indicated in the treatment of nonbacterial prostatitis." If U urealyticum or C trachomatis infection is suggested, a trial treatment of antibiotics may be considered.

In bacterial prostatitis, antibiotic therapy might be guided by culture findings from the prostatic secretions, from the ejaculate, from a urethral swab, or from the spun sediment of a 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 a recent aggressive attempt to clarify the presence of bacteria in the uncontaminated prostate tissue of men with chronic pelvic pain syndrome (CPPS), researchers in Seattle performed digitally guided transperineal prostate biopsies in 118 subjects with CPPS and in 59 control subjects. They found no difference in the rates of positive cultures (38% vs 36%) and concluded that, while the prostatic colonization of bacteria within the prostate is not uncommon, particularly in older men, prostatic bacteria are probably not etiologically involved in the symptoms in most men with CPPS.

Abacterial prostatitis or prostatodynia is, by definition and by exclusion, 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, multiple courses of antibiotics are frequently prescribed, often for extraordinarily protracted periods.

Some patients are maintained on long-term, low-dose regimens, such as 1 capsule of trimethoprim-sulfamethoxazole (Septra DS) daily, and some 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. Recent 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.

In approaching the antibiotic option, remember that no antibiotic is free of complications. Regarding a blinded trial of antibiotics for prostatodynia, many comment 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 is currently consulting on the treatment of a patient who is experiencing 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 of a bladder neck contracture rather than prostatitis.

The expense of these medications is not negligible, particularly when multiple prescriptions are provided for the newest, most expensive, wide-spectrum antibiotics.

Drug Category: Antibiotics

Prostatodynia (CPPS in men), by definition, should 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 one 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). However, in the absence of a well-documented bacteriologic indication, this recommendation must be weighed against the significant cost differential between these 2options.

Drug Name	Minocycline (Dynacin, Minocin)
Description	Helps treat infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible chlamydial, rickettsial, and mycoplasmal organisms.
Adult Dose	100 mg PO bid ac for 14 d
Pediatric Dose	<8 years: Not recommended >8 years: 4 mg/kg PO initially, followed with 2 mg/kg q12h
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Bioavailability decreases with antacids that contain aluminum, calcium, magnesium, iron, or bismuth subsalicylate; in women, can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider determining drug serum level in prolonged therapy; tetracycline use during tooth development (last half of pregnancy through 8 y) can cause permanent discoloration of teeth; Fanconi-like syndrome may occur with outdated tetracyclines

Drug Name	Erythromycin (E.E.S., E-Mycin, Ery-Tab)
Description	Macrolide antibiotic with theoretical advantage of penetrating blood-prostate barrier, but carries increased incidence of GI intolerance.
Adult Dose	500 mg PO qid pc for 14 d
Pediatric Dose	30-50 mg/kg/d (15-25 mg/lb/d) PO divided q6-8h; double dose for severe infection
Contraindications	Documented hypersensitivity; hepatic impairment; anuria
Interactions	Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Caution in liver disease; estolate formulation may cause cholestatic jaundice; adverse GI effects are common (administer doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occurs

Drug Name	Ciprofloxacin (Cipro)
Description	Fluoroquinolone with activity against Pseudomonas species, streptococci, MRSA, Staphylococcus epidermidis, and most gram-negative organisms, but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth. Trovafloxacin (Trovan) overcomes many of these limitations. Continue treatment for at least 2 d (7-14 d typical) after signs and symptoms have disappeared.
Adult Dose	250-500 mg PO bid for 7-14 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	In prolonged therapy, periodically evaluate organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

Drug Category: Muscle relaxants

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

Drug Name	Diazepam (Valium)
Description	Benzodiazepine derivative indicated for short-term relief of anxiety and adjunctive relief of skeletal muscle spasm. Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. Individualize dosage and increase cautiously to avoid adverse effects.
Adult Dose	2.5-5 mg PO; 2-4 dose/d prn
Pediatric Dose	0.1-0.8 mg/kg/d PO divided tid/qid
Contraindications	Documented hypersensitivity; acute narrow-angle glaucoma; severe or latent depression
Interactions	Increases toxicity of benzodiazepines in CNS with coadministration of phenothiazines, barbiturates, alcohols, and MAOIs; cisapride can significantly increase toxicity
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity)

Drug Category: Alpha-adrenergic blockers

These agents have become a mainstay in the symptomatic treatment of this condition.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 for the treatment of prostatodynia. One study has suggested an advantage for alpha-blockers in combination with antibiotics over antibiotic therapy alone in the treatment of chronic bacterial prostatitis.

