1. health and fitness
2. disease

Complications of Chronic Prostatitis
Satya Srini Vasan
Current Bladder Dysfunction Reports
ISSN 1931-7212
Volume 7
Number 2
Curr Bladder Dysfunct Rep (2012)
7:141-149
DOI 10.1007/s11884-012-0132-0
1 23
Your article is protected by copyright and
all rights are held exclusively by Springer
Science+Business Media, LLC. This e-offprint
is for personal use only and shall not be selfarchived in electronic repositories. If you
wish to self-archive your work, please use the
accepted author’s version for posting to your
own website or your institution’s repository.
You may further deposit the accepted author’s
version on a funder’s repository at a funder’s
request, provided it is not made publicly
available until 12 months after publication.
1 23
Author's personal copy
Curr Bladder Dysfunct Rep (2012) 7:141–149
DOI 10.1007/s11884-012-0132-0
INFECTIOUS BLADDER DYSFUNCTION (MS MOURAD, SECTION EDITOR)
Complications of Chronic Prostatitis
Satya Srini Vasan
Published online: 5 April 2012
# Springer Science+Business Media, LLC 2012
Abstract Chronic prostatitis (CP) is a pelvic condition in
men that needs to be distinguished from other forms of
prostatitis, such as acute and chronic bacterial prostatitis.
CP is characterized by pelvic or perineal pain lasting longer
than 3 months without evidence of urinary tract infection.
Symptoms may wax and wane and pain may radiate to the
back and perineum, causing discomfort while sitting. Dysuria, frequency, urgency, arthralgia, myalgia, unexplained
fatigue, abdominal pain, and burning sensation in the penis
may be present. Post-ejaculatory pain, mediated by nerves
and muscles, is a hallmark of the condition and serves to
distinguish CP/chronic pelvic pain syndrome (CPPS)
patients from men with benign prostatic hyperplasia and
healthy men. Some patients report low libido, sexual dysfunction, and erectile difficulties. The symptoms of CP/
CPPS appear to result from interplay between psychological
factors and dysfunction in the immune, neurological, and
endocrine systems. Some researchers have suggested that
CPPS is a form of painful bladder syndrome/interstitial
cystitis (PBS/IC). Therapies shown to be effective in treating IC/PBS (eg, quercetin) have shown some efficacy in CP/
CPPS. Recent research has focused on genomic and proteomic aspects of the related conditions. There are no definitive
diagnostic tests for CP/CPPS. This is a poorly understood
disorder, even though it accounts for 90% to 95% of prostatitis diagnoses. Its peak incidence is in men 35 to 45 years
old. In 2007, the National Institute of Diabetes and Digestive and Kidney Diseases began using the umbrella term
urologic chronic pelvic pain syndromes to refer to pain
S. S. Vasan (*)
Ankur Health Care Private Limited; Manipal Andrology
and Reproductive Services (MARS),
Bangalore, India
e-mail: [email protected]
syndromes associated with the bladder (eg, IC/PBS) and
prostate gland (eg, CP/CPPS). The prognosis for CP/CPPS
has improved greatly with the advent of multimodal treatment, including phytotherapy, pelvic nerve myofascial trigger point release, anxiety control, and chronic pain therapy.
Keywords Chronic prostatitis . Complications . Treatment .
Bladder dysfunction . Chronic pelvic pain syndrome .
Management . Diagnosis . PSA . Bacterial prostatitis .
Interstitial cystitis . Chronic urethritis . Cancer . Painful
bladder syndrome . CP/CPPS . Ejaculatory pain
Introduction
Prostatitis, an inflammatory condition of the prostate formerly known as prostatodynia, has been classified by the
National Institutes of Health (NIH) into four categories [1]:
&
&
&
&
Category 1: acute bacterial prostatitis
Category 2: chronic bacterial prostatitis
Category 3: chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CP/CPPS)
Category 4: asymptomatic inflammatory prostatitis.
Acute bacterial prostatitis is characterized by pain in the
pelvic area and during ejaculation. Chronic bacterial prostatitis is due to chronicity of bacterial infection with mild,
moderate, or severe symptoms, which is episodic. CP/CPPS
is a term used to designate unexplained chronic pelvic pain
in men. These men present with or without irritative voiding
symptoms and pain located in the groin, genitalia, or perineum without bacteriuria or pyuria. Additionally, these men
can present with recurrent urinary tract infection (UTI),
ejaculatory pain, and erectile dysfunction. Asymptomatic
inflammatory prostatitis is a condition in which there is
Author's personal copy
142
Curr Bladder Dysfunct Rep (2012) 7:141–149
inflammation of the prostate with elevation of prostatespecific antigen (PSA) and an inflamed prostate, but no
symptoms of prostatitis. CP/CPPS is a clinical syndrome
defined primarily on the basis of urologic symptoms and/or
pain or discomfort in the pelvic region. Despite the use of
the term prostatitis, it is unclear to what degree the prostate
is the source of symptoms [2].
&
&
&
&
&
Trichomonas spp
Candida spp
Chlamydia trachomatis
Ureaplasma urealyticum
Mycoplasma hominis
Fastidious Bacteria in Chronic Pelvic Pain Syndrome
Epidemiology
The annual prevalence in the general population of CPPS is
0.5% [3], though the overall prevalence of symptoms suggestive of CP/CPPS is 6.3% [4]. CP most commonly affects
men older than 50 years of age [4].
