Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition with a heterogeneous origin that responds best to multimodal therapy. The bioflavonoid quercetin has antioxidant and antiinflammatory effects that have proven useful for treating this condition. Using the clinical phenotype system UPOINT, quercetin can be helpful for those with organ-specific complaints (bladder or prostate) and pelvic floor spasm. This article discusses the current understanding of CP/CPPS and how treatment with quercetin can be used alone or as part of multimodal therapy.
The prostatitis syndromes are some of the most prevalent conditions in urology but also the most poorly understood. Although little controversy exists over the therapy for documented acute or chronic bacterial infections, most patients fall into the nonbacterial or prostatodynia group, now referred to as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) or National Institutes of Health (NIH) category III. The origin, natural history, and appropriate therapy for these patients are unclear. Patient and physician dissatisfaction with these syndromes is high, making it an area ripe for patient interest in nontraditional and alternative therapies.
The polyphenolic bioflavonoid quercetin is a phytotherapeutic compound that has antiinflammatory and antioxidant properties. Its mechanism of action could be of value for several potential pathways in the origin of CP/CPPS. This article discusses the current understanding of CP/CPPS and how treatment with quercetin can be used alone or as part of multimodal therapy.
Classification
One of the earliest attempts at a classification system for chronic prostatitis was made in 1978 by Drach and colleagues and was based on patient symptoms and localizing bacterial cultures published by Meares and Stamey 10 years earlier. The four-glass test localization study collected first-voided urine (VB1), mid-stream urine (VB2), prostatic fluid (expressed prostatic secretion [EPS]), and post–prostate massage urine (VB3), and subjected each to microscopic white blood cell (WBC) count and EPS. Acute bacterial prostatitis was defined as an acute febrile urinary tract infection (UTI). Chronic bacterial prostatitis was defined as recurrent UTI in which bacteria and WBCs were found in the EPS at levels significantly higher than any found in the premassage urine. The diagnosis of nonbacterial prostatitis was defined as WBCs but not bacteria in EPS or VB3. Finally, prostatodynia was used to refer to patients with typical symptoms but without any WBCs or bacteria recovered from prostatic secretions.
Unfortunately, this four-glass localization test was never formally validated as the basis for a classification system, and is seldom used by most physicians. Still no evidence exists that men with no history of recurrent urinary tract infections but uropathogenic bacterial localized to the prostate experience a different response to therapy from similar patients with no uropathogenic localization. Traditional chronic bacterial prostatitis versus nonbacterial prostatitis responds differently to therapy. Recognizing this, a simpler two-glass test was popularized by Nickel and colleagues as an adequate replacement of the more cumbersome four-glass test. In the two-glass test, only pre– and post–prostate massage urine is examined and cultured.
Recognizing the shortcomings of the current classification system, together with the lack of consensus for treatment, the National Institute of Diabetes and Digestive and Kidney Diseases began an initiative to address prostatitis in 1995. The NIH classification system was ultimately published in 1999. Given the lack of understanding of the basic origin of CP/CPPS, the original etiology-driven classification system was replaced by a symptom/syndrome driven classification. Category I and category II are identical to the acute and chronic bacterial prostatitis of the previous system. Category III/CPPS is defined as the presence of genitourinary pain in the absence of uropathogenic bacterial. Category III was further divided into category IIIA and category IIIB. Category IIIA represents inflammatory CPPS in which WBCs can be found in semen, EPS, or urine after prostatic massage, whereas in category IIIB (noninflammatory CPPS), WBCs are not seen. Category IV, or asymptomatic prostatitis, includes patients without symptoms but for whom WBCs can be found in prostate secretions or in prostate tissue during an evaluation for other disorders (infertility, benign prostate hyperplasia, or prostate cancer). The new classification system has been validated for both research and clinical practice.
Category III (CPPS)
CPPS is both the most common form of prostatitis and the most cryptic. The most common symptom is pain, which may be felt in the lower abdomen, pelvis, perineum, or genitals. Urinary complaints are common and may include both voiding and storage symptoms. Additionally, many complain of erectile dysfunction and ejaculatory pain. CP/CPPS is a significant health problem. Prevalence is between 2% and 16%, depending on the population studied, the epidemiologic method, and the definitions of prostatitis. This prevalence reflects a significant burden on the health system, wherein prostatitis is diagnosed in two million physician visits annually. Furthermore, its financial impact is not negligible, with direct medical costs estimated at $6500 per year per person.
The origin and pathophysiology are controversial, and in fact the disorder likely represents different underlying origins which produce a common symptom complex. Some patients with CPPS may have a true bacterial infection. Detection may be missed because cultures are not properly performed, difficult-to-culture organisms are not searched for (eg, ureaplasma, mycoplasma), or the bacteria may not be identifiable using current culture techniques. In the absence of infection, evidence shows an inflammatory or autoimmune component to CPPS. Even in the absence of visible WBCs, EPS and semen of men with CPPS have elevated levels of inflammatory cytokine and oxidative stress. Furthermore, symptomatic response to antibiotics in patients with CPPS may be from direct antiinflammatory rather than antimicrobial effects of these drugs. Finally, much of the pain of CPPS is likely related to pelvic muscle spasm, which may be secondary to infective or inflammatory conditions mentioned earlier, or may be the primary problem in the absence of any prostatic pathology. Pelvic muscle spasm can lead to chronic intermittent hypoxia, which may be improved by antioxidant therapy.
