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Author: Sunil K Ahuja, MD, Chief of Minimally Invasive Urology, Department of Urology, Staff Urologist, Santa Teresa Community Hospital

Sunil K Ahuja is a member of the following medical societies: American Urological Association

Editors: Peter Langenstroer, MD, Assistant Professor, Department of Surgery, Division of Urology, Medical College of Wisconsin; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; J Stuart Wolf, Jr, MD, FACS, David A Bloom Professor of Urology, Director, Division of Minimally Invasive Urology, Department of Urology, University of Michigan Medical Center; Edward David Kim, MD, FACS, Professor of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine; Consulting Staff, University of Tennessee Medical Center

Author and Editor Disclosure

Synonyms and related keywords: nonbacterial prostatitis, chronic pelvic pain syndrome, CPPS, prostatodynia, abacterial prostatitis, noninflammatory chronic pelvic pain syndrome, noninflammatory CPPS, inflammatory chronic pelvic pain syndrome, inflammatory CPPS, asymptomatic inflammatory prostatitis, prostate pain, prostatitis symptom complex, chronic prostatitis symptom index, CPSI, irritative urologic symptoms, obstructive urologic symptoms

Background

Nonbacterial prostatitis refers to a condition that affects patients who present with symptoms of prostatitis without a positive result after urine culture or expressed prostate secretion (EPS) culture. Bacterial causes and their presentations can be reviewed in Acute Bacterial Prostatitis and Prostatic Abscess, Chronic Bacterial Prostatitis, and Prostatitis, Bacterial.

Prior to 1995, the diagnosis of prostatitis was based on the classification of Meares and Stamey, which classified prostatitis into 4 categories: acute bacterial prostatitis, chronic bacterial prostatitis, nonbacterial prostatitis, and prostatodynia.

In 1995, the US National Institutes of Health (NIH) convened a workshop on prostatitis and developed a new classification scheme. The first 2 categories remained the same, ie, acute and chronic bacterial prostatitis. Nonbacterial prostatitis and prostatodynia were combined as category III, ie, chronic abacterial prostatitis/chronic pelvic pain syndrome (CPPS). Category III was further subdivided into IIIa, ie, inflammatory CPPS, and IIIb, ie, noninflammatory CPPS. Category IV encompasses asymptomatic inflammatory prostatitis. See Image 2 for a comparison of the old and new categories of prostatitis.

Prostate specimens often reveal evidence of category IV prostatitis after a biopsy. However, patients with category IV prostatitis have no symptoms. Some physicians treat these patients with antibiotics in an effort to lower their prostate-specific antigen (PSA) level.

The rationale for the new diagnostic classification was to promote additional research to find effective forms of treatment for a symptom complex that cannot always be attributed to a bacterial infection.

Pathophysiology

Of all men evaluated for prostatitis, only 5-10% actually have a true bacteriologic condition as evidenced by a positive urine culture. However, approximately 50% of these men actually receive antibiotics for treatment of the prostatitis symptom complex. Evidence suggests that despite negative culture findings, some patients with nonbacterial prostatitis in the traditional sense may have a bacterial infection. Recent studies found bacterial ribosomal ribonucleic acid (rRNA) by reverse transcriptase-polymerase chain reaction (RT-PCR) in the prostatic fluid of patients with prostatitis symptoms. In addition, some fastidious organisms that do not grow in standard culture media may be the cause of the symptom complex. Some of these organisms are Chlamydia trachomatous, Ureaplasma urealyticum, and Neisseria gonorrhoeae. Despite having nonbacterial prostatitis by the classic definition, these patients improve with an appropriate course of antibiotics.

The pathophysiology of chronic abacterial prostatitis has not been fully elucidated, emphasizing the lack of understanding of this disease complex. However, chronic abacterial prostatitis may involve an etiology similar to that of chronic bacterial prostatitis. The peripheral zone of the prostate is composed of a system of ducts, which possess a poor drainage system that prevents the dependent drainage of secretions. As the prostate enlarges with increasing age, patients develop obstructive symptoms and urine refluxes into the prostatic ducts.

Urine reflux may also occur in patients with urethral stricture disease, voiding dysfunction, or benign prostatic hyperplasia. Refluxing urine, even when it is sterile, may lead to chemical irritation and inflammation. Tubule fibrosis is initiated, and prostatic stones form and lead to intraductal obstruction and stagnation of intraductal secretions. This obstruction initiates an inflammatory response, and prostatitis symptoms develop. A fastidious organism may cause an infection by ascending up the urethra or through reflux of infected urine into the prostatic ducts. Additionally, many men with prostatitis are also more prone to having allergies. Thus, these men may also have autoimmune-mediated inflammation caused by a preceding true infection.