Etiology
The prostate anatomically has multiple ducts that exhibit nondependent drainage, which potentiates the chronicity of an
infection. Prostate enlargement is natural with ageing, leading
to bladder outlet obstruction with higher pressures during voiding, which leads to urinary reflux. Though refluxing urine is
sterile, it can induce chemical irritation, which could initiate
tubular fibrosis and prostatic stone formation, leading to blocking of secretions due to intraductal obstruction.
Chronic nonbacterial prostatitis may in certain cases actually be due to an occult, chronic bacterial infection, and
some men are at higher risk than others [5]. The common
infections are due to uropathogenic Escherichia coli, as
certain strains have specific capability of penetrating into
prostate cells. Further strains such as Propionibacterium
acnes can be detected only via sophisticated genesequencing and polymerase chain reaction assay technology, which makes the diagnosis difficult. In the prostate cells,
they trigger a genetically linked reaction that sustains the
pain by immunologic and/or neurological mechanisms, even
after the bacteria have been eradicated, which might explain
why antibiotics are generally not helpful in CP. Bacteria
may also resist the body’s defenses, detection techniques,
and antibiotic treatment by getting entrenched in a microscopic slime layer called an exopolysaccharide matrix biofilm. By forming these biofilms within the prostate, E. coli
and related bacterial pathogens may cause chronic
treatment-resistant prostatitis [6].
Other causative organisms include the following:
&
&
&
&
&
Klebsiella pneumoniae
Pseudomonas aeruginosa
Proteus spp
Staphylococcus spp
Enterococcus spp
Among the fastidious bacteria (ie, bacteria that cannot be
isolated on standard culture media) that have been implicated in CPPS are C. trachomatis, the genital mycoplasmas (ie,
U. urealyticum, M. 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 [7].
Key Postulates
&
&
&
&
&
An imbalance between proinflammatory cytokines and
endogenous cytokine inhibitors.
Histologic signs of inflammation were found in one
third of patients diagnosed with CPPS who underwent
prostatic biopsy, according to Pontari and Ruggieri’s
report, suggesting an extraprostatic etiology for CPPS.
Genetic predisposition due to differences in DNA
sequences at chromosomal sites that regulate the production and action of cytokines.
In some men, it is postulated that a breakdown in the
mechanism whereby testosterone inhibits prostatic inflammation may lead to CPPS.
An increase in nerve growth factor (NGF), leading to an
increase in the number and the sensitivity of the pelvic
nerves that transmit pain.
Several other causes have been hypothesized for CPPS,
including:
1. Stress-driven hypothalamic-pituitary-adrenal axis dysfunction and adrenocortical hormone (endocrine) abnormalities [8, 9].
2. Neurogenic inflammation leading to neuropathy and spastic hyperactivity due to an occult neural etiology or an
acquired functional voiding disorder [10–12]. It is hypothesized that dysregulation of the local nervous system due to
past trauma, infection, or an anxious disposition and chronic pelvic testing leads to inflammation that is mediated by
substances released by nerve cells (eg, substance P).
3. Myofascial pain syndrome [13, 14]. Myofascial pain
syndrome is an entity in which past inflammation leads
to a secondary reflex triggering of spasm in the musculature of the pelvic floor, leading to varied symptomatology
[15].
Author's personal copy
Curr Bladder Dysfunct Rep (2012) 7:141–149
Immunology and Climate in Chronic Pelvic Pain
Syndrome
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 bodies. 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 [16]. 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 [17].
The ambient temperature plays a role, as cold is frequently
reported as causing symptom aggravation, and heat is often
reported to be ameliorating [18]. It appears that cold is one of
the factors that can trigger a process resulting in CP/CPPS
[11]. Cold also causes aggravation of symptoms and can
initiate a relapse [19, 20].
History and Physical Examination
An NIH collaborative panel proposed the Chronic Prostatitis
Symptom Index (NIH-CPSI), which is calculated using a
series of 9 questions that contain 21 items and is used to
assess patient history in a standardized and quantifiable
format. These questions are provided below [21].
Physical examination in prostatitis shows:
&
&
&
&
Mildly tender, nodular, or normal gland on digital rectal
examination
Suprapubic tenderness during acute episodes
Tight anal sphincter on digital rectal examination
Normal examination between acute episodes
The value of this examination is to exclude other diagnoses, such as prostate cancer, chronic urethritis/meatitis,
and granulomatous prostatitis.
Chronic Pelvic Pain Syndrome Versus Interstitial
Cystitis
Unfortunately, there is no diagnostic test that can definitively establish or exclude the diagnosis of CPPS or interstitial
cystitis. 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 CP (54%) or BPH (23%) [22]. Interstitial
cystitis had been diagnosed in these patients according to
143
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 symptoms were 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. 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.) [22].
If cystoscopy is planned, it is done under anesthesia and
includes taking a bladder biopsy and hydrodistention to
search for indicative signs of interstitial cystitis [23].