Category III (CPPS)
CPPS is both the most common form of prostatitis and the most cryptic. The most common symptom is pain, which may be felt in the lower abdomen, pelvis, perineum, or genitals. Urinary complaints are common and may include both voiding and storage symptoms. Additionally, many complain of erectile dysfunction and ejaculatory pain. CP/CPPS is a significant health problem. Prevalence is between 2% and 16%, depending on the population studied, the epidemiologic method, and the definitions of prostatitis. This prevalence reflects a significant burden on the health system, wherein prostatitis is diagnosed in two million physician visits annually. Furthermore, its financial impact is not negligible, with direct medical costs estimated at $6500 per year per person.
The origin and pathophysiology are controversial, and in fact the disorder likely represents different underlying origins which produce a common symptom complex. Some patients with CPPS may have a true bacterial infection. Detection may be missed because cultures are not properly performed, difficult-to-culture organisms are not searched for (eg, ureaplasma, mycoplasma), or the bacteria may not be identifiable using current culture techniques. In the absence of infection, evidence shows an inflammatory or autoimmune component to CPPS. Even in the absence of visible WBCs, EPS and semen of men with CPPS have elevated levels of inflammatory cytokine and oxidative stress. Furthermore, symptomatic response to antibiotics in patients with CPPS may be from direct antiinflammatory rather than antimicrobial effects of these drugs. Finally, much of the pain of CPPS is likely related to pelvic muscle spasm, which may be secondary to infective or inflammatory conditions mentioned earlier, or may be the primary problem in the absence of any prostatic pathology. Pelvic muscle spasm can lead to chronic intermittent hypoxia, which may be improved by antioxidant therapy.
Clinical phenotyping of CPPS
The authors believe that the only rational approach to patients with these disparate mechanisms and symptoms is to develop a phenotype that is clinically meaningful and, most importantly, that can drive and improve therapy. In response to this need, the UPOINT phenotyping classification system was recently developed for patients diagnosed with chronic pelvic pain. UPOINT is a six-point clinical classification system that categorizes patients into six clinically identifiable domains: urinary, psychosocial, organ-specific, infection, neurologic/systemic, and tenderness of skeletal muscle. This clinical classification system is not necessarily based on etiology (but may be eventually) and remains flexible (can incorporate new epidemiology, therapeutic, and biomarker research as it becomes available). The key features of each domain are that they may be scored as positive or negative based on simple clinical criteria, they are discriminative in the populations of interest (ie, it would be of no value if almost all patients fell into a very few phenotypes), and each is associated with specific therapies with at least some reasonable evidence for efficacy. Because mulitmodal therapy is superior to unimodal or stepwise therapy in men and women with pelvic pain, the UPOINT phenotype provides a framework for rational multiple treatment selection.
The authors and others have now studied the UPOINT system in men with category III prostatitis (CPPS). These studies retrospectively evaluated patients with these diagnoses and classified their phenotype as a yes/no for each of the six domains in Box 1 .
- 1.
Urinary
Patient complaint of bothersome urgency, frequency, or nocturia
Post-void residual >100 mL
Obstructive voiding symptoms (or maximum flow rate <15 mL/s)
- 2.
Psychosocial
Clinical depression
Evidence of catastrophizing (helplessness, hopelessness)
- 3.
Organ-specific
Representative tenderness on light palpation of prostate
Leukocytosis in prostatic fluid
Hematospermia
- 4.
Infection
Exclude patients with clinical cystitis or bacterial prostatitis (includes past history of documented UTI associated with initiation or flare)
Atypical bacteria in urine or positive prostatic fluid cultures in absence of UTI
- 5.
Neurologic/systemic conditions
Pain beyond abdomen and pelvis
Irritable bowel syndrome
Fibromyalgia
Chronic fatigue syndrome
- 6.
Tenderness of skeletal muscles
Palpable muscle spasm or myofascial painful trigger points in abdomen and pelvic floor
In 90 men with CPPS the authors found that the percentage of patients with positive responses in each domain was urinary, 52%; psychosocial, 34%; organ-specific, 61%; infection, 16%; neurologic/systemic, 37%; and tenderness, 53%. A significant stepwise increase in total symptom severity occurred as the number of positive domains increased. Other investigators have subsequently replicated these initial observations.
Quercetin: an antiinflammatory and antioxidant nutraceutical
The bioflavonoids are a family of polyphenolic molecules found in a variety of plants that have significant antioxidant and antiinflammatory properties. Quercetin is a member of this family found in red wine, green tea, and onions ( Fig. 1 ). It is a potent free oxygen scavenger, antioxidant, and antiinflammatory agent. It reduces inflammation through inhibiting the production of cytokines such as interleukin (IL)-6, IL-8, and tumor necrosis factor by inhibiting the promoter nuclear factor κB (NF-κB). These cytokines are elevated in the semen and prostate fluid of men with CPPS. Furthermore, in an animal model of inflammatory pain, quercetin reduced pain, oxidative stress, and cytokine production. Absorption of dietary quercetin is variable and dependent on gut flora.
Related posts:
The Complex Interplay Between Cholesterol and Prostate Malignancy
Pollen Extract for Chronic Prostatitis—Chronic Pelvic Pain Syndrome
What Do I Tell Patients About Saw Palmetto for Benign Prostatic Hyperplasia?
Statin Clinical Trial (REALITY) for Prostate Cancer: an Over 15-Year Wait is Finally Over Thanks to a Dietary Supplement
Heart Health = Urologic Health and Heart Unhealthy = Urologic Unhealthy: Rapid Review of Lifestyle Changes and Dietary Supplements
Prostate Imaging Modalities that Can Be Used for Complementary and Alternative Medicine Clinical Studies
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