Frequency

United States

Prostatitis symptoms are very common in men aged 35-50 years. These symptoms are the most common urologic problem in men younger than 50 years and the third most common urologic problem in older men. Recent studies using the NIH Chronic Prostatitis Symptom Index (NIH-CPSI) (see Image 1) found the prevalence of prostatitis symptoms to be approximately 10% in a population of men aged 20-74 years. The most common form of prostatitis (90%) is category III, ie, chronic abacterial prostatitis and CPPS.

Mortality/Morbidity

  • Approximately half of all men develop symptoms consistent with prostatitis at some time in their lives. This accounts for 25% of men evaluated for a urologic problem and 8% of all visits to urologists. Prostatitis impairs the patient's quality of life to the same degree as coronary artery disease or Crohn disease. Prostatitis has been shown to have the same effect on a patient's mental health as diabetes mellitus and congestive heart failure.
  • Nonbacterial prostatitis may be caused by fastidious organisms that cannot be cultured routinely from a urinary specimen. A negative routine urine culture result is the reason the syndrome is called nonbacterial prostatitis. These fastidious organisms include C trachomatous, U urealyticum, Trichomonas vaginalis, N gonorrhoeae, viruses, fungi, and anaerobic bacteria.
  • Noninfectious causes of prostatitis have not been proven definitively, but allergies and autoimmune diseases, such as Reiter syndrome, are hypothesized causes. Other purported etiologies are pelvic floor tension myalgia, bladder neck or urethral spasm, and a male variant of interstitial cystitis. One important caveat is that carcinoma in situ of the bladder can also present with irritative urinary symptoms and should be excluded as a cause.

Race

  • No racial predilection is found.

Sex

  • Nonbacterial prostatitis only occurs in males.

Age

  • The common age range for presentation of prostatitis symptoms is 36-74 years.



History

Patients with abacterial prostatitis/CPPS (category III in the 1995 NIH prostatitis classification system) have the same symptom complex as those with chronic bacterial prostatitis. The chief symptom reported in patients with abacterial prostatitis/CPPS is pain.

  • Genitourinary symptoms include perineal, penile tip, testicular, rectal, lower abdominal, or back pain.
  • Patients can also have irritative or obstructive urologic symptoms such as frequency, urgency, dysuria, decreased force of the urinary stream, nocturia, and incontinence.
  • Other symptoms are a clear urethral discharge, ejaculatory pain, hematospermia, and sexual dysfunction.

Physical

In most cases, physical examination findings are nonspecific.

  • Many patients have normal findings, others may have an exquisitely sensitive prostate, and still others may have an enlarged boggy prostate.
  • Uroflowmetry findings may show the patient to have a decreased peak urinary flow.

Causes

  • Nonbacterial prostatitis may be caused by fastidious organisms that cannot be cultured routinely from a urinary specimen. A negative result after routine urine culture is the reason the syndrome is referred to as nonbacterial prostatitis. These fastidious organisms include C trachomatis, U urealyticum, T vaginalis, N gonorrhea, viruses, fungi, and anaerobic bacteria.
  • Noninfectious causes of prostatitis have not been definitively proven, but allergies and autoimmune diseases, such as Reiter syndrome, are hypothesized causes.
  • Other purported etiologies are bladder neck or urethral spasm, a male variant of interstitial cystitis, and pelvic floor tension myalgia.
    • See Interstitial Cystitis for more information.
    • Pelvic floor tension myalgia is also known as levator ani syndrome. This syndrome often is diagnosed based solely on symptoms of a vague dull ache in the rectal area that often worsens when sitting or lying down. Symptoms can last for hours or days. The prevalence rate is approximately 6.6% in the general population and is higher in women. It is observed in persons aged 30-60 years, but incidence decreases in those older than 45 years. Pelvic floor tension myalgia may result from overly contracted pelvic floor muscles due to psychological stress, tension, and anxiety.
  • Carcinoma in situ of the bladder, which can present with irritative urinary symptoms, must be considered and excluded.



