Pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome

Juan VA Franco; Tarek Turk; Jae Hung Jung; Yu‐Tian Xiao; Stanislav Iakhno; Federico Ignacio Tirapegui; Virginia Garrote; Valeria Vietto

doi:10.1002/14651858.CD012552.pub2

. 2019 Oct 6;2019(10):CD012552. doi: 10.1002/14651858.CD012552.pub2

Pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome

Juan VA Franco ^1,^✉, Tarek Turk ², Jae Hung Jung ³, Yu‐Tian Xiao ⁴, Stanislav Iakhno ⁵, Federico Ignacio Tirapegui ⁶, Virginia Garrote ⁷, Valeria Vietto ⁸

Editor: Cochrane Urology Group

PMCID: PMC6778620 PMID: 31587256

Abstract

Background

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder in which the two main clinical features are pelvic pain and lower urinary tract symptoms. There are currently many approaches for its management, using both pharmacological and non‐pharmacological interventions. The National Institute of Health ‐ Chronic Prostatitis Symptom Index (NIH‐CPSI) score is a validated measure commonly used to measure CP/CPPS symptoms. We considered a 25% decrease of NIH‐CPSI baseline score or a six‐point reduction as MCID.

Objectives

To assess the effects of pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome.

Search methods

We performed a comprehensive search using CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, trial registries, grey literature and conference proceedings, with no restrictions on the language of publication or publication status. The date of the latest search of all databases was July 2019.

Selection criteria

We included randomised controlled trials. Inclusion criteria were men with a diagnosis of CP/CPPS. We included all available pharmacological interventions compared to placebo or in head‐to‐head comparisons.

Data collection and analysis

Two review authors independently assessed study eligibility, extracted data, and assessed the risks of bias of included studies. We assessed the quality of the evidence (QoE) using the GRADE approach.

Main results

We included 99 unique studies in 9119 men with CP/CPPS, with assessments of 16 types of pharmacological interventions. Unless stated otherwise, our comparisons were based on short‐term follow‐up (less than 12 months). Most studies did not specify their funding sources; 21 studies reported funding from pharmaceutical companies.

1. Alpha blockers: (24 studies, 2061 participants). We are uncertain about the effects of these drugs on prostatitis symptoms when compared to placebo at short‐term follow‐up (mean difference (MD) in total NIH‐CPSI score −5.01, 95% confidence interval (CI) −7.41 to −2.61; 18 studies, 1524 participants, very low QoE) and at long‐term follow‐up (MD −5.60, 95% CI −10.89 to −0.32; 4 studies, 235 participants, very low QoE). Alpha blockers may be associated with an increased incidence of adverse events, such as dizziness and postural hypotension (risk ratio (RR) 1.60, 95% CI 1.09 to 2.34; 19 studies, 1588 participants; low QoE). Alpha blockers probably result in little to no difference in sexual dysfunction, quality of life and anxiety and depression (moderate to low QoE).

2. 5‐alpha reductase inhibitors (5‐ARI): (2 studies, 177 participants). Finasteride probably reduces prostatitis symptoms compared to placebo (NIH‐CPSI score MD −4.60, 95% CI −5.43 to −3.77; 1 study, 64 participants; moderate QoE) and may not be associated with an increased incidence of adverse events (low QoE). There was no information on sexual dysfunction, quality of life or anxiety and depression.

3. Antibiotics: (6 studies, 693 participants). Antibiotics (quinolones) may reduce prostatitis symptoms compared to placebo (NIH‐CPSI score MD −2.43, 95% CI −4.72 to −0.15; 5 studies, 372 participants; low QoE) and are probably not associated with an increased incidence in adverse events (moderate QoE). Antibiotics probably result in little to no difference in sexual dysfunction and quality of life (moderate QoE). There was no information on anxiety or depression.

4. Anti‐inflammatories: (7 studies, 585 participants). Anti‐inflammatories may reduce prostatitis symptoms compared to placebo (NIH‐CPSI scores MD −2.50, 95% CI −3.74 to −1.26; 7 studies, 585 participants; low QoE) and may not be associated with an increased incidence in adverse events (low QoE). There was no information on sexual dysfunction, quality of life or anxiety and depression.

5. Phytotherapy: (7 studies, 551 participants). Phytotherapy may reduce prostatitis symptoms compared to placebo (NIH‐CPSI scores MD −5.02, 95% CI −6.81 to −3.23; 5 studies, 320 participants; low QoE) and may not be associated with an increased incidence in adverse events (low QoE). Phytotherapy may not improve sexual dysfunction (low QoE). There was no information on quality of life or anxiety and depression.

6. Botulinum toxin A (BTA): Intraprostatic BTA injection (1 study, 60 participants) may cause a large reduction in prostatitis symptom (NIH‐CPSI scores MD −25.80, 95% CI −30.15 to −21.45), whereas pelvic floor muscle BTA injection (1 study, 29 participants) may not reduce prostatitis symptoms (low QoE). Both comparisons used a placebo injection. These interventions may not be associated with an increased incidence in adverse events (low QoE). There was no information on sexual dysfunction, quality of life or anxiety and depression.

7. Allopurinol: (2 studies, 110 participants). Allopurinol may result in little to no difference in prostatitis symptoms and adverse events when compared to placebo (low QoE). There was no information on sexual dysfunction, quality of life or anxiety and depression.

8. Traditional Chinese medicine (TCM): (7 studies, 835 participants); TCM may reduce prostatitis symptoms (NIH‐CPSI score, MD ‐3.13, 95% CI ‐4.99 to ‐1.28; low QoE) and may not be associated with an increased incidence in adverse events (low QoE). TCM probably does not improve sexual dysfunction (moderate QoE) and may not improve symptoms of anxiety and depression (low QoE). There was no information on quality of life.

The most frequent reasons for downgrading the QoE were study limitations, inconsistency and imprecision. We found few trials with active comparators.

Authors' conclusions

We found low‐ to very low‐quality evidence that alpha blockers, antibiotics, 5‐ARI, anti‐inflammatories, phytotherapy, intraprostatic BTA injection, and traditional Chinese medicine may cause a reduction in prostatitis symptoms without an increased incidence of adverse events in the short term, except for alpha blockers which may be associated with an increase in mild adverse events. We found few trials with active comparators and little evidence of the effects of these drugs on sexual dysfunction, quality of life or anxiety and depression. Future clinical trials should include a full report of their methods, including adequate masking, consistent assessment of all patient‐important outcomes, including potential treatment‐related adverse events, and appropriate sample sizes.

Plain language summary

Intervention for treating chronic prostatitis and chronic pelvic pain in men

Review question

What are the effects of medical therapies in men with longstanding pain and discomfort around their prostate and pelvis, so‐called chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)?

Background

CP/CPPS is a common disorder in which men feel pelvic pain or have bothersome symptoms (or both of these) when urinating. Its cause is unknown and there are many different treatments for this condition.

Study characteristics

The evidence was current to July 2019. We found 96 studies that were conducted between 1983 and 2016 in 8646 men with CP/CPPS, with assessment of 16 types of pharmacological interventions. These therapies were given to men in an outpatient setting. Most studies did not specify their funding sources; 21 studies reported funding from pharmaceutical companies.

Key results

Alpha blockers: we are uncertain about the effects of alpha blockers on prostatitis symptoms. Alpha blockers may increase side‐effects, for example dizziness and low blood pressure. Alpha blockers probably result in little to no difference in sexual problems, quality of life or anxiety and depression.

5‐alpha reductase inhibitors (5‐ARI): 5‐ARI probably reduce prostatitis symptoms and may not be associated with more side effects than seen in men taking a placebo. There was no information on sexual problems, quality of life or anxiety and depression.

Antibiotics: antibiotics may reduce prostatitis symptoms and are probably not associated with side effects. Antibiotics probably result in little to no difference in sexual problems and quality of life. There was no information on anxiety and depression.

Anti‐inflammatories: anti‐inflammatories may reduce prostatitis symptoms and may not be associated with side effects. There was no information on sexual problems, quality of life or anxiety and depression.

Phytotherapy: phytotherapy may reduce prostatitis symptoms and may not be associated with side effects. Phytotherapy may not improve sexual problems. There was no information on quality of life and anxiety and depression.

Botulinum toxin A (BTA): the injection of this toxin into the prostate may cause a large reduction in prostatitis symptoms, but if it is applied to muscles of the pelvis, BTA may not cause this effect. These injections may not be associated with side effects. There was no information on sexual problems, quality of life or anxiety and depression.

Allopurinol: allopurinol may result in little to no difference in prostatitis symptoms and may not be associated with side effects. There was no information on sexual problems, quality of life or anxiety and depression.

Traditional Chinese Medicine (TCM): TCM may reduce prostatitis symptoms and may not be associated with side effects. TCM probably does not improve sexual problems and it may not improve symptoms of anxiety and depression. There was no information on quality of life.

Quality of the evidence

The quality of the evidence was low to very low in most cases, meaning that there is much uncertainty surrounding the results. The most frequent problems detected in the included studies were an inadequate design, a small sample size and a short follow‐up time (usually 12 weeks).

Summary of findings

Background

Description of the condition

Prostatitis is a common disorder affecting 1.8% of men in the USA (Suskind 2013), while 10% to 14% of men in Europe and the USA suffer from prostatitis‐like symptoms (Bajpayee 2012). This health problem motivates one per cent of primary care visits and eight per cent of urology consultations in the USA (Collins 1998). Only 5 to 10 per cent of prostatitis cases have a bacterial origin (Bartoletti 2007; De La Rosette 1993). This disorder can affect men of all ages and ethnic origins, but it is more common in younger men with a mean age at onset of 42 years old (Schaeffer 2002). The two main clinical features of prostatitis are pelvic pain and lower urinary tract symptoms, although there is a wide range of clinical presentations (Nickel 1999).

The National Institutes of Health (NIH) classification identifies four types of prostatitis (Nickel 1999): types I and II, being acute and chronic bacterial prostatitis respectively; type III, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); and type IV, asymptomatic prostatitis. It remains unclear whether type III can be linked in all cases to prostatic involvement (True 1999), hence the alternate denomination (Chronic Pelvic Pain Syndrome). CP/CPPS is sub‐classified as type IIIa (inflammatory), and type IIIb (non‐inflammatory), depending on the presence of inflammatory cells in prostatic secretions.

CP/CPPS is defined when pelvic pain is present for at least three of the preceding six months and no other identifiable causes have been detected (Nickel 1999). Other symptoms include obstructive or irritative voiding difficulties, ejaculatory pain, and haematospermia. Men affected by CP/CPPS have a significantly decreased quality of life, and the level of pelvic pain is strongly associated with sexual dysfunction (Trinchieri 2007; Walz 2007). CP/CPPS is associated with other functional somatic syndromes such as irritable bowel syndrome, interstitial cystitis, chronic fatigue syndrome and fibromyalgia (Rodriguez 2009; Suskind 2013). Diagnosis is usually based on the man's history, physical examination, urinalysis and the two‐ or four‐glass test (Nickel 2012). Further investigations are performed when considering differential diagnosis.

There are different theories about the aetiology and pathophysiology of CP/CPPS, as follows.