Drug Name	Doxazosin (Cardura)
Description	Quinazoline compounds counteract alpha1-induced adrenergic contractions of the bladder neck, facilitating urinary flow in the presence of BPH.
Adult Dose	1 mg PO qhs initially, slowly titrate dose upward to point of maximum benefit; not to exceed 8 mg qhs
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Effects decrease with coadministration of NSAIDs; effects increase with coadministration of diuretics and antihypertensive medications
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Most troublesome adverse effect is orthostatic hypotension; edema of lower extremities, dizziness, fatigue, and dyspnea may occur; caution in patients using antihypertensive medications

Drug Name	Terazosin (Hytrin)
Description	Quinazoline compound that counteracts alpha1-induced adrenergic contractions of bladder neck, facilitating urinary flow in presence of BPH. Reporting at the annual convention of the American Urological Association, researchers have confirmed a significant, albeit limited, value for alpha1-blockers in the management of this condition. 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 mo, 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 could take 6 mo 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 (Schaeffer, 2003).
Adult Dose	1 mg PO qhs initially; slowly titrate dose upward to effect; not to exceed 10 mg qhs
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Effects decrease with coadministration of NSAIDs; effects increase with coadministration of diuretics and antihypertensive medications
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Most troublesome adverse effect is orthostatic hypotension; edema of lower extremities, dizziness, fatigue, and dyspnea may occur

Drug Name	Tamsulosin (Flomax)
Description	An alpha-adrenergic blocker that specifically targets A1 receptors. Has advantage of causing relatively less orthostatic hypotension and requires no gradual up-titration from initial introductory dosage. On the other hand, rate of ejaculatory dysfunction is higher with this medication (8.4-18.1%).
Adult Dose	0.4-0.8 mg PO qhs
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Cimetidine may significantly increase plasma concentrations; may increase toxicity of warfarin
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Not for use as antihypertensive drug; may cause orthostasis; avoid situations that may result in injuries if syncope occurs; rule out carcinoma or cancer before initiating treatment

 

FOLLOW-UP

Section 8 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Patients should keep a prostatodynia diary that has a page for each date, divided into 2 columns for a voiding diary and an environmental impact record.
• • 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 distinguish between urinary frequency (voiding normal amounts of urine over a 24-h period but in small, frequent voids) versus 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 the same advice might be interpreted by one patient as meaning 1-2 qt of fluid each day, another might take it to mean 1-2 gal. Information from a voiding diary can help guide the patient safely between the Charybdis and Scylla (ie, two inevitable dangers) of too much and too little daily fluid intake.
  • In the environmental impact record, every possible incident of living, both on those days when symptoms flare up markedly and on days when symptoms are unusually quiescent, is detailed. All incidents of daily living are recorded, including but limited to, items on the following list.
  • • Patients should record the type, time, and amount of food and beverage intake.
    • Patients should chart exercise performed or lack of activity, including bike riding, long car rides, and prolonged sitting or standing.
    • They should include incidents of sexual stimulation and whether or not they resulted in ejaculation.
    • They should also include a lack of sexual stimulation.
    • Patients should record any unusual physical or emotional stress.
    • Exposure to allergens such as animals, dust, or pollen can also be charted.
• 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.
• 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, but rather, with the hope that clearer insight might be gained into some of the factors influencing the condition, which may provide the patient better control over this condition.

Deterrence/Prevention

• Until the etiology of this condition is known, no specific preventative strategy is available.
• In some cases, this condition may be caused by the sequela of sexually transmitted disease, and, if so, 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.

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 excellent patient education resources, visit eMedicine's Men's Health Center, Prostate Health Center, Cancer and Tumors Center, and Kidneys and Urinary System Center. Also, see eMedicine's patient education articles Prostate Infections, Erectile Dysfunction, Bladder Cancer, and Bladder Control Problems.

MISCELLANEOUS

Section 9 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Referencs

Medical/Legal Pitfalls

• Medicolegal pitfalls mainly concern the failure to recognize a life-threatening condition, ie, misdiagnosing it as chronic prostatitis (CP) or prostatodynia. Chronic pelvic pain syndrome (CPPS) in the male patient is a diagnosis of exclusion. 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. The diagnosis of these and other related conditions is discussed in detail in their respective articles. For example, see the following:
• • Bladder Cancer
  • Carcinoma In Situ of the Urinary Bladder
  • Prostate Cancer: Biology, Diagnosis, Pathology, Staging, And Natural History
  • Pyonephrosis
  • Urinary Tract Obstruction

• 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, eg, thorough physical examination with digital rectal examination of the prostate, PSA measurement, urine culture and cytology, renal and/or bladder ultrasonography or intravenous pyelography, should be judiciously undertaken.

Special Concerns

• Prostatodynia, now termed CPPS in the male, is not a syndrome; it is not a discrete, narrowly defined constellation of consistent symptoms and objective findings ultimately traceable to a single, known etiology.
• CPPS in the male is a catch-all category of convenience into which physicians arbitrarily group the heterogeneous admixture of male patients who meet the following 3 criteria:
• • Physicians can find no objective explanation for patients' multivariate, long-standing symptoms.
  • A significant number of patient symptoms relate to anatomical structures located within an arbitrary radius of the prostate gland (somewhere below the umbilicus and above the mid thigh).
  • Physicians can offer no satisfactory treatment, let alone a cure, for patient symptoms.
• Ultimately, a cure for CPPS will be found by those who make distinctions among cases rather than those who place all cases into one category.
• • Clinical investigators who are able to recognize within this hapless conglomeration 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.
  • Identification of that factor and development of an effective remedy will provide a cure for that particular subset of patients with CPPS.
  • In this way, multiple, individualized cures (as opposed to one cure) for CPPS will be achieved progressively for 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 this condition; 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 both 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.