Bladder Cancer
Chronic Pelvic Pain
Chronic Pelvic Pain Syndrome and Prostatodynia
Mycoplasma Infections
Nonbacterial Prostatitis
Prostatitis, Bacterial
Prostatitis, Tuberculous
Urethral Strictures

Other Problems to be Considered

Pelvic floor tension myalgia
Dysfunctional voiding
Benign prostatic hyperplasia



Lab Studies

  • A patient with abacterial prostatitis can be evaluated in 2 ways, described as follows:  
    • The first approach is to adhere strictly to the fact that these patients do not have an infection by performing an exhaustive search to exclude an infectious source. This often involves repetitive culturing of EPSs or prostate biopsy specimens using nonstandard culture media for Chlamydia, Ureaplasma, gonorrheal organisms, or anaerobes. Sophisticated research methods using RT-PCR techniques can also be employed. This first approach is very time-consuming and likely only of value in the research setting.
    • A second method involves a trial of antibiotics for 2-4 weeks followed by a reevaluation of the patient for symptomatic improvement. If the patient improves, continued therapy with antibiotics for another 2-4 weeks is required for a clinical cure. This second method is often the one most commonly employed and is used first to treat patients with nonbacterial prostatitis. It succeeds approximately 50% of the time when used over a course of 4-6 weeks. If the patient does not improve with antibiotics, then another cause of symptoms must be sought and different treatment regimens must be initiated until symptoms are controlled.
    • Category III prostatitis is divided into IIIa and IIIb based on whether greater or fewer than 10 WBCs are seen on microscopic examination of the EPS, respectively. However, the management approaches for these two categories do not differ, so they can be grouped together.

Imaging Studies

  • Voiding cystourethrography findings can aid in the diagnosis of bladder neck dysfunction by demonstrating intraprostatic and ejaculatory duct urinary reflux.
  • Retrograde urethrography findings may demonstrate a urethral stricture. This test is indicated if the patient demonstrates decreased peak urinary flow on uroflowmetry findings.

Other Tests

  • If no improvement is observed after treatment with antibiotics and the patient has symptoms that are mostly irritative (eg, dysuria with urinary urgency and frequency), then carcinoma in situ of the bladder must be excluded using urine cytology studies and cystoscopy.
  • Other causes can also be sought, and they are evaluated in no particular order. Further workup is based on the clinical suspicion of the urologist. In addition, some patients may complain of symptoms that are not life-limiting, whereas others are completely limited in their activities of daily life. The search for a cause to these symptoms may be based on each individual, and the appropriate health care consultant should be used for the more esoteric diagnoses.
  • Interstitial cystitis requires a more complex workup. See Interstitial Cystitis.
  • Many patients with abacterial prostatitis have emotional strife and some psychological difficulties (ie, socially, sexually, or both). Patients should be questioned with regard to their overall social adjustment. Stress level is important because stress is responsible for increased tension of the pelvic floor and the internal urinary sphincter, resulting in the symptoms of prostatitis.

Procedures

  • Obstructive symptoms from a urethral stricture can be determined based on uroflow and retrograde urethrogram findings.
  • Prostatic enlargement can be investigated using uroflowmetry or a pressure flow study and the International Prostate Symptom Score.
  • Problems such as pelvic floor tension are more difficult to diagnose, but videourodynamic findings may be helpful in diagnosis. Patient symptoms of a dull ache or pressure in the rectal area may also suggest this diagnosis. A consultation with physical medicine and rehabilitation (PM&R) specialist may be beneficial for these patients.
  • Myofascial trigger point release (TPM), a manipulative therapy that uses pressure on joints and soft tissue as trigger points to relieve pelvic floor muscle dysfunction has been shown to improve symptoms in some patients.