Infection: bacterial DNA is detected in a significant proportion of men with CP/CPPS (Hou 2012). A previous history of sexually‐transmitted infection is more frequent in men with CP/CPPS (Pontari 2005). Nevertheless, the isolation of uropathogenic bacteria in prostatic fluids is similar to controls (Nickel 2003a).
Inflammation/autoimmunity: elevated concentrations of pro‐inflammatory cytokines (interleukin 1, tumour necrosis factor, interferon‐γ) and of autoimmunity activity (T‐cell proliferation responses to prostate antigens) is found in men suffering from CP/CPPS and in animal models (Pontari 2004).
Neuropsychological factors: the central nervous system might be involved through several mechanisms of pain sensitisation (Miller 2002; Yang 2003). Increased stress burden, stress response, pain catastrophising cognitions, poor social functioning and psychiatric comorbidity (anxiety and depression) are contributing factors (Riegel 2014).
Dyssynergic voiding associated with bladder neck hypertrophy is detected in men suffering from refractory CP/CPPS (Dellabella 2006; Hruz 2003). Intra‐prostatic urinary reflux and increased intra‐prostatic pressure is associated with inflammation in CP/CPPS (Kirby 1982; Mehik 2002).
Other theories described for this condition include: adrenal axis abnormalities (Anderson 2008), pelvic floor muscles dysfunction (Hetrick 2006; Shoskes 2008a), pelvic nerves entrapment (Antolak 2002), genetic predisposition to inflammation (Shoskes 2002), and oxidative stress (Arisan 2006).

Description of the intervention

There are a wide variety of interventions for treating CP/CPPS, each one addressing a different pathophysiological or symptomatic framework. The diversity of available interventions reflects the complexity of the condition and how little is known about its determinants.

Management of CP/CPPS involves a multimodal and tailored approach (Rees 2015; Shoskes 2008b). Some of the strategies used alone or in combination are the following.

Pharmacological interventions:

Alpha blockers
5‐alpha reductase inhibitors
Antibiotic therapy (quinolones, tetracyclines and other agents)
Anti‐inflammatories (nonsteroidal anti‐inflammatory drugs (NSAIDs), corticosteroids)
Phytotherapy (pollen extract and bioflavonoids)
Botulinum toxin A
Allopurinol
Traditional medicine (traditional Chinese medicine, etc.)
Other pharmacological agents (e.g. pregabalin)

Non‐pharmacological interventions:

Acupuncture and electroacupuncture
Local thermotherapy
Extracorporeal shockwave therapy
Myofascial trigger point release
Biofeedback
Psychological support
Prostatic surgery
Other miscellaneous non‐pharmacological therapies

Multimodal approaches:

Combination therapy: alpha blockers plus antibiotics, antibiotics plus analgesics, etc.

Adverse effects

Common side effects of pharmacological regimens include (Brunton 2011) the following.

Alpha blockers: hypotension, ejaculatory dysfunction, headache, dizziness, and nasal congestion
5‐alpha‐reductase inhibitors: decreased libido, impotence, potentiation of hypotension (in combination with alpha blockers)
Quinolones: gastrointestinal discomfort, headache, dizziness, rash, and tendinopathy
Tetracyclines: gastrointestinal discomfort, rash, teeth discolouration, and hepatotoxicity
NSAIDs: peripheral oedema, rash, dyspepsia, peptic ulcer and bleeding, renal and hepatic injury, and increased risk of adverse cardiovascular events
Phytotherapy: gastrointestinal discomfort and allergic reactions

The most common side effect in physical therapies is pain worsened during or immediately after the procedure (Fitzgerald 2013).

How the intervention might work

Pharmacological interventions

Alpha blockers reduce the autonomic sympathetic tone in the bladder neck and prostate, improving urinary flow, and lower urinary tract symptoms. 5‐alpha‐reductase inhibitors reduce the production of dihydrotestosterone and consequently the size of the prostatic gland dependent on the stimulation of this hormone. This might reduce pain and impaired voiding (Brunton 2011).

NSAIDs are antagonists to the cyclo‐oxygenases enzymes (COX) type 1 and 2 and their pro‐inflammatory sub‐products (Brunton 2011). Both nonselective and selective (COX‐2) inhibitors could therefore decrease inflammatory mediated pain in CP/CPPS.

Phytotherapy includes the use of pollen extract and bioflavonoids that appear to have anti‐inflammatory properties, decreasing acinar cell proliferation and the production of interleukin‐6, tumour necrosis factor α, and other pro‐inflammatory cytokines (Capodice 2005; Kamijo 2001).

Even if CP/CPPS is defined when no bacterial cause can be identified, antibiotics have been used to treat it on the assumption of the existence of an occult or under‐treated infection (Hou 2012).

Allopurinol would reduce the prostatic secretions of purine and pyrimidine base containing metabolites in urine. These metabolites could be responsible for prostatic inflammation through urinary reflux (McNaughton 2002).

Botulinum toxin A has denervating properties and also causes reduction in pain mediators when applied to the prostate in animal models. It also causes apoptosis and involution of the prostate gland (Chuang 2006).

Non‐pharmacological interventions

Acupuncture targets specific cutaneous points representing various internal organs using fine needle insertion and sometimes adding electric current to increase stimulation (electroacupuncture). In animal models electroacupuncture has anti‐inflammatory properties and activates analgesic neurotransmitters (Kim 2006).

Locally‐induced hyperthermia, using transrectal or transurethral procedures, could decrease oxygen free radicals associated with prostatic inflammation (Gao 2012).

Myofascial trigger points release targets pelvic floor musculature dysfunction as a potential cause or contributor to CP/CPPS (Fitzgerald 2013). Biofeedback also addresses pelvic floor muscle through initial contraction in order to achieve further relaxation (Capodice 2005).

It has been suggested that psychological treatments could be helpful in all types of chronic pain syndromes and the psychiatric comorbidity associated with the condition (e.g. depression secondary to chronic pain) (Riegel 2014).

Clinical phenotyping

Clincal phenotyping is a strategy that was developed in order to deliver customised treatment in an aetiologic framework (Shoskes 2008b). The UPOINT system addresses six domains: Urinary symptoms, Psychosocial dysfunction, Organ‐specific findings, Infection, Neurologic dysfunction, and Tenderness of muscles, and offers an algorithmic approach to the use of the aforementioned interventions. The number of affected domains correlates significantly with the prostatitis symptoms score, and the addition of a Sexual dysfunction domain (UPOINT(S)) improves accuracy in stratification of symptom severity (Magri 2010). While in itself it is not an intervention, it serves as a screening tool to select the most appropriate intervention for each person.

Why it is important to do this review

The Cochrane Urology Group undertook an extensive prioritisation exercise to identify a core portfolio of the most clinically important titles. This title was identified as a clinically important priority by the urology expert panel for development, maintenance, and investment of resources by the editorial base.

CP/CPPS is a prevalent condition amongst men and it causes significant impairment of quality of life. There was a previous Cochrane Review on the same subject, but with a different methodological approach (McNaughton Collins 1999). Other non‐Cochrane systematic reviews were also undertaken in previous years: some of them focused on individual interventions (Qin 2016; Yang 2006; Zhu 2014), while others had a wider scope of interventions (Anothaisintawee 2011; Cohen 2012; Magistro 2016). We consider that a new and updated Cochrane Review is needed in order to critically summarise the body of evidence for this complex condition and using the GRADE approach, thus providing key information about the best estimate of the magnitude of the effect in relative terms and absolute differences for patient‐important outcomes. Previous systematic reviews did not use this approach and had variable adherence to the rigorous methodology recommended by Cochrane.

The protocol for this review was first published in August 2016 with the title Interventions for treating chronic prostatitis/chronic pelvic pain syndrome (Franco 2017). Due to the retrieval of a significant number of included studies, the review team and the Cochrane Urology Group decided to split the review into two more narrowly defined reviews: Non‐pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome (Franco 2018) and Pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome.

Objectives

To assess the effects of pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome.

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs). We included studies regardless of their publication status or language of publication.

Types of participants

We included men of all ages, regardless of social condition or ethnic origin, suffering from chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), according with type III prostatitis of the NIH classification.

If we identified studies in which only a subset of participants were relevant to this review, we included them if data were available separately for the relevant subset.

Types of interventions

We planned to investigate the following comparisons of experimental intervention versus comparator intervention. Concomitant interventions have to be the same in the experimental and comparator groups to establish fair comparisons. We performed a condition‐based comprehensive bibliographic search in order to find all interventions tested so far for CP/CPPS; some of them therefore might not be listed in this section.

Pharmacological interventions:

Alpha blockers
5‐alpha reductase inhibitors
Antibiotic therapy (quinolones, tetracyclines and other agents)
Anti‐inflammatories (nonsteroidal anti‐inflammatory drugs (NSAIDs), corticosteroids)
Phytotherapy (pollen extract and bioflavonoids)
Botulinum toxin A
Allopurinol
Traditional medicine (traditional Chinese medicine, etc.)
Other pharmacological agents

Multimodal approaches:

Combination pharmacological therapy: e.g. alpha blockers plus antibiotics, antibiotics plus analgesics, etc.

Comparator interventions

Placebo
No treatment
Other types of pharmacological interventions

Comparisons

We perform head‐to‐head comparisons or intervention versus placebo/no‐treatment comparisons. Pharmacological treatments are compared by drug and by class. For example:

Alpha blockers versus placebo
Alpha blockers plus quinolones versus placebo

And also

Tamsulosin versus placebo
Tamsulosin plus ciprofloxacin versus placebo

We have not included in this review those studies evaluating the comparison between pharmacological and non‐pharmacological interventions, and those which combine non‐pharmacological and pharmacological interventions in the same arm; this is to prevent overlapping with the review Non‐pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome (Franco 2018).

Types of outcome measures

We have not used the measurement of the outcomes assessed in this review as an eligibility criterion.

Primary outcomes

Prostatitis symptoms
Adverse events

Secondary outcomes

Sexual dysfunction
Quality of life (QoL)
Depression and anxiety
Urinary symptoms

Method and timing of outcome measurement

We used the clinically important difference for the review outcomes, to rate the overall quality of the evidence in 'Summary of finding' tables (Johnston 2010). When the mean difference (MD) or risk ratio (RR) was equal to or larger than the minimal clinically important difference (MCID), we assumed that many participants may have gained clinically meaningful improvement from treatment; when the MD was at least half of the MCID but less than the MCID, an appreciable number of participants had probably achieved a clinically meaningful improvement; and when the MD was less than one‐half of the MCID, it was unlikely that an appreciable number of participants achieved clinically meaningful improvement (Johnston 2010).

Prostatitis symptoms

Measured by the National Institutes of Health ‐ Chronic Prostatitis Symptom Index (NIH‐CPSI) as total score and sub‐score measurements, when possible, and other validated scales.
We considered an MCID in NIH‐CPSI score as a 25% decrease or a six‐point reduction from baseline (Nickel 2003b). This threshold was used to measure the 'responders rate' (Cates 2015).

Adverse events

Defined as treatment intolerance, adverse effects of the interventions at any time after participants were randomised to intervention/comparator groups
There was no established threshold for adverse events. We considered the clinically important differences of adverse events above as a relative risk reduction of at least 25% (Guyatt 2011a)

Sexual dysfunction

Measured by validated scales (e.g. International Index of Erectile Function (IIEF))
We considered the MCID in the erectile function domain score of the IIEF to be four (Rosen 2011). We planned to use different thresholds of MCID based on the severity of erectile dysfunction, with a threshold of two for men with mild erectile dysfunction, five with moderate erectile dysfunction and seven with severe erectile dysfunction (Rosen 2011). We also considered an IIEF‐5 of over five points as the MCID (Spaliviero 2010).

Quality of life

Assessed by the Medical Outcomes Study Short Form 12 (SF‐12) or other validated scales
We considered an MCID of SF‐12 physical component score to be eight and SF‐12 mental component score to be four (Parker 2013)

Depression and anxiety

Assessed by Beck Depression Inventory, State Anxiety Inventory‐Y or other validated scales
We considered an MCID of Beck Depression Inventory to be 11 and State Anxiety Inventory‐Y to be 10 (Button 2015; Corsaletti 2014)
We considered an MCID of Hospital Anxiety and Depression scale to be 1.6 (Puhan 2008)

Urinary symptoms

Measured by International Prostate Symptom Score (IPSS) or American Urological Association Symptom Score (AUASS)
We considered improvement of the IPSS score of three points as an MCID to assess efficacy and comparative effectiveness (Barry 1995). We planned to use different thresholds of MCID based on the severity of IPSS, with a threshold of three for men with mild lower urinary tract symptomatology (LUTS), five for moderate LUTS and eight for severe LUTS (Barry 1995).