Chronic Pelvic Pain Syndrome Versus Chronic
Urethritis
The distinction between chronic urethritis and CP/CPPS can
prove problematic, an issue discussed by Krieger and Riley
[24]. Of the seven symptoms evaluated in the NIH-CPSI,
three are common to both populations: penile pain, urinary
frequency, and dysuria. The remaining four symptoms are
typical of CP/CPPS: perineal pain, pain in testicles, pain in
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 white blood cells were identified in all
patients with NGU and in 50% of those with CP/CPPS.
Chronic Pelvic Pain Syndrome Versus Cancer
Transitional cell cancer, carcinoma in situ of the bladder,
prostate cancer, neoplasms of the rectum and gastrointestinal tract, and rare tumors of other pelvic organs have manifested as irritative prostatic symptoms and CPPS and must
be considered during diagnosis.
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 men with prostatic inflammation [25].
Author's personal copy
144
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.
Curr Bladder Dysfunct Rep (2012) 7:141–149
A 2010 study found that NGF could also be used as a
biomarker of the condition [37•]. Men with CP/CPPS are
more likely than the general population to suffer from
chronic fatigue syndrome [38] and irritable bowel
syndrome.
Diagnosis
Imaging Studies
There are no definitive diagnostic tests for CP/CPPS. The
presence of an inordinate number of white blood cells 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 CP, CPPS, or both,
found 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 [26].
CP/CPPS may be inflammatory (category IIIa) or noninflammatory (category IIIb), based on levels of pus cells in
EPS. In 2006, Chinese researchers found that men with
categories IIIa and IIIb had significantly and similarly raised
levels of the anti-inflammatory cytokine transforming
growth factor-β1 and the proinflammatory cytokine
interferon-γ in their EPS when compared with controls;
therefore, measurement of these cytokines could be used
to diagnose category III prostatitis [27]. Recent studies have
questioned the distinction between categories IIIa and IIIb
since both categories show evidence of inflammation if pus
cells are ignored, and other more subtle signs of inflammation, such as cytokines, are measured [28].
Analysis of urine and EPS for leukocytes is debatable, as
the differentiation between inflammatory and noninflammatory subgroups of CP/CPPS is not useful [29].
The standard four-glass test may not be clinically accurate
due to high prevalence of white blood cells and positive bacterial cultures in the asymptomatic control population [30]. The
Meares-Stamey four-glass test is now rarely used [31].
Anothaisintawee et al. [32] suggested that a simplified
premassage and postmassage test may prove more efficacious. Experimental tests that could be useful in the future
include tests to measure semen and prostate fluid cytokine
levels, with various studies having shown increases in
markers for inflammation such as elevated levels of cytokines [33], myeloperoxidase [34], and chemokines [35, 36].
Because no diagnostic finding for CPPS has proven definitive, all imaging studies (eg, KUB radiography/ultrasound
scan, 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 and do not warrant
universal application.
Prostate-Specific Antigen Study
PSA testing in men with CPPS symptoms may be helpful in
distinguishing between chronic bacterial prostatitis (ie, an
elevated PSA value) and prostatodynia (ie, a PSA value
within the reference range), though this has not been established in a controlled study [39].
Uroflow and Urine Cytology
Uroflow may show intermittency of flow and weakening of
the urinary stream with a diminished peak urinary flow rate,
and urethral pressure profile may show high maximum
urethral closing pressure. Voided urine cytologies are indicated only in men with occupational exposure to known
toxins or who exhibit persistent microhematuria.
Prostate Biopsy
Prostate biopsy is only useful in category IV sympatomatic
inflammatory prostatitis with elevated PSA levels to exclude
prostate cancer.
Videourodynamics
The main role of urodynamic studies is to rule out another
underlying, unsuspected, but well-defined neuropathy amenable to treatment, which should justify the cost and discomfort associated with the procedure. Videourodynamic
evaluation often reveals evidence of a spastic dysfunction
of the bladder neck and prostatic urethra. Beyond helping to
Author's personal copy
Curr Bladder Dysfunct Rep (2012) 7:141–149
detect occult neuropathies, it may lead to a better understanding of the underlying voiding dysfunctions peculiar to
select subsets of patients with this condition.
Anal sphincter electromyography and/or sphincter function profiles, the reflex reactivity during cystometrography,
and findings indicate the presence of hypertonicity and
failure of the pelvic floor musculature to relax, which are
signs of an underlying myofascial pain syndrome.
Anothaisintawee et al. [40•] contend 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 [41].
Cystoscopy
Although the study results may be entirely normal, cystoscopy may reveal 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 to rule out the presence of other causes of the patient’s
symptoms. The study is preferably done under general anesthesia, as it allows cold mucosal cup biopsies to rule out
carcinoma in situ and for hydrodistention of the bladder to
rule out interstitial cystitis.
Management
Counseling
No known cure exists for CPPS, but treatments based on the
cooperation of patient make this condition more bearable,
and in some, it may improve or stabilize on its own. Reassure the patient that CPPS is a real physical condition, not an
imagined one, is not cancer, is not life threatening, is not a
venereal disease, and is not contagious. 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 [42•].
Treatments
Traditionally, patients have been warned to avoid excessive
intake of prostate irritants, such as tobacco, coffee, tea, soda,
caffeine, spicy foods, and alcohol. Alkalinization of the
urine seems to help some patients; however, highly alkaline
urine can result in discomfort and dysuria. Sitz baths in a
145
deep tub rather than a shallow perineal dip may provide
partial relief from acute exacerbations.