Medical Care

  • Nonbacterial prostatitis may be bacterial, originating from infection with a fastidious organism. Therefore, a 2-week trial of an antibiotic such as trimethoprim-sulfamethoxazole (160 mg/800 mg), levofloxacin (250 mg qd), or ciprofloxacin (500 mg) twice daily for 2 weeks may help lead to the diagnosis. If the patient improves, continue therapy with a full 4- to 6-week course of treatment.
  • Bladder neck dysfunction may be treated with alpha-blockers such as terazosin (2-15 mg) or doxazosin (2-8 mg) given in a dose titration. Flomax (0.4-0.8 mg), a more selective alpha-blocker with fewer adverse effects, may also be tried. Alpha-blocker therapy should be continued for a minimum of 6 months or symptoms may recur.
  • Saw palmetto, an herbal supplement for BPH, has been used with some success. It is hypothesized to work similar to 5-alpha-reductase inhibitors.
  • Finasteride, a 5-alpha-reductase inhibitor, has been shown to be effective in reducing symptoms by decreasing the hormonal response of macrophages and leukocytes and their migration to areas of inflammation. This decreases the subsequent release of tissue-damaging myeloperoxidase, platelet-derived growth factor, and transforming growth factor-beta.
  • Cernilton, a pollen extract product, is thought to have anti-inflammatory activity. Cernilton can be taken 3 times daily for 6 months for symptom improvement. Reports of successful treatment are anecdotal.
  • Quercetin, a flavonoid found in green tea, oranges, onions, and red wine, has also been shown to reduce symptoms, hypothesized to be through its antioxidant and anti-inflammatory activities.
  • Painful symptoms may be treated with ibuprofen (600-800 mg tid).
  • Irritative voiding symptoms of urgency and frequency may be treated with anticholinergics such as oxybutynin (5 mg bid/tid) or tolterodine (1-2 mg bid). Dysuria may be treated short term with Pyridium for 1-2 weeks (100-200 mg tid).
  • Patients with significant pelvic floor tension may benefit from diazepam (5 mg tid), methocarbamol (1500 mg tid) or cyclobenzaprine (10 mg tid). Sitz baths may be helpful. Manual self-massage of the perianal area may also provide some relief from pelvic floor tension. Biofeedback has also shown to provide some relief from these symptoms, although reports are anecdotal.
  • In an effort to include all possible therapies, note that some evidence suggests that symptoms may improve with the use of allopurinol.  Allopurinol reduces the level of urates of urine refluxing into the prostate. However, long-term data show that allopurinol is no better than placebo in improving symptoms.
  • Pentosan polysulfate has shown some benefit in placebo-controlled trials in reducing pelvic pain symptoms. This suggests a crossover in symptoms and diagnosis with interstitial cystitis.
  • Consider interstitial cystitis, which can be treated with a combination of anticholinergics and behavioral therapy, if a patient is refractory to other therapies. In addition, hydrodistention, dimethyl sulfoxide (DMSO) cocktail instillation (DMSO at 50 mL, heparin at 5000 U, Solu-Medrol at 40 mg, gentamicin at 80 mg) or initiation of pentosan polysulfate oral therapy may be required. Refer to Interstitial Cystitis for more information.
  • For a treatment algorithm, see Image 3 and Special Concerns.

Surgical Care

  • If no other diagnosis is felt to be the cause of the patient's symptoms, perform videourodynamics, voiding cystourethrogram, and/or a cystoscopic evaluation to help determine if bladder neck dysfunction or urethral stricture is the cause.
  • A stricture should be treated with either an open surgical repair or via direct visual internal urethrotomy.
  • If no other cause for symptoms can be found, some patients have had improvement of prostatitis symptoms after transurethral microwave thermotherapy (TUMT). TUMT has been successful in 70% of patients in one study. Some possible reasons for its success are that it may speed up the body's response to inflammation in the gland and promote fibrosis or it may damage the afferent nerve fibers that transmit pain. In addition, patients with tension floor myalgia have been shown to improve after rectal heat therapy. Therefore, the application of heat therapies to the prostate may transmit sufficient energy to also help treat pelvic floor tension.
  • Other ablative procedures that destroy or remove prostate tissue can accomplish the same results for prostatic sources of pain, but these have not been studied in controlled trials. These include interstitial laser, radiofrequency ablation, and transurethral resection of the prostate.
  • Treat carcinoma of the bladder using standard measures after tissue diagnosis has been made.
  • In addition to the other previously mentioned therapies, patients with suspected tension floor myalgia may benefit from biofeedback therapy to help relax the pelvic floor muscles.
  • Acupuncture has been shown to improve pain, urinary symptoms, and quality of life in patients with conditions that are refractory to treatment with antibiotics, alpha-blockers, and anti-inflammatories.1

Consultations

  • Patients who appear to be under significant job or family stress may benefit from consultation with a mental health provider.
  • A PM&R specialist can help with the diagnosis of pelvic floor tension myalgia and potential therapies.

Diet

  • Some foods thought to be irritants to the urinary tract include alcohol, cranberry juice/cranberries, lemon juice, carbonated drinks (especially colas), spicy foods (eg, hot chilies), coffee, acidic foods, and chocolate.
    • Patients should be made aware of these potential irritants and told to limit them one at a time to see if their symptoms improve.
    • The reported success of this is anecdotal, and it will not work for everyone. After being instructed to take note of their reactions to certain foods, some patients can identify the foods that cause more irritation to their urinary system.