We considered outcomes measured up to and including 12 months after randomisation as short‐term, and later than 12 months as long‐term.

Main outcomes for 'Summary of findings' tables

We present 'Summary of findings' tables reporting the following outcomes, listed according to priority.

Prostatitis symptoms
Adverse events
Sexual dysfunction
QoL
Depression and anxiety

Search methods for identification of studies

We searched for all published and unpublished RCTs meeting our stated inclusion/exclusion criteria, without restrictions by language, publication date or publication status, and in consultation with the Cochrane Urology Group Information Specialist.

Electronic searches

We identified published, unpublished and ongoing studies by searching the following databases from their inception:

Cochrane Central Register of Controlled Trials (CENTRAL; latest issue in 10 July 2019) in the Cochrane Library;
PubMed (1946 to 10 July 2019);
Embase Elsevier (1947 to 10 July 2019);
PsycINFO OVID (1887 to 10 July 2019);
CINAHL EBSCO (1937 to 10 July 2019);
ClinicalTrials.gov (www.clinicaltrials.gov, 10 July 2019);
ISRCTN Registry (BioMed Central; www.isrctn.com/, 10 July 2019);
World Health Organization International Clinical Trials Registry Platform (www.who.int/trialsearch, 10 July 2019).

We modelled the search strategies for databases on the search strategy designed for PubMed (Appendix 1; Appendix 2; Appendix 3; Appendix 4; Appendix 5; Appendix 6). The PubMed search used the Cochrane Highly Sensitive Search Strategy for identifying randomised trials in MEDLINE: sensitivity maximising version (2008 revision; Lefebvre 2011). The Embase search used the trial filter for therapy, maximising sensitivity developed by the Health Information Research Unit (HIRU) at McMaster University, adapted from OVID to the Elsevier interface (HIRU 2015). For CENTRAL and clinical trials registries filters are not applicable. We did not use filters for PsycINFO and CINAHL because the results likely to be obtained were very few.

Searching other resources

We tried to identify other potentially eligible trials or ancillary publications by searching the reference lists of retrieved included trials and relevant reviews, meta‐analyses and health technology assessment reports. We also contacted authors of included studies to identify any further studies that we may have missed. We contacted drug and device manufacturers for ongoing or unpublished trials. We searched abstract proceedings of the American Urological Association, European Association of Urology and Society of Sexual Medicine of the last three years for unpublished studies (Appendix 7).

We also searched other grey literature sources such as:

Open Grey (www.opengrey.eu/);
New York Academy of Medicine Grey Literature Report (www.greylit.org/);
Google Scholar.

Data collection and analysis

Selection of studies

We used reference management software (EndNote) and Covidence to identify and remove duplicate records. Three review authors (JVAF, TT, VV) working in pairs, independently scanned the abstract, title, or both, of remaining records retrieved, to determine which studies should be assessed further. Five review authors (JVAF, SI, TT, VV, YX) investigated all potentially relevant records in full text, mapped records to studies, and classified studies as included studies, excluded studies, studies awaiting classification or ongoing studies, in accordance with the criteria for each provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a). We used Covidence for title/abstract and full‐text screening. We resolved any discrepancies through consensus or by recourse to a third review author (JHJ). If we could not resolve disagreements, we designated the study as 'awaiting classification' (Characteristics of studies awaiting classification) and we contacted study authors for clarification. We documented reasons for the exclusion of studies that may have reasonably been expected to be included in the review in a Characteristics of excluded studies table. We present an adapted PRISMA flow diagram showing the process of study selection (Liberati 2009).

Data extraction and management

We developed a dedicated data abstraction form that we piloted ahead of time.

For studies that fulfilled our inclusion criteria, seven review authors (FIT, JHJ, JVAF, SI, TT, VV, YX), working in pairs, independently abstracted the following information, which is provided in the Characteristics of included studies table.

Study design;
Study dates (if dates are not available then this will be reported as such);
Study settings and country;
Participant inclusion and exclusion criteria;
Participant details, baseline demographics;
The number of participants by study and by study arm;
Details of relevant experimental and comparator interventions, such as dose, route, frequency, and duration;
Definitions of relevant outcomes, and method and timing of outcome measurement, as well as any relevant subgroups;
Study funding sources;
Declarations of interest by primary investigators.

We further summarise some of the characteristics of the studies, participants and interventions in additional tables (Table 9; Table 10).