Prostatic Massage
In 1969, Winter recommended prostatic massage one to three
times weekly for 3–4 weeks for chronic infection of the
prostate. Although this maneuver has largely fallen out of
favor due to little evidence, some still revert to it, albeit on a
less frequent schedule, to provide supplementary symptomatic
relief for select patients.
Ejaculation
Patients with enlarged, symptomatically congested glands
are often advised that regular sexual intercourse may alleviate their symptoms, again with little objective evidence, and
this is also objectionable to some patients on moral and
religious grounds.
Myofascial Release Therapy and Paradoxical Relaxation:
Psychotherapeutic Treatment Technique
Myofascial release therapy is a combination of internal and
external trigger-point release that has proven more effective
than standard external massage therapy alone. Paradoxical
relaxation is a methodology used to train autonomic selfregulation and pelvic muscle tension release. Anderson et al.
[43] have developed a protocol that employs a team composed of a urologist, psychologist, and physiotherapist to
provide a multifaceted approach in 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 [43].
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, yet it is not
widely accepted by urologists [43, 44].
Physical Medicine Therapist and Physiotherapist
Pseudodyssynergia, documented on electromyographic and
fluoroscopic findings, responded to treatment with biofeedback and behavior modification in 83% of cases [45]. Significant symptomatic relief has been achieved through
modulation-based therapies such as biofeedback, αblockers, and sacral nerve stimulation [46].
A study by Anderson et al. [47] suggested that pain in at
least a subset of patients with CP/CPPS may result from a
Author's personal copy
146
variant of fibromyalgia. 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 to cause penile pain in the study [47].
Pharmacologic Management
No analgesics are specifically appropriate in the treatment of
prostatitis. 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%) [48].
Medication Summary
According to Meares [49–51], “Antibacterial agents are
neither effective nor indicated in the treatment of nonbacterial prostatitis” [49–51]. If U. urealyticum or C. trachomatis
infection is suggested, a trial treatment of antibiotics may be
considered.
Some patients with CPPS are maintained on long-term,
low-dose regimens such as a single tablet of trimethoprimsulfamethoxazole 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 grampositive organisms has often been dismissed as a contaminant.
However, small studies have found evidence to suggest that
anaerobes and gram-positive aerobes, even coagulasenegative staphylococci, may in fact be pathogens, and appropriate antibiotic therapy has proven effective in select cases
[52]. In CPPS, the normal defense mechanisms that render
bacteria harmless are defective, which may explain why prolonged courses of antibiotics sometimes provide symptomatic
relief for men with CPPS despite the absence of bacteria that
are traditionally considered pathogenic.
Berger [53] observed, “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.”
In a controlled, randomized investigation by the Chronic
Prostatitis Collaborative Research Network-2, pregabalin
Curr Bladder Dysfunct Rep (2012) 7:141–149
failed to show an advantage in relieving discomfort, as measured by the NIH-CPSI. 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 [54].
Alpha-Adrenergic Blockers
These drugs by relieving the secondary smooth muscle spasm
within the bladder neck and prostatic urethra, afford the patient greater comfort in voiding, and have become a mainstay
in the symptomatic treatment of CPPS in men [49–51]. One
study suggested an advantage to the use of α-blockers in
combination with antibiotics over antibiotic therapy alone in
the treatment of chronic bacterial prostatitis [54].
Randomized controlled trials in which benefit was found
included the following drugs and doses:
&
&
&
&
Alfuzosin (5 mg twice daily for 6 months) [55]. Alfuzosin,
modified release 10 mg, may be used as an alternative but
has not been evaluated.
Tamsulosin (0.4 mg for 6 weeks) [56, 57].
Terazosin (1 mg for 4 days, 2 mg for 10 days, then 5 mg
for 12 weeks [14 weeks total], or 5 mg for 8 weeks [58,
59], or 1–2 mg three times daily for 6 months [59]).
Doxazosin (4 mg/d for 6 months) [60].
Other Treatments
Limited evidence of effectiveness (from at least one randomized controlled trial) has been reported for the following
investigational treatments (in alphabetical order):
&
&
&
&
&
&
Finasteride (IbA) [61]
Fluoxetine (IbA) [62]
Mepartricin (IbA) [63]
Pelvic electromagnetic therapy (IbA) [64]
Prostat/poltit (pollen extract) (IbA) [65]
Quercetin (IbA) [66].
The following investigational treatments are of unknown
effectiveness and cannot be recommended because reported
studies are case series, uncontrolled trials, or small randomized controlled trials showing no statistical benefit:
&
&
&
Aerobic exercise [67]
Acupuncture [68]
Allopurinol [69]
Author's personal copy
Curr Bladder Dysfunct Rep (2012) 7:141–149
&
&
&
&
&
&
&
&
&
&
&
&
&
&
Botulinum toxin A [70]
Capsaicin [71]
Cernilton (pollen extract) [72]
Cooled transurethral microwave therapy [73]
Corticosteroids [74]
Ibuprofen [75]
Pentosan polysulfate [76]
Percutaneous tibial nerve stimulation [77]
Sacral magnetic stimulation [78]
Sertraline [79]
Terpene mixture (Rowatinex) [80]
Transurethral needle ablation (TUNA) [81]
Urethro-anal stimulation [82]
Zafirlukast [82].