Activity

  • Avoiding specific activities will not improve symptoms. This author tells patients that relatively frequent ejaculation (ie, every 3 d) may help improve their symptoms. The rationale for this is that it allows for the natural drainage of secretions from the prostate. Some physicians have advocated frequent prostatic massage to promote prostatic drainage and improve symptoms. The rationale for this stems from studies that have revealed higher intraprostatic pressures in patients with prostatitis. Frequent ejaculation allows the same drainage without repeated invasive and uncomfortable prostatic massages.
  • Perianal self-massage may also offer some relief in conjunction with frequent ejaculation because this may relieve tension in the pelvic floor. The reported success is also anecdotal, but it is worth mentioning to patients with persistent symptoms.



Medical therapy is important in the treatment of nonbacterial prostatitis to decrease the severity of symptoms and to allow patients to return to normal function.

Drug Category: Antibiotics

These are often used on a trial basis despite a negative culture result to check for symptom improvement and to rule out infection with a fastidious organism.

Drug NameTrimethoprim and sulfamethoxazole (Bactrim, Septra)
DescriptionTrimethoprim blocks dihydrofolate reductase, and sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA). These are 2 sequential steps in bacterial biosynthesis of nucleic acids and proteins. May be taken in single- or double-strength form. In adults, most commonly taken in pill form, although a liquid suspension is available.
Adult Dose80 mg TMP/400 mg SMZ PO bid
Pediatric Dose<2 months: Do not administer
>2 months: Not established
ContraindicationsDocumented hypersensitivity, megaloblastic anemia due to folate deficiency
InteractionsMay increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly persons; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine, PABA, methenamine, or cyclosporin. Rarely, Stevens-Johnson syndrome, a life-threatening fulminant epidermolysis, has been related to ongoing Septra therapy
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsDiscontinue at first appearance of skin rash or sign of adverse reaction; obtain CBC counts frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, give 5-15 mg/d leucovorin); caution in folate deficiency (eg, those with chronic alcoholism, who are elderly, who are receiving anticonvulsant therapy, or with malabsorption syndrome); hemolysis may occur in those with G-6-PD deficiency; patients with AIDS may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation; adverse effects include stomach upset, diarrhea, nausea, vomiting, and headache; photosensitivity may occur with prolonged exposure to sunlight or tanning equipment

Drug NameLevofloxacin (Levaquin)
DescriptionDerivative of pyridine carboxylic acid with broad-spectrum bactericidal effect. Penetrates prostate well and is effective against N gonorrhoeae and C trachomatis.
Adult Dose250-500 mg PO qd
Pediatric Dose<18 years: Not recommended
>18 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsAntacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; 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), NSAIDs, sucralfate, quinapril, or live vaccines
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsIn prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy; adverse effects include stomach upset, loss of appetite, diarrhea, nausea, headache, dizziness, and drowsiness; less commonly observed are sleep problems, vaginal discomfort in women, vision problems, ringing in ears, muscle/tendon pain or tenderness, generalized weakness, mental or mood changes, unsteadiness, seizures, fainting, yellowing of the skin or eyes, and easy bruising or bleeding; photosensitivity may occur with prolonged exposure to sunlight or tanning equipment

Drug NameCiprofloxacin (Cipro)
DescriptionFluoroquinolone with activity against pseudomonads, streptococci, MRSA, Staphylococcus epidermidis, and most gram-negative organisms but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth. Diffuses into prostatic fluid and is indicated for the treatment of chronic prostatitis.
Adult Dose250-500 mg PO bid
Pediatric Dose<18 years: Not recommended
>18 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsAntacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; 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), cyclosporin, live vaccines, probenecid, sucralfate, quinapril, and didanosine; may increase or prolong effects of caffeine
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsIn prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy; adverse effects include stomach upset, loss of appetite, diarrhea, nausea, headache, or dizziness; less commonly observed are tendonitis, visual changes, restlessness, ringing in ears, or mental changes; photosensitivity may occur with prolonged exposure to sunlight or tanning equipment

Drug Category: Antihypertensives

Selective alpha-1 receptor blockers relax smooth muscle in the prostate and bladder neck. Found to improve symptoms of prostatic obstruction. First choice in therapy for benign prostatic hyperplasia and can be very effective in patients with prostatitis symptoms by improving urine flow and decreasing irritative symptoms.