1. Description of the interventions by study.

Study	Intervention	Dose	Comparison	Dose for comparison Co‐interventions
Abdalla 2018	Tadalafil study	5 mg daily	Only co‐intervention	Both arms received levofloxacin 500 mg daily
Alexander 2004	Ciprofloxacin + tamsulosin	Ciprofloxacin 500 mg twice daily, tamsulosin 0.4 mg once daily	C1: Ciprofloxacin C2: Tamsulosin C3: Placebo	They used double placebo (factorial design)
Apolikhin 2010	Cernilton® (pollen extract)	2 pills, 3 times a day	Cernilton® (pollen extract)	1 pill, 3 times a day
Bates 2007	Prednisolone	20 mg once daily and then tapered to 5 mg in 1 month	Placebo	Same regimen as active treatment
Breusov 2014	Prolit super (plant extracts)	4 capsules a day	Placebo	Same regimen as active treatment
Cai 2014	Deprox ® (pollen extract)	2 capsules a day	Ibuprofen	600 mg three times daily
Cai 2017	Deprox ® (pollen extract)	2 capsules a day	Bromelain	2 tablets a day
Cavallini 2001	Mepatricin	40 mg daily	Vitamin C (as placebo)	500 mg daily
Cha 2009	Alfusozin	10 mg daily	C1: Terpene mixture 1 capsule three times a day C2: Only co‐intervention	All participants received levofloxacin 300 mg daily
Cheah 2003	Terazosin	Titrated from 1 to 5 mg daily in two weeks	Placebo	Same regimen as active treatment
Chen 2009	Qiantongding decoction	Mix of herbal medications (oral infusion), twice a day	XiaoYanTong (Indometacin)	25 mg tablet three times a day
Chen 2011	Tamsulosin	0.2 mg daily	Placebo	Same regimen as active treatment
Cheng 2010	Levofloxacin	500 mg daily	C1: Ciprofloxacin 500 mg daily C2: Levofloxacin 1 g daily C3: No antibiotic	‐
Choe 2014	Roxithromycin	300 mg daily	C1: Ciprofloxacin 1g daily C2: Aceclofenac 200 mg daily	‐
Churakov 2012	Cytoflavin	10 ml intravenously for 10 days, then 4 pills a day for 20 days	No cytoflavin	Both arms received: α‐blockers ‐ 1 month anti‐inflammatory drugs – 2 weeks prostate massage and vibrovacuum fallostimulation – 10 times antibiotics – 10 days
De Rose 2004	Mepartricin	40 mg daily for 60 days	Placebo	Same regimen as active treatment
Dunzendorfer 1983	Phenoxybenzamine	20 mg daily	Placebo	Same regimen as active treatment
Elist 2006	Pollen extract	74 mg in Prolit® capsules	Placebo	Same regimen as active treatment
Elshawaf 2009	Botulinum toxin A	100 units applied in the external urethral sphincter	Botulinum toxin A	100 units applied to the prostate and sphincter
Erdemir 2010	Quinolone + ibuprofen + terazosin	500 mg, 400 mg and 5 mg respectively	C1: Terazosin 5 mg C2: Quinolone 500 mg + ibuprofen 400 mg	‐
Falahatkar 2015	Botulinum toxin A	200 units applied to the prostate	Placebo	Same regimen as active treatment
Giammusso 2017	Palmitoylethanolamide	300 mg in Penease® capsules twice a day	Serenoa repens	320 mg 1 capsule daily [All] "patients received a full course of pharmacological therapy" before allocation
Giannantoni 2014	Duloxetin	60 mg, escalated during the first 15 days	Only co‐interventions	Co‐interventions included Serenoa repens and tamsulosin
Goldmeier 2005	Zafirlukast	20 mg twice a day	Placebo	Same regimen as active treatment Both arms received doxycycline 100 mg twice daily for 4 weeks
Gottsch 2011	Botulinum toxin A	100 units applied to pelvic floor muscles	Placebo	Same regimen as active treatment
Gül 2001	Terasozin	2 mg daily	Placebo	Same regimen as active treatment
Hu 2015	Bazheng decoction	320 mL daily	Only co‐intervention	Co‐intervention: tamsulosin 0.2 mg a day
Iwamura 2015	Pollen extract	63 mg 3 times a day	Eviprostat® (herbal extract)	1 capsule 3 times a day
Jeong 2008	Levofloxacin	200 mg daily	C1: Doxazosin C2: Levofloxacin + Doxazosin	4 mg daily
Jiang 2009	Desketoprofen	12.5 mg 3 times a day	C1: Indomethacin 25 mg 3 times a day C2: Only co‐interventions	All participants received terazosin 2 mg daily for 4 weeks
Jung 2006	Terazosin	3 ‐ 4 mg	No terazosin	All participants received levofloxacin 300 mg/day, tamiflunate 3 tablets/day for 12 weeks
Kaplan 2004	Serenoa repens	325 mg daily	Finasteride	5 mg daily
Kim 2003	Tamsulosin	0.2 mg daily	C1: Ibuprofen + Misoprostol C2: Tamsulosin + ibuprofen + misoprostol	600 mg ibuprofen three 3 times a day, 300 mcg misoprostol 3 times a day
Kim 2008	Propiverine	20 mg daily	No propiverine	Both groups received gatifloxacin 200 mg twice daily
Kim 2011a	Ciprofloxacin	500 mg twice daily	C1: Diclofenac C2: Only co‐intervention	50 mg twice daily Both groups received tamsulosin 0.2 mg daily for 12 weeks
Kim 2011b	Solifenacin	5 mg daily	No solifenacin	Both groups received ciprofloxacin 1000 mg daily for 8 weeks
Kong 2014	Mirodenafil	50 mg daily	Only co‐intervention	Both groups received levofloxacin 500 mg daily for 6 weeks
Kulovac 2007	Doxazosin	2 mg daily	C1: Ciprofloxacin C2: Doxazosin + ciprofloxacin	500 mg twice a day
Lacquaniti 1999	Terazosin	5 mg daily	C1: Tamsulosin C2: Placebo	0.4 mg daily
Lee 2005	Sertraline	50 mg daily	Placebo	Same regimen as active treatment
Lee 2006a	Terpene mixture	Rowatinex® 200 mg	Ibuprofen	600 mg 3 times a day
Leskinen 1999	Finasteride	5 mg	Placebo	Same regimen as active treatment Ketoprofene was provided to both group for pain relief
Li 2003	QianLieAnShuan (Prostat, 前列安栓)	Herbal suppository each night	Placebo suppository	Same regimen as active treatment
Li 2007	Tiaoshen Tonglin	Mix of herbal medications (oral 150 ml infusion) daily	Terazosin	2 mg daily
Li 2012	Qianlieping	2 g herbal capsule 3 times a day	C1: Tamsulosin C2: Qianlieping + Tamsulosin	0.2 mg daily
Lin 2007	Vardenafil	10 mg daily before sexual intercourse (from week 5 onwards)	Only co‐interventions	Both groups received traditional Chinese medicine (Huafenqinutang oral dose for 8 weeks)
Lu 2004	Phenoxybenzamine	10 mg twice a day	C1: Flavoxate C2: Placebo	200 mg 3 times a day
Macchione 2017	Deprox ® (pollen extract)	2 tablets a day	Serenoa repens	320 mg daily
Maurizi 2019	Deprox ® (pollen extract)	2 tablets a day	Quercetin	500 mg twice daily
Mehik 2003	Alfusozin	5 mg twice a day	Placebo	Same regimen as active treatment Both groups "were allowed to take analgesics (ibuprofen, ketoprofen, diclofenac)"
Mo 2006	Alfusozin	10 mg daily	No alfuzosin	Both groups received levofloxacin 100mg 3 times a day
Morgia 2010	Profluss ® (Serenoa repens + lycopene + seleniated sodium)	320 mg	Serenoa repens	320 mg
Morgia 2017	Curcumin‐calendula	350 mg curcumin and 80 mg calendula in rectal suppositories daily	Placebo	Same regimen as active treatment
Nickel 2003a	Levofloxacin	500 mg daily	Placebo	Same regimen as active treatment
Nickel 2003b	Rofecoxib	50 mg and 25 mg doses daily	C1: Rofecoxib C2: Placebo	All participants had the same regimen All participants were permitted to take up to 2.6 g of paracetamol for rescue analgesia
Nickel 2004a	Finasteride	5 mg daily	Placebo	Same regimen as active treatment
Nickel 2004b	Tamsulosin	0.4 mg daily	Placebo	Same regimen as active treatment
Nickel 2005	Pentosan polysulphate	300 mg 3 times a day	Placebo	Same regimen as active treatment
Nickel 2008	Alfusozin	10 mg daily	Placebo	Same regimen as active treatment
Nickel 2011a	Silodosin	8 mg daily	C1: Silodosin (4 mg) C2: Placebo	Same regimen as active treatment
Nickel 2016	Tanezumab	20 mg intravenous single dose	Placebo	Same regimen as active treatment
Okada 1985	PPC (aminoacid preparation)	6 capsules a day	Pollen extract	Same regimen as active treatment
Park 2005	Cranberry juice	150 ml twice daily	No treatment	All participants underwent an 8 week‐run‐in period with levofloxacin 100mg 3 times a day, NSAID, alpha blocker, behaviour therapy, and hot sitz bath; for non‐responder, 4 additional weeks of same treatments were added
Park 2012	Tadalafil	10 mg daily	Only co‐intervention	Both groups received levofloxacin 500 mg daily for 4 weeks
Park 2017	Tadalafil	5 mg daily	Only co‐intervention	Both groups received levofloxacin 500 mg daily for six weeks
Peng 2003	Antiphlogistic agent	Mixture of herbal remedies 3 times a day	C1: Antiphlogistic + enema C2: Antiphlogistic + suppository C3: Antiphlogistic + "rectal fumigation"	‐
Persson 1996	Allopurinol	300 mg twice a day	C1: Allopurinol 300 mg + placebo C2: Placebo twice a day	Both groups received the same number of pills
Pontari 2010	Pregabalin	Titrated from 150 to 600 mg daily	Placebo	Same regimen as active treatment
Reissigl 2004	Serenoa repens	No description on dose or regimen	Placebo	No description on dose or regimen
Ryu 2007	Alfusozin	10 mg daily	Only co‐intervention	Both groups received tosufloxacin 150mg 3 times a day
Shi 1994	QianLieAnWan	Herbal ball‐shaped formulation, 9g 2 ‐ 3 times a day	C1: QianLieKang C2: Pollen extract capsule	‐
Shoskes 1999	Quercetin	500 mg twice a day	Placebo	Same regimen as active treatment
Singh 2017	Tadalafil	5 mg daily	Only co‐interventions	Both groups received levofloxacin 500 mg for 6 weeks and alfuzosin 10 mg for 6 weeks
Sivkov 2005	Terazosin	Titrated to 5 mg daily	Placebo	Same regimen as active treatment
Sun 2008	QianLieAnTong	Herbal capsule 0.38 g four tables 3 times a day	No QianLieAnTong	Both groups received terazosin 2 mg daily
Tan 2009	QianLieAnShuan (Prostat, 前列安栓)	Herbal suppository each night	No QuanLieAnShuan (Prostant)	Both groups received alpha blockers (tamsulosin or terazosin)
Tugcu 2006	Tiocolchicoside + ibuprofen	120 (sic) and 1200 mg respectively, daily	Only co‐intervention	Both groups received terazosin 5 mg a day
Tuğcu 2007	Tiocolchicoside + ibuprofen + doxazosin	12 mg + 400 mg + 4 mg respectively, daily	C1: Doxazosin C2: Placebo	C1: Doxazosin 4 mg daily
Turkington 2002	Fluvoxamine	50 mg daily	Placebo	Same regimen as active treatment
Wagenlehner 2009	Pollen extract	60 mg carnitine twice a day, daily	Placebo	Same regimen as active treatment Both groups were pretreated with azithromycin (250 mg every 6 hours for 1 day)
Wagenlehner 2014	OM‐89 (E. coli lysate)	6 mg from 18 strains	Placebo	Same regimen as active treatment Other medications were allowed in both groups
Wang 2004	Chuanshentong	Sage and carrot‐family herbal extracts, injected in the prostate	Placebo injection	Same regimen as active treatment
Wang 2016	Terazosin	2 mg daily	C1: Levofloxacin C2: Terazosin + Levofloxacin	Levofloxacin dose: 200 mg twice daily Both groups received dietary advice and prostatic massage once a week and were advised to take warm baths
Wedren 1987	Pentosan polysulphate	100 mg twice daily	Placebo	Same regimen
Wu 2008	Doxazosin	4 mg daily	C1: Diclofenac C2: Doxazosin + diclofenac	75 mg daily
Xia 2014	YuLeShu	Herbal mixture 20 ml 3 times a day	Only co‐interventions	Both groups received levofloxacin 0.2g twice a day, doxazosin 2 mg daily, QianLieTongYu 3 times a day, 4 capsules each time and weekly prostate massage
Xu 2000	Pollen extract (普适泰 = 舍尼通)	0.375 g 3 times a day	Antibiotic treatment	Sulfamethoxazole 2 tablets, twice daily 10 days, ofloxacin 0.2 g, twice daily 10 days, minocycline 0.1 g twice daily, 10 days, sequentially, repeated monthly for 3 months
Yang 2009	Prednisone	15 mg daily	Placebo	Both groups received levofloxacin 100 mg twice a day for 4 weeks
Yang 2010	Terazosin	1 mg daily	C1: Tamsulosin C2: Placebo	0.2 mg daily
Ye 2006	Pollen extract (普适泰 = 舍尼通)	0.375 g twice a day	Placebo	Both groups received levofloxacin 100 mg twice a day for 4 weeks
Ye 2008	Tamsulosin	0.2 mg daily	C1: Levofloxacin C2: Tamsulosin + levofloxacin	Levofloxacin 0.2 g daily
Youn 2008	Doxazosin	Dose was not defined	Only co‐intervention	Both groups received gatifloxacin 200mg twice daily
Zeng 2004	Celecoxib	200 mg daily	Celecoxib	200 mg 3 times a day
Zhang 2007	Aike decoction	Twice daily	C1: Bazhengsan decoction C2: Prostatitis decoction C3: Placebo	All decoctions were administered twice daily
Zhang 2017	Sertraline	Titrated from 50 to 100 mg individually	C1:Duloxetine C2: Only co‐intervention	Duloxeine titrated from 30 to 120 mg individually All participants received doxazosin 4 mg daily
Zhao 2009	Celecoxib	200 mg daily	Placebo	Same regimen
Zhou 2008	Tetracycline	500 mg daily	Placebo	Placebo was "Vitamin B"
Ziaee 2006	Allopurinol	100 mg 3 times a day	Placebo	Same regimen

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C1, C2, C3 were used to refer to multiple treatment arms. NSAID: Nonsteroidal anti‐inflammatory drugs. Blank cells indicate that dosing is described in the adjacent cell and co‐interventions were not described.