Tricyclic antidepressants are sometimes tried in CP/
CPPS, but there are no published trials to support their
use. They have been shown to be effective in some patients
with other forms of chronic pain.
Surgery: Transurethral Resection of the Prostate
A widely held opinion among urologists is that transurethral
resection of the prostate (TURP) should be reserved for
patients who have experienced extreme, persistent symptoms
over a protracted period, with no relief from nonoperative
interventions. When TURP is undertaken, completing a thorough resection of all tissues down to the capsule is essential.
The concern is that residual tissue causes obstruction of the
ductal drainage from prostatic acini and might exacerbate the
patient’s symptoms [83].
Conclusions
CP/CPPS is a common condition affecting men of all ages.
Because mortality and serious complications are extremely
uncommon, CP/CPPS is primarily a quality-of-life disease;
therefore, the patient’s perspective is of paramount importance. Interstitial cystitis and CP/CPPS are clinical syndromes characterized by pelvic pain with or without
voiding symptoms such as urgency and frequency. There
are many similarities in their epidemiology, adverse effects
on quality of life, etiology/pathophysiology, natural history,
and response to similar treatments. However, overlapping
clinical definitions and similar entrance criteria for largescale cohort studies make comparisons problematic. Recent
studies have shown that CP/CPPS takes a substantial toll on
physical and mental health. As with other non–life-threatening diseases, the goal of treatment is to maximize quality
and not quantity of life. Scientifically validated methods to
measure patients’ health-related quality of life have been
147
applied in other urological diseases, such as BPH and interstitial cystitis; the same process is now under way in the
study of CP/CPPS. Newer efforts to classify pelvic pain
syndromes should help in our recognition that interstitial
cystitis and CP/CPPS likely are not organ-specific syndromes, but rather urogenital manifestations of regional or
systemic abnormalities.
Disclosure No potential conflicts of interest relevant to this article
were reported.
References
Papers of particular interest, published recently, have been
highlighted as:
• Of importance
1. http://www.chronicprostatitis.com/nihdef.html
2. Potts JM. Chronic pelvic pain syndrome: a non-prostatocentric
perspective. World J Urol. 2003;21:54.
3. Taylor BC, Noorbaloochi S, McNaughton-Collins M, et al. Excessive antibiotic use in men with prostatitis. Am J Med. 2008;121
(5):444–9.
4. Daniels NA, Link CL, Barry MJ, McKinlay JB. Association between past urinary tract infections and current symptoms suggestive of chronic prostatitis/chronic pelvic pain syndrome. J Natl
Med Assoc. 2007;99(5):509–16.
5. NIH Summary Statement. NIDDK Workshop on Chronic Prostatitis, Bethesda, Md. December 1995.
6. Wagenlehner FM, Naber KG. Fluoroquinolone antimicrobial
agents in the treatment of prostatitis and recurrent urinary tract
infections in men. Curr Urol Rep. 2004;5(4):309–16.
7. Dennis LK, Lynch CF, Torner JC. Epidemiologic association between prostatitis and prostate cancer. Urology. 2002;60(1):78–83.
8. Anderson RU, Orenberg EK, Chan CA, Morey A, Flores V.
Psychometric profiles and hypothalamic-pituitary-adrenal axis
function in men with chronic prostatitis/chronic pelvic pain syndrome. J Urol. 2008;179(3):956.
9. Dimitrakov J, Joffe HV, Soldin SJ, Bolus R, Buffington CA,
Nickel JC. Adrenocortical hormone abnormalities in men with
chronic prostatitis/chronic pelvic pain syndrome. Urology.
2008;71(2):261–6.
10. Theoharides TC, Cochrane DE. Critical role of mast cells in
inflammatory diseases and the effect of acute stress. J Neuroimmunol. 2004;146(1–2):1–12.
11. Theoharides TC, Kalogeromitros D. The critical role of mast cells
in allergy and inflammation. Ann N Y Acad Sci. 2006;1088:78–99.
doi:10.1196/annals.1366.025.
12. Sant GR, Kempuraj D, Marchand JE, Theoharides TC. The mast
cell in interstitial cystitis: role in pathophysiology and pathogenesis. Urology. 2007;69(4 Suppl):34–40.
13. Anderson RU, Wise D, Sawyer T, Chan C. Integration of myofascial trigger point release and paradoxical relaxation training treatment of chronic pelvic pain in men. J Urol. 2005;174(1):155–60.
14. Anderson RU, Wise D, Sawyer T, Chan CA. Sexual dysfunction in
men with chronic prostatitis/chronic pelvic pain syndrome: improvement after trigger point release and paradoxical relaxation
training. J Urol. 2006;176(4 Pt 1):1534–8. discussion 1538–9.
Author's personal copy
148
15. Weidner W, Diemer T, Huwe P, Rainer H, Ludwig M. The role of
Chlamydia trachomatis in prostatitis. Int J Antimicrob Agents.
2002;19(6):466–70.
16. Wiygul RD. Prostatitis: epidemiology of inflammation. Curr Urol
Rep. 2005;6(4):282–9.