Drug NameDoxazosin (Cardura)
DescriptionInhibits postsynaptic alpha-adrenergic receptors, resulting in vasodilation of veins and arterioles and decrease in total peripheral resistance and blood pressure.
Has antihypertensive effects and is recommended to be given hs to prevent patient injury if syncopal episode occurs. If added to the regimen of antihypertensive medicines a patient is already taking, monitor patient's blood pressure while in titration phase. Usually started as a titration up to the effective dose. Available in a starter pack containing 1-, 2-, 4-, and 8-mg tabs. Usual effective dose is 4 or 8 mg.
Adult Dose1 mg hs for 7-14 d, titrate up to 2 mg for next 7-14 d, then up to 4 mg; reassess symptoms and maintain 4-mg dose or increase to 8 mg
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsEffects decrease with coadministration of NSAIDs; effects increase with coadministration of diuretics and antihypertensive medications
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsCaution in renal impairment; may cause marked hypotension following first dose (rise slowly after lying or sitting to avoid dizziness); common adverse effects include dizziness, drowsiness, lightheadedness, headache, constipation, loss of appetite, dry mouth, fatigue, nasal congestion, blurred vision, dry eyes, or insomnia; rarely, priapism occurs; avoid alcohol or activity that may cause patient to become overheated (may increase dizziness and sedating effects)

Drug NameTerazosin (Hytrin)
DescriptionDecreases arterial tone by allowing peripheral postsynaptic blockade. Has minimal alpha-2 effect. Antihypertensive agent and is recommended to be given hs to prevent patient injury if syncopal episode occurs. If given to a patient already on antihypertensive agents, monitor blood pressure routinely while in titration phase.
Usually is titrated up to the effective dose. Available as a starter pack that has doses of 1, 2, 5, and 10 mg.
Available in capsule form and cannot be broken in half easily; therefore, each specific dose must be prescribed.
Adult Dose1 mg PO for 1-2 wk, then 2 mg for PO 1-2 wk, then advanced to 5 mg; reevaluate; may need to advance to 10 mg
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; hypotension
InteractionsEffects decrease with coadministration of NSAIDs; effects increase with coadministration of diuretics and antihypertensive medications; decongestants can counteract antihypertensive effects
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsPatients should be cautioned to rise slowly after sitting or lying to avoid dizziness or syncope; caution in renal impairment; may cause marked hypotension following first dose and with coadministration with beta-blockers; alcohol intake and overexertion should also be avoided to prevent dizziness and drowsiness; adverse effects include dizziness, drowsiness, headache, constipation, fatigue, nasal congestion, and dry eyes

Drug Category: Nonsteroidal anti-inflammatory agents

Inhibit action of cyclooxygenase, which results in decrease of prostaglandin synthesis.

Drug NameIbuprofen (Motrin, Advil, Ibuprin)
DescriptionDOC for patients with mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis. Also has anti-inflammatory and antipyretic properties. Available in 200-, 400-, 600-, and 800-mg doses.
Adult DoseOTC: 400 mg PO tid
Prostatitis: 600-800 mg PO tid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; peptic ulcer disease, recent GI bleeding or perforation, renal insufficiency, or high risk of bleeding
InteractionsCoadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently with lithium, cyclosporin, or digoxin
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
PrecautionsCaution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy; alcohol may increase risk of GI bleed; adverse effects include stomach upset, dizziness, drowsiness, and blurred vision; rarely, ringing in ears, hearing loss, or photosensitivity may occur

Drug Category: Benzodiazepines

Work on limbic system, thalamus, and hypothalamus, inducing a calming effect and relieving anxiety and skeletal muscle spasm.

Drug NameDiazepam (Valium)
DescriptionDepresses all levels of CNS (eg, limbic, reticular formation), possibly by increasing activity of GABA. Available as 2-, 5-, and 10-mg doses.
Adult Dose2-5 mg PO tid/qid for muscle relaxation; increase to 10 mg prn
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity, narrow-angle glaucoma
InteractionsIncreases toxicity of benzodiazepines in CNS with coadministration of phenothiazines, barbiturates, alcohol, MAOIs, kava, and cimetidine
PregnancyD - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
PrecautionsUse of alcohol or other sedatives in conjunction can lead to excessive drowsiness; caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity); smoking can decrease effectiveness; long-term use can lead to dependance; elderly persons may be more sensitive to effects; adverse effects include drowsiness, dizziness, stomach upset, blurred vision, headache, confusion, depression, impaired coordination, change in heart rate, trembling, weakness, memory loss, fatigue, and nightmares

Drug Category: Interstitial cystitis agents

For symptomatic relief of pain, burning, urgency, and frequency associated with prostatitis.