2. Description of studies.

Study	n randomised	n analysed	Duration ‐ Follow‐up	Mean age (years) Baseline	Previous treatments	Mean NIH‐CPSI score Baseline	Trial period	Country	Funding
Abdalla 2018	108	108	4 weeks	40.55	N/A	N/A	N/A	Saudi Arabia	None
Alexander 2004	196	174	12 weeks	44.58	N/A	24.78	2001 ‐ 2002	USA and Canada	Government + Industry
Apolikhin 2010	78	78	12 weeks	36.90	N/A	22.50	2008	Russia	None
Bates 2007	21	18	8 weeks 52 weeks	41.05	N/A	24.45	2000 ‐ 2002	UK	Government
Breusov 2014	57	57	8 weeks	N/A	N/A	22.00	N/A	Russia	None
Cai 2014	87	84	4 weeks	33.75	N/A	25.20	2012	Italy	N/A
Cai 2017	70	65	12 weeks	32.60	N/A	25.35	2015	Italy	N/A
Cavallini 2001	54	42	4 weeks	34.00	N/A	N/A	N/A	Italy	N/A
Cha 2009	103	103	8 weeks	39.27	N/A	24.53	2006 ‐ 2008	South Korea	N/A
Cheah 2003	100	86	12 weeks 14 weeks	35.50	N/A	26.15	2000 ‐ 2001	Malaysia and US	Industry
Chen 2009	70	70	4 weeks	29.60	No	24.70	2007 ‐ 2008	China	N/A
Chen 2011	100	93	24 weeks 120 weeks	34.30	No	22.90	2003 ‐ 2007	China	N/A
Cheng 2010	215	215	6 weeks	N/A	Yes	N/A	N/A	Taiwan	N/A
Choe 2014	75	75	4 weeks 12 weeks	29.10	N/A	21.40	2011	South Korea	N/A
Churakov 2012	60	Not ANLZ	4 weeks	N/A	N/A	N/A	N/A	Russia	None
De Rose 2004	30	26	8 weeks	33.00	N/A	25.00	2001 ‐ 2002	Italy	N/A
Dunzendorfer 1983	40	30	6 weeks	39.00	Yes	N/A	N/A	Germany	Industry
Elist 2006	60	58	24 weeks	35.00	Yes	N/A	N/A	USA	Industry
Elshawaf 2009	52	52	52 weeks	36.50	Yes	N/A	N/A	Egypt	N/A
Erdemir 2010	87	87	12 weeks 20 weeks	34.20	N/A	23.92	2004 ‐ 2008	Turkey	N/A
Falahatkar 2015	60	60	24 weeks	40.42	Yes	34.09	2011 ‐ 2013	Iran	N/A
Giammusso 2017	44	44	12 weeks	41.32	N/A	N/A	2014 ‐ 2015	Italy	N/A
Giannantoni 2014	38	34	16 weeks	46.80	N/A	24.68	2009 ‐ 2012	Italy	N/A
Goldmeier 2005	20	17	4 weeks	35.75	N/A	N/A	N/A	UK	Industry
Gottsch 2011	29	29	4 weeks	50.50	Yes	25.95	N/A	USA	N/A
Gül 2001	91	69	12 weeks	39.60	N/A	PSSI 9.61/9.27	1997 ‐ 1999	Turkey	N/A
Hu 2015	96	96	2 weeks	32.15	N/A	27.40	2012 ‐ 2013	China	N/A
Iwamura 2015	100	80	8 weeks	51.55	No	21.30	2009 ‐ 2013	Japan	N/A
Jeong 2008	81	81	6 weeks	40.03	No	23.03	2004	South Korea	N/A
Jiang 2009	115	115	4 weeks	32.48	No	22.43	2007 ‐ 2008	China	N/A
Jung 2006	127	127	12 weeks	N/A	N/A	21.65	2004 ‐ 2005	South Korea	Industry
Kaplan 2004	64	61	52 weeks	43.20	N/A	24.30	N/A	USA	N/A
Kim 2003	63	55	8 weeks 12 weeks	N/A	N/A	18.31	2001 ‐ 2002	South Korea	N/A
Kim 2008	46	46	2 months	40.10	N/A	22.85	N/A	South Korea	University
Kim 2011a	107	100	12 weeks	46.10	N/A	23.56	2008 ‐ 2009	South Korea	N/A
Kim 2011b	96	87	8 weeks	N/A	N/A	21.10	N/A	South Korea	N/A
Kong 2014	88	88	6 weeks	44.75	N/A	20.80	N/A	South Korea	University
Kulovac 2007	90	90	4 weeks	40.30	N/A	25.80	2004	Bosnia and Herzegovina	N/A
Lacquaniti 1999	80	80	8 weeks	36.19	N/A	N/A	1997 ‐ 1998	Italy	N/A
Lee 2005	14	13	13 weeks	N/A	N/A	PSS 23.4/28	N/A	UK	NGO
Lee 2006a	50	50	6 weeks	43.45	N/A	21.87	2003 ‐ 2004	South Korea	N/A
Leskinen 1999	41	35	52 weeks	46.50	Yes	N/A	N/A	Finland	None
Li 2003	76	75	4 weeks	32.70	N/A	48.32	2002	China	N/A
Li 2007	108	108	8 weeks	29.95	N/A	26.05	2004 ‐ 2006	China	Government
Li 2012	257	220	6 weeks	30.60	N/A	24.80	2010 ‐ 2011	China	Government
Lin 2007	138	138	8 weeks	37.00	N/A	27.85	N/A	China	N/A
Lu 2004	60	57	4 weeks	39.13	N/A	21.85	2000 ‐ 2001	China	Government + Industry
Macchione 2017	N/A	63	6 weeks	N/A	N/A	N/A	2016	Italy	None
Maurizi 2019	54	54	4 weeks	33.85	N/A	25.82	2016	Italy	None
Mehik 2003	40	36	24 weeks 52 weeks	49.50	N/A	24.50	N/A	Finland	Government
Mo 2006	54	54	8 weeks	45.25	N/A	23.50	2004 ‐ 2005	South Korea	N/A
Morgia 2010	102	102	8 weeks 16 weeks	38.43	No	27.61	2006 ‐ 2007	Italy	N/A
Morgia 2017	55	48	4 weeks 12 weeks	32.00	No	20.25	2015 ‐ 2016	Italy	None
Nickel 2003a	80	79	6 weeks	56.10	N/A	22.85	N/A	Canada	Government + Industry
Nickel 2003b	161	157	6 weeks	45.97	N/A	21.97	N/A	USA and Canada	Industry
Nickel 2004a	76	64	24 weeks	44.30	N/A	21.30	N/A	USA	Government + Industry
Nickel 2004b	58	58	6 weeks	40.85	N/A	26.30	2000 ‐ 2001	USA	Industry
Nickel 2005	100	73	16 weeks	39.15	N/A	26.45	N/A	USA and Canada	Industry
Nickel 2008	272	233	12 weeks	40.10	N/A	24.45	2005 ‐ 2008	USA, Canada and Malaysia	Government + Industry
Nickel 2011a	151	115	12 weeks	48.30	N/A	26.90	2008 ‐ 2009	Canada	Industry
Nickel 2016	62	51	16 weeks	46.85	N/A	N/A	2009 ‐ 2010	USA, Canada, France, Sweden and Switzerland	Industry
Okada 1985	76	Not ANLZ	4 weeks	N/A	N/A	N/A	1983	Japan	N/A
Park 2005	50	50	12 weeks	35.85	Yes	22.75	2002 ‐ 2003	South Korea	N/A
Park 2012	78	78	4 weeks	N/A	N/A	N/A	N/A	South Korea	None
Park 2017	86	86	6 weeks	48.75	N/A	N/A	N/A	South Korea	N/A
Peng 2003	160	Not ANLZ	4 weeks	36.00	N/A	N/A	1999 ‐ 2002	China	Government
Persson 1996	54	34	32 weeks	N/A	N/A	N/A	N/A	Sweden	N/A
Pontari 2010	324	313	6 weeks	46.60	Yes	26.05	2006 ‐ 2007	USA	Government + Industry
Reissigl 2004	142	142	72 weeks	N/A	N/A	N/A	N/A	Austria	None
Ryu 2007	57	N/A	8 weeks	40.05	N/A	20.70	N/A	South Korea	University
Shi 1994	60	Not ANLZ	4 weeks	N/A	N/A	N/A	1994	China	N/A
Shoskes 1999	30	28	4 weeks	44.85	N/A	20.60	N/A	USA	N/A
Singh 2017	68	61‐65	6 weeks	N/A	N/A	N/A	N/A	India	None
Sivkov 2005	64	51	8 weeks 52 weeks	N/A	N/A	25.70	N/A	Russia	None
Sun 2008	115	115	4 weeks	31.60	No	23.99	2007 ‐ 2008	China	N/A
Tan 2009	90	88	6 weeks	36.01	N/A	24.80	2006	China	N/A
Tugcu 2006	45	39	24 weeks	34.10	N/A	N/A	2003 ‐ 2004	Turkey	N/A
Tuğcu 2007	90	79	24 weeks 52 weeks	29.10	No	22.63	2004 ‐ 2005	Turkey	N/A
Turkington 2002	42	29	8 weeks	41.00	N/A	N/A	N/A	UK	Industry
Wagenlehner 2009	139	118	12 weeks	39.50	N/A	19.80	1999 ‐ 2004	Germany	Industry
Wagenlehner 2014	185	154	24 weeks 52 weeks	47.70	N/A	22.40	2008 ‐ 2010	Austria, Germany, Poland and Portugal	Industry
Wang 2004	38	36	12 weeks	28.00	N/A	N/A	2002 ‐ 2003	China	N/A
Wang 2016	115	115	6 weeks	37.63	No	23.03	2011 ‐ 2014	China	None
Wedren 1987	30	24	12 weeks	37.60	N/A	N/A	1984 ‐ 1985	Sweden	N/A
Wu 2008	123	115	12 weeks	34.80	No	23.96	2006 ‐ 2007	China	N/A
Xia 2014	88	88	4 weeks	34.21	N/A	28.43	2011 ‐ 2012	China	N/A
Xu 2000	60	Not ANLZ	12 weeks	28.25	N/A	N/A	1998 ‐ 1999	China	N/A
Yang 2009	160	158	4 weeks	29.25	N/A	22.61	2007	China	N/A
Yang 2010	156	153	12 weeks	30.73	N/A	25.44	2009	China	N/A
Ye 2006	160	159	8 weeks	31.54	N/A	N/A	2005 ‐ 2006	China	N/A
Ye 2008	105	105	12 weeks	N/A	N/A	20.05	2002 ‐ 2004	China	Industry
Youn 2008	69	N/A	6 weeks	41.55	N/A	24.35	2005 ‐ 2006	South Korea	N/A
Zeng 2004	64	61	6 weeks	35.60	N/A	28.35	2003	China	N/A
Zhang 2007	248	218	4 weeks	30.97	N/A	21.41	2005 ‐ 2007	China	Government
Zhang 2017	150	126	24 weeks	32.96	No	21.94	2011 ‐ 2012	China	None
Zhao 2009	64	64	8 weeks	N/A	No	N/A	2006 ‐ 2008	China	N/A
Zhao 2019	251	114	12 weeks	32.55	N/A	25.22	N/A	China	Government
Zhou 2008	48	48	12 weeks	39.50	Yes	N/A	2005 ‐ 2007	China	N/A
Ziaee 2006	56	56	12 weeks	33.40	N/A	25.68	2002 ‐ 2004	Iran	N/A

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N/A: not applicable; NGO: non‐governmental organization; NIH‐CPSI: National Institutes of Health Chronic Prostatitis Symptom Index; PSS: Prostatitis Severity Score; PSSI: Prostatitis Symptoms Severity Index; USA: United States of America. Duration and follow‐up are differentiated when data were available.

We extracted outcome data relevant to this Cochrane Review as needed for calculation of summary statistics and measures of variance. For dichotomous outcomes, we attempted to obtain numbers of events and totals of population for a 2 × 2 table, as well as summary statistics with corresponding measures of variance. For continuous outcomes, we attempted to obtain means and standard deviations, or data necessary to calculate this information. We resolved any disagreements by discussion, or, if required, by consultation with a third review author (SI or JHJ).

We attempted to contact authors of included studies to obtain key missing data as needed.

We provide information, including trial identifier, about potentially relevant ongoing studies in a Characteristics of ongoing studies table.

Dealing with duplicate and companion publications

In the event of duplicate publications, companion documents or multiple reports of a primary study, we maximised yield of information by mapping all publications to unique studies and collating all available data. We used the most complete data set aggregated across all known publications. In case of doubt, we gave priority to the publication reporting the longest follow‐up associated with our primary or secondary outcomes.

Assessment of risk of bias in included studies

Six review authors (JHJ, JVAF, SI, TT, VV, YX), working in pairs, independently assessed the risks of bias of each included study. We resolved disagreements by consensus, or by consultation with a third review author (JVAF or VV).

We assessed risks of bias using Cochrane's 'Risk of bias' assessment tool (Higgins 2017). We assessed the following domains:

Random sequence generation (selection bias);
Allocation concealment (selection bias);
Blinding of participants and personnel (performance bias);
Blinding of outcome assessment (detection bias);
Incomplete outcome data (attrition bias);
Selective reporting (reporting bias);
Other potential sources of bias.

We judged 'Risk of bias' domains as being at low risk, high risk or unclear risk and evaluated individual bias items as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2017). We present 'Risk of bias' summary figures to illustrate these findings.

For performance bias (blinding of participants and personnel) and detection bias (blinding of outcome assessment), we evaluated the risks of bias separately for each outcome, and we grouped outcomes according to whether they were measured subjectively or objectively when reporting our findings in the 'Risk of bias' tables.

We also assessed attrition bias (incomplete outcome data) on an outcome‐specific basis, and grouped outcomes with similar judgements when reporting our findings in the 'Risk of bias' tables.

We further summarised the risks of bias across domains for each outcome in each included study, as well as across studies and domains for each outcome.

All endpoints are subjective outcomes.

Measures of treatment effect

We expressed dichotomous data as risk ratios (RRs) with 95% confidence intervals (CIs). We expressed continuous data as mean differences (MDs) with 95% CIs unless different studies used different measures to assess the same outcome, in which case we expressed data as standardised mean differences (SMDs) with 95% CIs.

Unit of analysis issues

The unit of analysis was the individual participant. If we identified cross‐over trials, cluster‐randomised trials or trials with more than two intervention groups for inclusion in the review, we handled these in accordance with guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b).

Dealing with missing data

We obtained missing data from study authors, if feasible, and performed intention‐to‐treat analyses if data were available; otherwise, we performed available‐case analyses. We investigated attrition rates, such as dropouts, losses to follow‐up and withdrawals, and we critically appraised issues of missing data. We did not impute missing data. In studies where results were available only graphically we estimated the measurements of the primary outcomes using software in order to describe them in a narrative fashion (Jelicic 2016; PlotDigitalizer).

Assessment of heterogeneity

In the event of excessive heterogeneity unexplained by subgroup analyses, we did not report outcome results as the pooled effect estimate in a meta‐analysis, but have provided a narrative description of the results of each study.

We identified heterogeneity (inconsistency) through visual inspection of the forest plots to assess the amount of overlap of CIs, and the I² statistic, which quantifies inconsistency across studies, to assess the impact of heterogeneity on the meta‐analysis (Higgins 2002; Higgins 2003). We interpreted the I² statistic as follows.

0% to 40%: may not be important.
30% to 60%: may indicate moderate heterogeneity.
50% to 90%: may indicate substantial heterogeneity.
75% to 100%: considerable heterogeneity.

When we found heterogeneity, we attempted to determine possible reasons for it by examining individual study and subgroup characteristics.