17. McNaughton Collins M, Pontari MA, O’Leary MP, Calhoun EA,
Santanna J, Landis JR, et al. Quality of life is impaired in men with
chronic prostatitis: the Chronic Prostatitis Collaborative Research
Network. J Gen Intern Med. 2001;16(10):656–62.
18. Hedelin H, Jonsson K. Chronic prostatitis/chronic pelvic pain
syndrome: symptoms are aggravated by cold and become less
distressing with age and time. Scand J Urol Nephrol. 2007;41
(6):516–20.
19. Hedelin H, Jonsson K. Chronic abacterial prostatitis and cold
exposure: an explorative study. Scand J Urol Nephrol. 2007;41
(5):430–5.
20. Gao DJ, Guo YS, Yu HY, Wang YJ, Cui WG. Prevalence and
related factors of prostatitis-like symptoms in young men (in
Chinese). Zhonghua Nan Ke Xue. 2007;13(12):1087–90.
21. http://www.windsorurology.co.uk/Downloads/NIH_Form.pdf.
22. Nickel JC, Shoskes D, Wang Y, Alexander RB, Fowler Jr JE, Zeitlin S,
et al. How does the pre-massage and post-massage 2-glass test compare to the Meares-Stamey 4-glass test in men with chronic prostatitis/
chronic pelvic pain syndrome? J Urol. 2006;176(1):119–24.
23. Magri V, Perletti G, Montanari E, Marras E, Chiaffarino F, Parazzini
F. Chronic prostatitis and erectile dysfunction: results from a crosssectional study. Arch Ital Urol Androl. 2008;80(4):172–5.
24. Schaeffer AJ. Epidemiology and evaluation of chronic pelvic pain
syndrome in men. Int J Antimicrob Agents. 2007;31:108.
25. Meares EM, Stamey TA. Bacteriologic localization patterns in
bacterial prostatitis and urethritis. Invest Urol. 1968;5(5):492–518.
26. Magri V, Wagenlehner FM, Montanari E, Marras E, Orlandi V,
Restelli A, et al. Semen analysis in chronic bacterial prostatitis:
diagnostic and therapeutic implications. Asian J Androl. 2009;11
(4):461–77.
27. Ding XG, Li SW, Zheng XM, Hu LQ. IFN-gamma and TGF-beta1,
levels in the EPS of patients with chronic abacterial prostatitis (in
Chinese). Zhonghua Nan Ke Xue. 2006;12(11):982–4.
28. Pontari A. Inflammation and anti-inflammatory therapy in chronic
prostatitis. Urology. 2002;60(6 Suppl):29–33. discussion 33–4.
29. Weidner W, Anderson RU. Evaluation of acute and chronic bacterial prostatitis and diagnostic management of chronic prostatitis/
chronic pelvic pain syndrome with special reference to infection/
inflammation. Int J Antimicrob Agents. 2007;31(2):91.
30. Nickel JC, Alexander RB, Schaeffer AJ, Landis JR, Knauss JS,
Propert KJ. Leukocytes and bacteria in men with chronic prostatitis/chronic pelvic pain syndrome compared to asymptomatic controls. J Urol. 2003;170(3):818–22.
31. McNaughton CM, Fowler FJ, Elliott DB, Albertsen PC, Barry MJ.
Diagnosing and treating chronic prostatitis: do urologists use the
four-glass test? Urology. 2000;55(3):403–7.
32. Anothaisintawee T, Attia J, Nickel JC, et al. Management of
chronic prostatitis/chronic pelvic pain syndrome: a systematic
review and network meta-analysis. JAMA. 2011;305(1):78–86.
33. He L, Wang Y, Long Z, Jiang C. Clinical significance of IL-2, IL10, and TNF-alpha in prostatic secretion of patients with chronic
prostatitis. Urology. 2009;75(3):654–7.
34. Pasqualotto FF, Sharma RK, Potts JM, Nelson DR, Thomas AJ,
Agarwal A. Seminal oxidative stress in patients with chronic
prostatitis. Urology. 2000;55(6):881–5.
35. Penna G, Mondaini N, Amuchastegui S, Degli Innocenti S, Carini
M, Giubilei G, Fibbi B, Colli E, et al. Seminal plasma cytokines
and chemokines in prostate inflammation: interleukin 8 as a predictive biomarker in chronic prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia. Eur Urol. 2007;51
(2):524–33. discussion 533.
Curr Bladder Dysfunct Rep (2012) 7:141–149
36. Khadra A, Fletcher P, Luzzi G, Shattock R, Hay P. Interleukin8 levels in seminal plasma in chronic prostatitis/chronic pelvic pain
syndrome and nonspecific urethritis. BJU Int. 2006;97(5):1043–6.
37. • Watanabe T, Inoue M, Sasaki K, Araki M, Uehara S, Monden K,
Saika T, Nasu Y, et al. Nerve growth factor level in the prostatic
fluid of patients with chronic prostatitis/chronic pelvic pain syndrome is correlated with symptom severity and response to treatment. BJU Int 2010; no–no. This study depicts the availability of
new biomarkers that have high sensitivity and specificity and that
may aid in further management.
38. Aaron LA, et al. Comorbid clinical conditions in chronic fatigue: a
co-twin control study. J Gen Intern Med. 2001;16(1):24–31.