Drug NamePentosan polysulfate sodium (Elmiron)
DescriptionHeparinlike derivative of macromolecular carbohydrate that resembles glycosaminoglycans. Has anticoagulant and fibrinolytic properties. Mechanism of action is unknown but may act to prevent irritative or noxious stimuli in the bladder by inhibiting mucosal cell wall permeability.
Adult Dose100 mg PO tid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsMay increase risk of spontaneous bleeding in patients concurrently taking NSAIDs, ASA, heparin, or Coumadin
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsAdverse effects include stomach upset, nausea, headache, dizziness, or diarrhea

Drug NameDimethyl sulfoxide (Rimso-50)
DescriptionConverted to dimethyl sulfone and dimethyl sulfide in vivo. Used intravesically to treat symptoms of interstitial cystitis. When administered intravesically, patients often complain of garliclike taste.
Adult Dose50 mL of 50% solution instilled into bladder
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsNone reported
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsPerform liver and renal function tests and CBC counts before initiating therapy and every 6 mo thereafter

Drug Category: Alpha-adrenergic blocking agents

Tamsulosin is an antagonist of the alpha-1a receptor found in smooth muscle of prostate and bladder neck. Effective for relieving symptoms of prostatic enlargement.

Drug NameTamsulosin (Flomax)
DescriptionAntagonist of alpha-1a receptor found in prostate and bladder neck. Because it is more selective than alpha-blockers (terazosin and doxazosin), does not require dose titration (has minimal, if any, effect on blood pressure).
Adult Dose0.4-0.8 mg PO qd
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsExcretion may be impaired when used in conjunction with cimetidine; has inconclusive reaction in patients using warfarin; use caution when administering
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsEvaluate for prostate cancer because this may also cause prostatic obstructive symptoms

Drug Category: Uricosurics

Reduce uric acid levels. Has no analgesic or anti-inflammatory activity.

Drug NameAllopurinol (Zyloprim)
DescriptionInhibits xanthine oxidase, the enzyme that synthesizes uric acid from hypoxanthine. Reduces synthesis of uric acid without disrupting biosynthesis of vital purines.
Adult Dose220-300 mg PO qd/bid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsAlcohol decreases effects; increases incidence of skin rash when used concurrently with ampicillin and amoxicillin; large amounts of vitamin C acidify urine and may cause kidney stone formation; inhibits metabolism of azathioprine and mercaptopurine
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsReduce dose in renal insufficiency; monitor liver function and perform CBC counts before initiating therapy and periodically thereafter; caution in pregnancy or breastfeeding; adverse effects include drowsiness, stomach upset, nausea, diarrhea, vomiting, and headache

Drug Category: Flower pollens

Pollen (male flower microspore) enables plant reproduction. Produced in anthers of the flower. May have effects on inflammatory response.

Drug NameCernitin pollen extract (Cernilton, Cervital)
DescriptionMay have anti-inflammatory activity.
Adult Dose1 tab PO tid for 6 mo for symptom improvement
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsNone reported
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsRare reports of stomach upset and skin rash

Drug Category: Muscle relaxants

Helpful in relieving discomfort associated with tonically contracted muscles.

Drug NameMethocarbamol (Robaxin)
DescriptionReduces nerve impulse transmission from spinal cord to skeletal muscle
Adult Dose1.5 g PO qid for 2-3 d; then decrease to 4-4.5 g/d in 3-6 divided doses
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; renal impairment
InteractionsIncreases toxicity of CNS depressants
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCaution in history of seizures

Drug NameCyclobenzaprine (Flexeril)
DescriptionSkeletal muscle relaxant that acts centrally and reduces motor activity of tonic somatic origins, influencing both alpha and gamma motor neurons. Structurally related to tricyclic antidepressants and thus carries some same liabilities.
Adult Dose20-40 mg/d PO divided bid/qid; not to exceed 60 mg/d
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; MAOIs within 14 d
InteractionsCoadministration with MAOIs and tricyclic antidepressants may increase toxicity; may have additive effect when used concurrently with anticholinergics; effects of alcohol, CNS depressants, and barbiturates may be enhanced
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsCaution in angle-closure glaucoma and urinary hesitancy

Drug Category: Anticholinergic agents

Used for treatment of overactive bladder to prevent associated symptoms of urinary frequency, urgency, and incontinence.