Assessment of reporting biases

We attempted to obtain study protocols to assess for selective outcome reporting.

When we included 10 studies or more investigating a particular outcome, we used funnel plots to assess small‐study effects. Several explanations can be offered for the asymmetry of a funnel plot, including true heterogeneity of effect with respect to trial size, poor methodological design (and hence bias of small trials) and publication bias. We therefore interpreted the results cautiously.

Data synthesis

Unless there was good evidence for homogeneous effects across studies, we summarised data using a random‐effects model. We interpreted random‐effects meta‐analyses with due consideration of the whole distribution of effects. We also performed statistical analyses according to the statistical guidelines contained in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a). For dichotomous outcomes, we used the Mantel‐Haenszel method; for continuous outcomes, we used the inverse variance method. We used Review Manager 5 (RevMan 2014) software to perform analyses.

Subgroup analysis and investigation of heterogeneity

We expected the following characteristics to introduce clinical heterogeneity, and planned to carry out subgroup analyses with investigation of interactions.

Participants' characteristics: symptom severity at recruitment, age, presence of clinical comorbidities (irritable bowel syndrome, fibromyalgia, interstitial cystitis).
Duration of the intervention: measured in weeks (e.g. less than 12 weeks or more than 12 weeks).
Presence of combined therapy due to the presence of co‐interventions: e.g. alpha blockers versus placebo, compared to alpha blockers + co‐interventions (antibiotics or analgesics or both) versus co‐interventions alone or in combination with placebo.

We planned to use the test for subgroup differences in Review Manager 5 to compare subgroup analyses if there had been sufficient studies (RevMan 2014).

Sensitivity analysis

We planned to perform sensitivity analyses to explore the influence of the following factors (when applicable) on effect sizes.

Restricting the analysis by taking into account risk of bias, by excluding studies at high risk or unclear risk in at least one domain.
Explore the impact of re‐expressing symptom severity as a dichotomous outcome.
Excluding studies that included participants with a diagnosis of chronic non‐bacterial prostatitis or prostatodynia, not meeting the criteria of the 1999 Research Consensus (Nickel 1999).

'Summary of findings' tables

We presented the overall quality of the evidence for each outcome according to the GRADE approach, which takes into account five criteria related to internal validity (risk of bias, inconsistency, imprecision, publication bias), and external validity, such as directness of results (Guyatt 2008). For each comparison, two review authors (JHJ, JVAF) independently rated the quality of evidence for each outcome as 'high,' 'moderate,' 'low' or 'very low', using GRADEpro GDT. We resolved any discrepancies by consensus, or if needed by arbitration by a third review author (VV). We present a summary of the evidence for the main outcomes in the 'Summary of findings' tables, which provide key information about: the best estimate of the magnitude of the effect in relative terms and absolute differences for each relevant comparison of alternative management strategies; numbers of participants and studies addressing each important outcome; and the rating of the overall confidence in effect estimates for each outcome (Guyatt 2011b; Schünemann 2017). If meta‐analysis was not possible, we present results in a narrative 'Summary of findings' table. We initially planned to present 'Summary of findings' tables for all comparisons, but given their multiplicity, we have presented only those most related to clinical practice in order to highlight the evidence most relevant to clinicians, patients and other stakeholders (see Differences between protocol and review). Nevertheless, we assessed all comparisons using the GRADE approach and they are available under the section Effects of interventions.

We used the controlled vocabulary suggested by Glenton 2010 to summarise the findings of the 'Summary of findings' tables in the 'Plain language summary.'

Results

Description of studies

Results of the search

For detailed information about the results of the search see Figure 1. This review shares the search strategy for the review of non‐pharmacological Interventions for treating chronic prostatitis/chronic pelvic pain syndrome (Franco 2018). In this section we describe the study flow for the studies relevant to the review question. For this review we screened 1725 records. We included four studies from other systematic reviews on this topic (McNaughton 2000; Yang 2008). We discounted 1536 records and obtained the full text for 189 records. We excluded 54 studies (57 records) after full‐text assessment; their characteristics are given in Characteristics of excluded studies tables. We found five studies that could have been completed according to the clinical trial registries but there was no publication available and a two‐stage study with an incomplete report of the conduct of the clinical trial stage (Characteristics of studies awaiting classification). We identified four ongoing studies (see Characteristics of ongoing studies). We included 99 studies (122 records) in this review.

Included studies

We included 99 studies with 9119 participants (see Characteristics of included studies; Table 9; Table 10).

Design

All the included studies were RCTs.

Sample sizes

Median sample size was 76 (interquartile range 55.5 to 107.5). The smallest sample size was 14 and the largest sample size was 324. Sample size was not specified in one study (Macchione 2017).

Setting

Since CP/CPPS is usually treated in an outpatient setting, most studies offered ambulatory care.

Twenty‐eight studies were conducted in China (Chen 2009; Chen 2011; Hu 2015; Jiang 2009; Li 2003; Li 2007; Li 2012; Lin 2007; Lu 2004; Peng 2003; Shi 1994; Sun 2008; Tan 2009; Wang 2004; Wang 2016; Wu 2008; Xia 2014; Xu 2000; Yang 2009; Yang 2010; Ye 2006; Ye 2008; Zeng 2004; Zhang 2007; Zhang 2017; Zhao 2009; Zhao 2019; Zhou 2008), 16 studies were conducted in South Korea (Cha 2009; Choe 2014; Jeong 2008; Jung 2006; Kim 2003; Kim 2008; Kim 2011a; Kim 2011b; Kong 2014; Lee 2006a; Mo 2006; Park 2005; Park 2012; Park 2017; Ryu 2007; Youn 2008), 11 studies were conducted in Italy (Cai 2014; Cai 2017; Cavallini 2001; De Rose 2004; Giammusso 2017; Giannantoni 2014; Lacquaniti 1999; Macchione 2017; Maurizi 2019 Morgia 2010; Morgia 2017), seven studies were conducted in the USA (Elist 2006; Gottsch 2011; Kaplan 2004; Nickel 2004a; Nickel 2004b; Pontari 2010; Shoskes 1999) and seven studies were conducted in more than one country (Alexander 2004; Cheah 2003; Nickel 2003b; Nickel 2005; Nickel 2008; Nickel 2016; Wagenlehner 2014). The remaining studies were conducted in Austria (Reissigl 2004), Bosnia‐Herzegovina (Kulovac 2007), Canada (Nickel 2003a; Nickel 2011a), Egypt (Elshawaf 2009), Finland (Leskinen 1999; Mehik 2003), Germany (Dunzendorfer 1983; Wagenlehner 2009), India (Singh 2017), Iran (Falahatkar 2015; Ziaee 2006), Japan (Iwamura 2015; Okada 1985), Russia (Apolikhin 2010; Breusov 2014; Churakov 2012; Sivkov 2005), Sweden (Persson 1996; Wedren 1987), Taiwan (Cheng 2010), Turkey (Erdemir 2010; Gül 2001; Tugcu 2006; Tuğcu 2007), Saudi Arabia (Abdalla 2018) and the UK (Bates 2007; Goldmeier 2005; Lee 2005; Turkington 2002).

There was a wide variety of languages in the included studies. Twenty‐one studies were written in Chinese (Chen 2009; Hu 2015; Jiang 2009; Li 2003; Li 2007; Li 2012; Lin 2007; Lu 2004; Peng 2003; Shi 1994; Sun 2008; Tan 2009; Wang 2004; Wu 2008; Xia 2014; Xu 2000; Yang 2009; Yang 2010; Ye 2006; Zeng 2004; Zhang 2007), four studies were in Russian (Breusov 2014; Churakov 2012; Apolikhin 2010; Sivkov 2005); eight studies in Korean (Cha 2009; Youn 2008; Kim 2008; Ryu 2007; Mo 2006; Jung 2006; Kim 2003; Park 2005); two in Italian (Cavallini 2001; Lacquaniti 1999), two in Turkish (Erdemir 2010; Tugcu 2006) one in Japanese (Okada 1985) and one in German (Dunzendorfer 1983). This posed some limitations on our review (see Potential biases in the review process). The remaining RCTs were written in English.

Participants

The median age of participants was 38 years (interquartile range 33 to 41). Seventeen studies did not provide information on age (Breusov 2014; Cheng 2010; Churakov 2012; Jung 2006; Kim 2003; Kim 2011b; Lee 2005; Macchione 2017; Okada 1985; Park 2012; Persson 1996; Reissigl 2004; Shi 1994; Singh 2017; Sivkov 2005; Ye 2008; Zhao 2009). Most studies did not include participants over 50 years old, to avoid symptom overlap with benign prostate hyperplasia. Three studies (Gottsch 2011; Iwamura 2015; Nickel 2003a) included older participants (mean age 50 or older). Median symptoms severity, measured by NIH‐CPSI scores, was 24, with a narrow interquartile range of 22 to 26. Only two studies included participants with a NIH‐CPSI score greater than 30 (Li 2003; Falahatkar 2015).

All studies referred to diagnostic criteria aimed at the differentiation of CP/CPPS from other forms of prostatitis and other urological diseases. Participants underwent digital rectal examination, urine cultures and two‐ or four‐glass Meares‐Stamey test. They excluded participants who had recently undergone prostatic biopsy or surgery, participants with prostate cancer, participants with a recent history of sexually‐transmitted diseases and participants with concomitant neurological disorders or severe systemic disorders.

Thirteen studies included participants who had not received other previous treatment (Chen 2009; Chen 2011; Iwamura 2015; Jeong 2008; Jiang 2009; Morgia 2010; Morgia 2017; Sun 2008; Tuğcu 2007; Wang 2016; Wu 2008; Zhang 2017; Zhao 2009). Ten studies specified that participants had previously received medical treatment with antibiotics or alpha blockers (or both) and had not had a positive response (Cheng 2010; Dunzendorfer 1983; Elist 2006; Elshawaf 2009; Falahatkar 2015; Gottsch 2011; Leskinen 1999; Park 2005; Pontari 2010; Zhou 2008). The other studies did not specify whether the participants had received previous treatments for this condition. Nevertheless, a common inclusion criterion was a wash‐out period, as stated in a protocol for medical therapy often cited as a consensus for inclusion/exclusion criteria (Alexander 2004).

Interventions

We included studies assessing a wide variety of pharmacological interventions.

Alpha blockers (Alexander 2004; Cha 2009; Cheah 2003; Chen 2011; Dunzendorfer 1983; Erdemir 2010; Gül 2001; Jeong 2008; Jung 2006; Kim 2003; Kulovac 2007; Lacquaniti 1999; Lu 2004; Mehik 2003; Mo 2006; Nickel 2004b; Nickel 2008; Nickel 2011a; Ryu 2007; Sivkov 2005; Wang 2016; Wu 2008; Yang 2010; Youn 2008).
5‐alpha reductase inhibitors (Leskinen 1999; Nickel 2004a).
Antibiotic therapy (Cheng 2010; Choe 2014; Kim 2011a; Nickel 2003a; Ye 2008; Zhou 2008).
Anti‐inflammatories: Bates 2007; Goldmeier 2005; Jiang 2009; Kim 2003; Kim 2011a; Tuğcu 2007; Wu 2008; Yang 2009; Zhao 2009.
Phytotherapy: (Apolikhin 2010; Breusov 2014; Cai 2014; Cai 2017; Cha 2009; Elist 2006 Giammusso 2017; Iwamura 2015; Kaplan 2004; Lee 2006a; Macchione 2017; Maurizi 2019; Morgia 2010; Morgia 2017; Okada 1985; Park 2005; Reissigl 2004; Shoskes 1999; Wagenlehner 2009; Xu 2000; Ye 2006).
Botulinum toxin A (Elshawaf 2009; Falahatkar 2015; Gottsch 2011).
Allopurinol (Persson 1996; Ziaee 2006).
Traditional Chinese medicine (Chen 2009; Hu 2015; Li 2003; Li 2007; Li 2012; Peng 2003; Shi 1994; Sun 2008; Tan 2009; Wang 2004; Xia 2014; Zhang 2007).
Other pharmacological agents

- Anticholinergics agents (Kim 2008; Kim 2011b)
- Antidepressant (Giannantoni 2014; Lee 2005; Turkington 2002; Zhang 2017)
- Mepartricin (Cavallini 2001; De Rose 2004)
- OM‐89 (Wagenlehner 2014)
- Pentosan (Nickel 2005; Wedren 1987)
- Phosphodiesterase inhibitors (Abdalla 2018; Kong 2014; Lin 2007; Park 2012; Park 2017; Singh 2017)
- Pregabalin (Pontari 2010)
- Tanezumab (Nickel 2016)

Outcomes

Almost all studies reported the effects of the interventions on prostatitis symptoms. All but three studies used the NIH‐CPSI score: two studies (Lee 2005; Leskinen 1999) used a 100‐point validated scale (Prostatitis Symptom Severity Index (PSSI)) and Lacquaniti 1999 used another validated scale (0 to 12, from Neal 1994).