39. Shoskes DA, Thomas KD, Gomez E. Anti-nanobacterial therapy
for men with chronic prostatitis/chronic pelvic pain syndrome
and prostatic stones: preliminary experience. J Urol. 2005;173
(2):474–7.
40. • Anothaisintawee T, Attia J, Nickel JC, et al. Management of
chronic prostatitis/chronic pelvic pain syndrome: a systematic review and network meta-analysis. JAMA. 2011;305(1):78–86. This
study was a meta- analysis with a systemic review done. It provides
comprehensive details about the causes, implications, and management of CP. This study also emphasizes the test that can be
done even at primary centers without improved medical diagnostic
tools. It also emphasizes the importance of these tests and the
results.
41. Kaplan SA, Volpe MA, Te AE. A prospective, 1-year trial
using saw palmetto versus finasteride in the treatment of category III prostatitis/chronic pelvic pain syndrome. J Urol.
2004;171(1):284–8.
42. • Murphy AB, Macejko A, Taylor A, Nadler RB. Chronic prostatitis: management strategies. Drugs. 2009;69(1):71–84. This study
depicts the involvement of multiple medical departmental care. It is
one of the most neglected aspects of management of CPPS.
43. Anderson RU, Wise D, Sawyer T, Chan C. Integration of myofascial trigger point release and paradoxical relaxation training treatment of chronic pelvic pain in men. J Urol. 2005;174(1):155–60.
44. FitzGerald MP, Anderson RU, Potts J, Payne CK, Peters KM,
Clemens JQ. Randomized multicenter feasibility trial of myofascial physical therapy for the treatment of urological chronic pelvic
pain syndromes. J Urol. 2009;182(2):570–80.
45. Kaplan SA, Santarosa RP, D’Alisera PM, Fay BJ, Ikeguchi EF,
Hendricks J, et al. Pseudodyssynergia (contraction of the external
sphincter during voiding) misdiagnosed as chronic nonbacterial
prostatitis and the role of biofeedback as a therapeutic option. J
Urol. 1997;157(6):2234–7.
46. Lee SH, Lee BC. Electroacupuncture relieves pain in men with
chronic prostatitis/chronic pelvic pain syndrome: three-arm randomized trial. Urology. 2009;73(5):1036–41.
47. Anderson RU, Sawyer T, Wise D, Morey A, Nathanson BH.
Painful myofascial trigger points and pain sites in men with chronic prostatitis/chronic pelvic pain syndrome. J Urol. 2009;182
(6):2753–8.
48. Anderson RU, Wise D, Sawyer T, Chan CA. Sexual dysfunction in
men with chronic prostatitis/chronic pelvic pain syndrome: improvement after trigger point release and paradoxical relaxation
training. J Urol. 2006;176(4 Pt 1):1534–8. discussion 1538–9.
49. Meares Jr EM. Prostatitis. Med Clin North Am. 1991;75(2):405–24.
50. Meares Jr EM. Non-specific infections of the genitourinary tract.
In: Tanagho EH, McAninch JW, editors. Smith’s general urology.
14th ed. Norwalk, Conn: Appleton & Lange; 1995. p. 231–4.
51. Meares Jr EM. Prostatitis and related disorders. In: Walsh PC,
Retik AB, Vaughan ED, Wein AJ, editors. Campbell’s urology.
7th ed. Philadelphia: WB Saunders; 1998. p. 285–6.
52. Lowentritt JE, Kawahara K, Human LG, Hellstrom WJ, Domingue
GJ. Bacterial infection in prostatodynia. J Urol. 1995;154
(4):1378–81.
Author's personal copy
Curr Bladder Dysfunct Rep (2012) 7:141–149
53. Berger R. Editorial comment: urological survey—infection and
inflammation in the genitourinary tract. J Urol. 2009;181:135.
54. Barbalias GA, Nikiforidis G, Liatsikos EN. Alpha-blockers for the
treatment of chronic prostatitis in combination with antibiotics. J
Urol. 1998;159(3):883–7.
55. Mehik A, Alas P, Nickel JC, Sarpola A, Helstrom PJ. Alfuzosin
treatment for chronic prostatitis/chronic pelvic pain syndrome: a
prospective randomised, double-blind, placebo-controlled, pilot
study. Urology. 2003;62:425–9.
56. Cheah PY, Liong ML, Yen KH, et al. Terazosin therapy for chronic
prostatitis/chronic pelvic pain syndrome: a randomized, placebocontrolled trial. J Urol. 2003;169:492–59.
57. Nickel JC, Narayan P, McKay J, Doyle C. Treatment of chronic
prostatitis/chronic pelvic pain syndrome with tamsulosin: a randomised double blind trial. J Urol. 2004;171:1594–7.
58. Batstone RD, Lynch J, Doble A. A randomized-placebo controlled
pilot study of tamsulosin, naproxen and combination in category
IIIA/IIIB chronic prostatitis/chronic pelvic pain syndrome (abstract).
J Urol 2005(suppl 4);173:30.
59. Sivkov A, Oshepkov V, Egorov A, Pataki K. Terazosin in patients
with chronic prostatitis(abstract). BJU Int. 2004;94 suppl 2:5.
60. Cho I, Kim J, Lee K, Lee K, Chang Y. The effect of terazosin on
symptom recurrence in men with chronic prostatitis/chronic pelvic
pain syndrome (abstract). Urology. 2006;68(Suppl 15A):55.