Drug NameTolterodine tartrate (Detrol)
DescriptionCompetitive muscarinic receptor antagonist for overactive bladder. Differs from other anticholinergic types in that it has selectivity for urinary bladder over salivary glands. Exhibits high specificity for muscarinic receptors and has minimal activity or affinity for other neurotransmitter receptors and other potential targets, such as calcium channels.
Adult Dose2 mg PO bid; reduce to 1 mg bid if patient does not tolerate medication well
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma
InteractionsPatients being treated with macrolide antibiotics or antifungal agents should not receive doses of tolterodine higher than 1 mg bid
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsDo not give doses > 1 mg bid to patients with significantly reduced hepatic function; caution in renal impairment



Further Outpatient Care

  • If symptoms resolve, patients do not need routine reevaluation. If symptoms do not resolve, periodic reevaluation should be considered. If older than 50 years, the patient should have an annual examination, including a rectal examination and PSA test.

In/Out Patient Meds

Prognosis

  • Prognosis is good if a definitive cause of symptoms can be identified and an effective treatment regimen started.

Patient Education

  • Patients should be instructed to try to limit stress in their lives, which may exacerbate symptoms.
  • Some urologists, the author included, also recommend frequent ejaculation to prevent a buildup or stasis of secretions within the prostate, thus avoiding inflammation and prostatitis symptoms.
  • In addition, patients should be told that certain foods (see Diet) may cause more irritation; and, with a little experimenting, they can determine which foods to avoid or limit.
  • For excellent patient education resources, visit eMedicine's Men's Health Center and Prostate Health Center. Also, see eMedicine's patient education articles Prostate Infections and Erectile Dysfunction.



Medical/Legal Pitfalls

  • Failing to consider bladder cancer as a cause for irritative voiding symptoms is a serious pitfall because bladder cancer can be cured if diagnosed in the early stages; a delay in diagnosis can result in the development of metastatic disease.

Special Concerns

  • The goal of the new NIH classification system was to try to classify prostatitis into distinct categories to help stimulate research on the causes of this enigmatic disease. Research into the causes of prostatitis in its myriad forms is still at an early stage, and new discoveries of the etiologies of the symptom complex will no doubt lead to more successful treatments.
  • See Image 3 for a treatment algorithm.
    • Nonbacterial prostatitis can be a very time consuming and difficult disease to treat. A typical patient the author sees presents with a constellation of symptoms consistent with prostatitis. In the initial office setting, the patient is given a copy of the NIH-CPSI (see Image 1) to complete. If the patient has normal findings after urinalysis, a rectal examination with prostatic massage and evaluation of the EPS is performed. If evidence of inflammation is present (>10 WBCs per high-power field), a trial of antibiotics is administered, along with alpha-blockers and instructions to ejaculate every 3 days. A postmassage urine culture may be sent for analysis. If the EPS culture results are negative, then the same treatment is applied minus the antibiotics. A PSA blood test is not sent at this time because the massage may skew the results.
    • Patients are usually seen again after 1 month, symptoms are reevaluated, and another NIH-CPSI form is completed. If symptoms have resolved, antibiotics are stopped. Alpha-blockers may be continued at the discretion of the treating physician. Patients with continued symptoms undergo a second prostate massage and EPS evaluation. If inflammation is still present, a full 6-week course of antibiotics is prescribed.
    • Upon reevaluation at 2 months, symptoms are reviewed again. For patients with continued inflammation and symptoms, other causes are sought such as reflux of urine into the prostate, which may be indicative of a urethral stricture or enlargement of the prostate. If either process is suggested, a uroflow examination and/or retrograde urethrogram is performed. If the findings from these are normal, he may have increased pelvic floor tension and a trial of Valium or baclofen may be initiated. If these agents are unsuccessful, referral to a PM&R specialist or treatment with TUMT may be effective.
    • Medications that may be effective at this point are NSAIDs, Cernilton (ie, for their anti-inflammatory qualities), and quercetin. If urinary urgency and frequency are a problem, anticholinergic medicines may be prescribed. Also, do not forget to order a cytology examination to help exclude bladder cancer. If pain with urination is a problem, consider interstitial cystitis.
    • The stress level of the individual should also be evaluated, and referral to a psychologist may be initiated if needed.



For additional information, see Medscape’s Prostatitis Resource Center



Media file 1:  Nonbacterial prostatitis. National Institutes of Health Chronic Prostatitis Symptom Index.
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Media type:  Image

Media file 2:  Nonbacterial prostatitis. Comparison of new and old prostatitis classifications.
Click to see larger pictureClick to see detailView Full Size Image
Media type:  Image

Media file 3:  Treatment algorithm for nonbacterial prostatitis.
Click to see larger pictureClick to see detailView Full Size Image
Media type:  Image



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Nonbacterial Prostatitis excerpt

Article Last Updated: Mar 18, 2008