Other secondary outcomes relevant to this review were reported inconsistently. Ten studies did not report prostatitis symptoms: three studies reported global improvement as a composite outcome of symptoms and laboratory findings (Cavallini 2001; Peng 2003; Shi 1994) and seven studies reported clinical improvement using locally‐developed scales (Churakov 2012; Dunzendorfer 1983; Elist 2006; Persson 1996; Wedren 1987; Xu 2000; Okada 1985). Some of these studies provided information about adverse events.

We found mostly short‐term outcomes for the included comparisons. Median follow‐up was eight weeks (interquartile range 6 to 12 weeks; range 4 to 72 weeks).

Funding sources

Most studies (54 studies, 55%) did not specify their funding sources. Seven studies were financed by their local government (Bates 2007; Mehik 2003; Li 2007; Li 2012; Peng 2003; Zhang 2007; Zhao 2019), one study by a non‐governmental organisation (Lee 2005), three studies by universities (Kim 2008; Kong 2014; Ryu 2007), six studies received mixed financing from government and pharmaceutical companies (Alexander 2004; Lu 2004; Nickel 2003a; Nickel 2004a; Nickel 2008; Pontari 2010) and 15 studies were funded by pharmaceutical companies (Cheah 2003; Dunzendorfer 1983; Elist 2006; Goldmeier 2005; Jung 2006; Maurizi 2019; Nickel 2003b; Nickel 2004b; Nickel 2005; Nickel 2011a; Nickel 2016; Turkington 2002; Wagenlehner 2009; Wagenlehner 2014; Ye 2008). Thirteen studies specified that they had no funding (Abdalla 2018; Apolikhin 2010; Breusov 2014; Churakov 2012; Leskinen 1999; Morgia 2017; Macchione 2017; Sivkov 2005; Park 2012; Reissigl 2004; Singh 2017; Wang 2016; Zhang 2017).

Excluded studies

We excluded 54 studies for the following reasons (see Characteristics of excluded studies).

Twelve studies evaluated an ineligible participant population: eight studies included participants with bacterial prostatitis, but with no disaggregated data for CP/CPPS (Barbalias 1998; Chen 2016; Feng 2011; Galeone 2012; Glybochko 2014; Golubchikov 2005; Lokshin 2010; Pushkar' 2006; Simmons 1985) and three studies did not use the NIH criteria for CP/CPPS (Minjie 2017; Nickel 2011b; Zhang 2011)

We found 31 studies to have an ineligible study design: 27 studies specified that they did not use randomisation or used a non‐random sequence for the allocation of participants (Abdel‐Meguid 2018; Aliaev 2006; Allen 2017; Colleen 1975; DRKS00009352; Evliyaoğlu 2002; Hong 2008; Ikeuchi 1990; ISRCTN43221600; Kalinina 2015; Kamalov 2006; Kogan 2010; Lee 2006b; Leng 2007; Lopatkin 2009; Loran 2003; Ma 2015; Nishino 2017; Osborn 1981; Pavone 2010; Razumov 2005; Stamatiou 2014; Takahashi 2005; Thin 1983; Tkachuk 2006; Tkachuk 2011; Xu 2004); two studies reported the follow‐up of a single arm of a randomised controlled trial (Kotarinos 2009; Marx 2013); one study was a non‐controlled study of different routes of administration of an intervention (El‐enen 2015), and one study was a phase II dose‐finding study with an adaptive design (Wagenlehner 2017).

Additionally, 11 studies were terminated and no outcome data were available, due to problems in their conduct (Bschleipfer 2007; NCT02042651; NCT00194597; NCT00194623; NCT03500159; NCT00194636; NCT00301405; NCT00464373; NCT00529386; NCT01678911; NCT01830829).

Risk of bias in included studies

See Figure 2 for a summary of 'Risk of bias' assessments. See Figure 3 for the individual assessments of the included studies. Detailed descriptions of the supporting judgements can be found in the Characteristics of included studies. Considering a global assessment of risk of bias for the main outcomes of this review, only three studies had low risk of bias (Alexander 2004; Nickel 2004b; Pontari 2010), 23 studies had unclear risk of bias (Breusov 2014; Cha 2009; Chen 2011; Cheng 2010; Elist 2006; Elshawaf 2009; Abdalla 2018; Falahatkar 2015; Jung 2006; Kim 2008; Lacquaniti 1999; Li 2003; Mo 2006; Nickel 2003a; Nickel 2011a; Park 2012; Reissigl 2004; Ryu 2007; Yang 2009; Yang 2010; Ye 2006; Youn 2008; Ziaee 2006) and the remaining 70 studies had at least one domain with high risk of bias.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

Random sequence generation

Thirty‐one studies specified an adequate method of random sequence allocation (Alexander 2004; Breusov 2014; Cai 2014; Cai 2017; Cheah 2003; Chen 2011; Choe 2014; De Rose 2004; Dunzendorfer 1983; Elist 2006; Goldmeier 2005; Gottsch 2011; Hu 2015; Lacquaniti 1999; Lu 2004; Mehik 2003; Morgia 2010; Nickel 2003a; Nickel 2003b; Nickel 2004b; Nickel 2008; Nickel 2016; Persson 1996; Pontari 2010; Singh 2017; Tan 2009; Turkington 2002; Wagenlehner 2009; Wagenlehner 2014; Wang 2016; Zhao 2009). The remaining studies were at unclear risk of bias for random sequence generation.

Allocation concealment

Twenty‐two studies specified an adequate method of allocation concealment (Alexander 2004; Bates 2007; De Rose 2004; Elist 2006; Falahatkar 2015; Goldmeier 2005; Gottsch 2011; Iwamura 2015; Mehik 2003; Morgia 2010; Nickel 2003a; Nickel 2003b; Nickel 2004b; Nickel 2008; Nickel 2011a; Nickel 2016; Okada 1985; Persson 1996; Pontari 2010; Singh 2017; Wagenlehner 2009; Wagenlehner 2014). One study specified that they did not conceal the allocation of participants and was deemed at high risk of bias for this domain (Choe 2014). The remaining studies were at unclear risk of bias in allocation concealment.

Blinding

Selective reporting

Ten studies had low risk of reporting bias when comparing their outcomes to their protocols or trial registrations (Alexander 2004; Falahatkar 2015; Iwamura 2015; Nickel 2003a; Nickel 2004b; Nickel 2008; Nickel 2011a; Pontari 2010; Wagenlehner 2014; Wang 2016). Twenty studies reported some of their outcomes graphically or with missing data and were deemed at high risk of bias (Apolikhin 2010; Bates 2007; Choe 2014; Churakov 2012; Erdemir 2010; Giammusso 2017; Kaplan 2004; Kim 2003; Kulovac 2007; Lee 2006a; Leskinen 1999; Mehik 2003; Morgia 2010; Nickel 2003b; Nickel 2016; Persson 1996; Wagenlehner 2009; Wang 2004; Zhao 2009; Zhou 2008). The remaining studies were at unclear risk of reporting bias.

Other potential sources of bias

Four studies were at high risk of bias for this domain: in two studies (Nickel 2016; Wagenlehner 2009), the pharmaceutical company participated in the conduct and publication of the study: in one study there were large baseline difference between groups (Park 2005), and in another study an active run‐in phase was implemented (Ye 2008). Nineteen studies were at unclear risk of bias for this domain: eight studies had insufficient data to make a judgement, since they were available as abstract only (Abdalla 2018; Cheng 2010; Elshawaf 2009; Macchione 2017; Park 2012; Park 2017; Reissigl 2004; Singh 2017), nine studies reported baseline characteristics poorly or they were not available (Giammusso 2017; Kim 2003; Kim 2011a; Kim 2011b; Kulovac 2007; Sivkov 2005; Tugcu 2006; Zhao 2009; Zhou 2008), one sturdy reported small differences in baseline characteristics (Kong 2014), and two studies provided no information about how many participants were in each group (Lacquaniti 1999; Morgia 2010). The remaining studies were at low risk of other bias.

Effects of interventions

See: Table 1; Table 2; Table 3; Table 4; Table 5; Table 6; Table 7; Table 8

Summary of findings for the main comparison. Alpha blockers compared to placebo for chronic prostatitis/chronic pelvic pain syndrome.

Alpha blockers compared to placebo for chronic prostatitis/chronic pelvic pain syndrome
Patient or population: men with chronic prostatitis/chronic pelvic pain syndrome  Setting: outpatient, single‐centre and multicentre studies in Bosnia and Herzegovina, Canada, China, USA, Finland, Germany, Malaysia, Russia, South Korea and Turkey  Intervention: alpha blockers (terazosin, doxazosin, phenoxybenzamine, tamsulosin, alfuzosin, silodosin)  Comparison: placebo or no intervention Some comparisons included alpha blockers as add‐on therapy to medical therapy (e.g. antibiotics) versus medical therapy alone.
Outcomes	№ of participants  (studies)  Follow‐up	Quality of the evidence  (GRADE)	Relative effect  (95% CI)	*Anticipated absolute effects^ (95% CI)**
				Risk with placebo	Risk difference with alpha‐blockers
Prostatitis symptoms  Assessed with: NIH‐CPSI score. Benefit is indicated by lower scores  Scale from: 0 to 43  Follow‐up: range 6 weeks to 6 months A decrease of 25% or 6 points is considered an important improvement	1524  (18 RCTs)	⊕⊝⊝⊝  VERY LOW^a,b,c	‐	The mean prostatitis symptoms ranged from 12.1 to 24.14	MD 5.01 lower  (7.41 lower to 2.61 lower)
Prostatitis symptoms  Assessed with: NIH‐CPSI score. Benefit is indicated by lower scores  Scale from: 0 to 43  Follow‐up: 12 months	253 (4 RCTs)	⊕⊝⊝⊝  VERY LOW^a,b,c	‐	The mean prostatitis symptoms ranged from 18.7 to 22.24	MD 5.6 lower  (10.89 lower to 0.82 lower)
Prostatitis symptoms: 'responders'  Number of participants with a 25% or 6‐point decrease in NIH‐CPSI scores  Follow‐up: range 6 weeks to 6 months	721  (7 RCTs)	⊕⊝⊝⊝  VERY LOW^a,b,c	RR 1.23  (0.94 to 1.61)	Study population
				477 per 1000	110 more per 1000  (29 fewer to 291 more)
Adverse events Any adverse event  Follow‐up: range 6 weeks to 6 months	1588  (19 RCTs)	⊕⊕⊝⊝  LOW^a,c	RR 1.60  (1.09 to 2.34)	Study population
				94 per 1000	56 more per 1000  (8 more to 126 more)
Sexual dysfunction  Assessed with: International Index of Erectile Function Scale. Benefit is indicated by higher scores  Scale from: 5 to 25  Follow‐up: range 6 weeks to 12 weeks	452  (4 RCTs)	⊕⊕⊕⊝  MODERATE^a	‐	The mean sexual dysfunction ranged from 16.1 to 18.4	MD 0.26 higher  (1.13 lower to 1.65 higher)
Quality of life  Assessed with: Short Form‐12 Health Status Questionnaire. Benefit is indicated by higher scores. The effect is reported for mental domain.  Scale from: 0 to 100  Follow‐up: range 6 weeks to 12 weeks	421  (3 RCTs)	⊕⊕⊕⊝  MODERATE^a	‐	The mean quality of life ranged from 41 to 46	MD 0.15 higher  (2.63 lower to 2.92 higher)
Anxiety and depression  Assessed with: Hospital Anxiety and Depression Scale. Benefit is indicated by lower scores  Scale from: 0 to 21  Follow‐up: 12 weeks	232  (1 RCT)	⊕⊕⊝⊝  LOW^a,c	‐	The mean anxiety and depression was 12.8	MD 1.1 lower  (2.54 lower to 0.34 higher)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: Confidence interval;MD: Mean difference; NIH‐CPSI: National Institutes of Health ‐ Chronic Prostatitis Symptom Index; RCT: Randomised controlled trial; RR: Risk ratio
GRADE Working Group grades of evidence  High quality: We are very confident that the true effect lies close to that of the estimate of the effect  Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect  Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