61. Kaplan MA, Volpe MA, Te AE. A prospective 1 year trial using
saw palmetto versus finasteride in the treatment of category III
prostatitis/chronic pelvic pain syndrome. J Urol. 2004;171
(1):284–8.
62. Pavlopoulos PM, Xanthopoulou G, Kakouri P, et al. Fluoxetine in
the management of men with chronic prostatitis/chronic pelvic
pain syndrome (abstract). Urology. 2006;68(Suppl 5A):53–4.
63. De Rose AF, Gallo F, Giglio M, Carmignani G. Role of mepartricin in
category III chronic nonbacterial prostatitis/ chronic pelvic pain syndrome: a randomized prospective placebo-controlled trial. Urology.
2004;63(1):13–6.
64. Rowe E, Smith C, Laverick L, et al. A prospective randomized,
placebo-controlled double-blind study of pelvic electromagnetic
therapy for the treatment of chronic pelvic pain syndrome with
1 year of follow-up. J Urol. 2005;173:2044–7.
65. Elist J. Effects of Pollen Extract Preparation Prostat/Poltit on lower
urinary tract symptoms in patients with chronic nonbacterial prostatitis/chronic pelvic pain syndrome: a randomized double-blind,
placebo-controlled study. Urology. 2006;67(1):60–3.
66. Shoskes DA, Zeitlin SI, Shahed A, Rajfer J. Querectin in men with
category III chronic prostatitis: a preliminary prospective, doubleblind, placebo control trial. Urology. 1999;54:960–3.
67. Giubilei G, Mondaini N, Minervini A, et al. Physical activity of
men with chronic prostatitis/ chronic pelvic pain syndrome not
satisfied with conventional treatments- could it represent a valid
option? The physical activity and male pelvic pain trial: a doubleblind randomized study. J Urol. 2007;177:159–65.
149
68. Chen R, Nickel JC. Acupuncture ameliorates symptoms in men
with chronic prostatitis/chronic pelvic pain snydrome. Urology.
2003;61:1156–9.
69. Persson B, Rondquist G, Ekblom M. Ameliorative effect of allopurinol on non-bacterial prostatitis: a parallel double-blind controlled study. J Urol. 1996;155:961–4.
70. Chuang JC, Chancellor MB. The application of botulinum toxin in
the prostate. J Urol. 2006;176(6):2375–82.
71. Turini D, Beneforti P, Spinelli M, Malagutti S, Lazzeri M. Heat/
burning sensation induced by topical application of capsaicin on
perineal cutaneous area: new approach in diagnosis and treatment
of chronic prostatitis/chronic pelvic pain syndrome? Urology.
2006;67(5):910–3.
72. Rugendorf EW, Weidner W, Ebeling, et al. Results of treatment with
pollen extract (cernilton N) in chronic prostatitis and prostatdynia. Br
J Urol. 1993;71:433–8.
73. Kastner C, Hochreiter W, Huidobro, et al. Cooled transurethral
microwave thermotherapy for intractable chronic prostatitisresults of a pilot study after 1 year. Urology. 2004;64(6):1149–54.
74. Bates SM, Hill VA, Anderson JB, et al. A prospective, randomized
double-blind trial to evaluate the role of a short reducing course of
oral corticosteroid therapy in the treatment of chronic prostatitis/
chronic pelvic pain syndrome. BJU Int. 2007;99:355–9.
75. Lee CB, Ha U-S, Lee SJ, et al. Preliminary experience with a
terpene mixture versus ibuprofen for treatment of category III
chronic prostatitis/chronic pelvic pain syndrome. World J Urol.
2006;24(1):55.
76. Nickel JC, Forrest JB, Tomera K, et al. Pentosan polysulfate
Sodium therapy for men with chronic pelvic pain syndrome: a
mulitcenter, randomized, placebo-controlled study. J Urol.
2005;173:1252–5.
77. Van Balken MR, Vandoninck V, Messelink BJ. Percutaneous tibial
nerve stimulation as neuromodulative treatment of chronic pelvic
pain. Eur Urol. 2003;43:158–63.
78. Leippold T, Strebel RT, Huwyler M, et al. Sacral magnetic stimulation in non-inflammatory chronic pelvic pain syndrome. BJU Int.
2005;95:838–41.
79. Lee RA, West RM, Wilson JD. The response to sertraline in men with
chronic pelvic pain syndrome. Sex Transm Inf. 2005;81:147–9.
80. Leskinen MJ, Kilponen A, Lukkarinin O, Tammela TLJ. Transurethral Needle Ablation for the treatment of chronic pelvic pain syndrome (category III prostatitis): a randomized, sham-controlled study.
Urology. 2002;60:300–4.
81. John H, Ruedi C, Kotting S, Schmid DM, Fatzer M, Hauri D. A
new high frequency electrostimulation device to treat chronic
prostatitis. J Urol. 2003;170:1275–7.
82. Smart CJ, Jenkins JD, Lloyd RS. The painful prostate. Br J Urol.
1975;47(7):861–9.
83. Goldmeier D, Madden P, McKenna M, Tamm N. Treatment of
category IIIA prostatitis with zafirlukast: a randomized controlled
feasibliity study. Int J STD and AIDS. 2005;16(3):196–200.