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^aDowngraded one level due to study limitations: unclear or high risk of bias in most domains in most studies.  ^bDowngraded one level due to inconsistency: substantial or considerable heterogeneity.  ^cDowngraded one level due to imprecision: confidence interval crosses the assumed threshold for the minimal clinically important difference.

Summary of findings 2. 5‐alpha reductase inhibitors compared to placebo for chronic prostatitis/chronic pelvic pain syndrome.

5‐alpha reductase inhibitors compared to placebo for chronic prostatitis/chronic pelvic pain syndrome
Patient or population: men with chronic prostatitis/chronic pelvic pain syndrome  Setting: outpatient, single‐centre studies in Finland and USA  Intervention: finasteride  Comparison: placebo
Outcomes	№ of participants  (studies)  Follow‐up	Quality of the evidence  (GRADE)	Relative effect  (95% CI)	*Anticipated absolute effects^ (95% CI)**
				Risk with placebo	Risk difference with 5 alpha reductase inhibitors
Prostatitis symptoms  Assessed with: NIH‐CPSI score. Benefit is indicated by lower scores  Scale from: 0 to 43  Follow‐up: 6 months A decrease of 25% or 6 points is considered an important improvement	64  (1 RCT)	⊕⊕⊕⊝  MODERATE^a	‐	The mean prostatitis symptoms was 21.7	MD 4.6 lower  (5.43 lower to 3.77 lower)
Prostatitis symptoms: 'responders'  Number of participants with a 25% decrease in NIH‐CPSI scores  Follow‐up: 6 months	64  (1 RCT)	⊕⊕⊝⊝  LOW^a,b	RR 2.13  (0.82 to 5.53)	Study population
				152 per 1000	171 more per 1000  (27 fewer to 686 more)
Adverse events  Follow‐up: range 6 months to 12 months	105  (2 RCTs)	⊕⊕⊝⊝  LOW^a,b	RR 0.87  (0.33 to 2.30)	Study population
				163 per 1000	21 fewer per 1000  (109 fewer to 212 more)
Sexual dysfunction ‐ not reported	‐	‐	‐	‐	‐
Quality of life ‐ not reported	‐	‐	‐	‐	‐
Anxiety and depression ‐ not reported	‐	‐	‐	‐	‐
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: Confidence interval; NIH‐CPSI: National Institutes of Health ‐ Chronic Prostatitis Symptom Index; RCT: randomised controlled trial; RR: Risk ratio
GRADE Working Group grades of evidence  High quality: We are very confident that the true effect lies close to that of the estimate of the effect  Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect  Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

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^aDowngraded one level due to high risk of bias: unclear or high risk of bias in most domains in the main study of this comparison.  ^bDowngraded one level due to imprecision: confidence interval includes appreciable benefits and harms.

Summary of findings 3. Antibiotic therapy compared to placebo for chronic prostatitis/chronic pelvic pain syndrome.

Antibiotic therapy compared to placebo for chronic prostatitis/chronic pelvic pain syndrome
Patient or population: men with chronic prostatitis/chronic pelvic pain syndrome  Setting: outpatient, single‐centre and multicentre studies in USA, Canada, South Korea, Bosnia and Herzegovina and China  Intervention: antibiotic therapy (ciprofloxacin or levofloxacin)  Comparison: placebo Some comparisons included antibiotics as add‐on therapy to medical therapy (e.g. alpha blockers) versus medical therapy alone
Outcomes	№ of participants  (studies)  Follow‐up	Quality of the evidence  (GRADE)	Relative effect  (95% CI)	*Anticipated absolute effects^ (95% CI)**
				Risk with placebo	Risk difference with antibiotic therapy
Prostatitis symptoms  Assessed with: NIH‐CPSI score. Benefit is indicated by lower scores  Scale from: 0 to 43  Follow‐up: range 6 weeks to 3 months A decrease of 25% or 6 points is considered an important improvement	372  (5 RCTs)	⊕⊕⊝⊝  LOW^a,b	‐	The mean prostatitis symptoms ranged from 8.6 to 18.2	MD 2.43 lower  (4.72 lower to 0.15 lower)
Prostatitis symptoms: 'responders'  Number of participants with a 25% or 6‐point decrease in NIH‐CPSI scores  Follo‐up: range 6 weeks to 3 months	178  (2 RCTs)	⊕⊕⊝⊝  LOW^b,c	RR 1.12  (0.73 to 1.74)	Study population
				286 per 1000	34 more per 1000  (77 fewer to 211 more)
Adverse events  Follow‐up: range 3 weeks to 6 months	336  (4 RCTs)	⊕⊕⊕⊝  MODERATE^c,d	RR 1.01  (0.66 to 1.55)	Study population
				213 per 1000	2 more per 1000  (72 fewer to 117 more)
Sexual dysfunction  Assessed with: International Index of Erectile Function Scale. Benefit is indicated by higher scores  Scale from: 5 to 25  Follow‐up: 6 weeks	77  (1 RCT)	⊕⊕⊕⊝  MODERATE^b	‐	The mean sexual dysfunction was 16.8	MD 0.4 higher  (1.59 lower to 2.39 higher)
Quality of life  Assessed with: SF‐12 Health Status Questionnaire. Benefit is indicated by higher scores. The effect is reported for mental domain  Scale from: 0 to 100  Follow up: 6 weeks	87  (1 RCT)	⊕⊕⊕⊝  MODERATE^c	‐	The mean quality of life was 44.3	MD 3.9 lower  (7.94 lower to 0.14 higher)
Anxiety and depression ‐ not reported	‐	‐	‐	‐	‐
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: Confidence interval; NIH‐CPSI: National Institutes of Health ‐ Chronic Prostatitis Symptom Index; RCT: randomised controlled trial; RR: Risk ratio;
GRADE Working Group grades of evidence  High quality: We are very confident that the true effect lies close to that of the estimate of the effect  Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect  Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

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^aDowngraded one level due to inconsistency: statistical heterogeneity 75%.  ^bDowngraded one level due to high risk of bias: unclear or high risk of bias in most domains in the main study of this comparison.  ^cDowngraded one level due to imprecision: confidence interval crosses the threshold for the minimal clinically important difference.  ^dWe did not downgrade for risk of bias since the main study contributing to this estimate has low risk of bias.

Summary of findings 4. Anti‐inflammatories compared to control for chronic prostatitis/chronic pelvic pain syndrome.

Anti‐inflammatories compared to placebo for chronic prostatitis/chronic pelvic pain syndrome
Patient or population: men with chronic prostatitis/chronic pelvic pain syndrome  Setting: outpatient, single‐centre and multicentre studies in UK, South Korea, Turkey, China  Intervention: anti‐inflammatories (non‐steroidal anti‐inflammatories, corticosteroids, antileukotrienes, tiocolchicoside)  Comparison: placebo
Outcomes	№ of participants  (studies)  Follow‐up	Quality of the evidence  (GRADE)	Relative effect  (95% CI)	*Anticipated absolute effects^ (95% CI)**
				Risk with control	Risk difference with anti‐inflammatories
Prostatitis symptoms  Assessed with: NIH‐CPSI score. Benefit is indicated by lower scores  Scale from: 0 to 43  Follow‐up: range 6 weeks to 6 months A decrease of 25% or 6 points is considered an important improvement	585  (7 RCTs)	⊕⊕⊝⊝  LOW^a,b	‐	The mean prostatitis symptoms ranged from 8.6 to 19.5	MD 2.5 lower  (3.74 lower to 1.26 lower)
Prostatitis symptoms: 'responders'  Number of participants with a 25% or 6‐point decrease in NIH‐CPSI scores  Follow‐up: range 8 weeks to 3 months	82  (2 RCTs)	⊕⊕⊝⊝  LOW^a,c	RR 1.44  (0.68 to 3.03)	Study population
				91 per 1000	40 more per 1000  (29 fewer to 185 more)
Adverse events  Follow‐up: range 4 weeks to 6 months	540  (7 RCTs)	⊕⊕⊝⊝  LOW^a,c	RR 1.27  (0.81 to 2.00)	Study population
				98 per 1000	26 more per 1000  (19 fewer to 98 more)
Sexual dysfunction ‐ not reported	‐	‐	‐	‐	‐
Quality of life ‐ not reported	‐	‐	‐	‐	‐
Anxiety and depression ‐ not reported	‐	‐	‐	‐	‐
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: Confidence interval; NIH‐CPSI: National Institutes of Health ‐ Chronic Prostatitis Symptom Index; RCT: randomised controlled trial; RR: Risk ratio;
GRADE Working Group grades of evidence  High quality: We are very confident that the true effect lies close to that of the estimate of the effect  Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect  Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

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^aDowngraded one level due to high risk of bias: unclear or high risk of bias in most domains in most studies.  ^bDowngraded one level due to inconsistency: high statistical heterogeneity (> 80%).  ^cDowngraded one level due to imprecision: confidence interval crosses the threshold for the minimal clinically important difference.

Summary of findings 5. Phytotherapy compared to placebo or other agents for chronic prostatitis/chronic pelvic pain syndrome.

Phytotherapy compared to placebo for chronic prostatitis/chronic pelvic pain syndrome
Patient or population: men with chronic prostatitis/chronic pelvic pain syndrome  Setting: outpatient, single‐centre and multicentre studies in Russia, USA, Italy, South Korea, Germany and China  Intervention: phytotherapeutics agents (pollen extract, calendula‐curcuma, Prolit Super Septo®, flavonoids and cranberries)  Comparison: placebo
Outcomes	№ of participants  (studies)  Follow‐up	Quality of the evidence  (GRADE)	Relative effect  (95% CI)	*Anticipated absolute effects^ (95% CI)**
				Risk with placebo or other agents	Risk difference with phytotherapy
Prostatitis symptoms  Assessed with: NIH‐CPSI score. Benefit is indicated by lower scores  Scale from: 0 to 43  Follow‐up: range 1 month to 3 months A decrease of 25% or 6 points is considered an important improvement	320  (5 RCTs)	⊕⊕⊝⊝  LOW^a,b	‐	The mean prostatitis symptoms ranged from 10.3 to 14.5	MD 5.02 lower  (6.81 lower to 3.23 lower)
Prostatitis symptoms: 'responders'  Number of participants with a 25% or 6‐point decrease in NIH‐CPSI scores  Follow‐up: range 1 month to 3 months	224  (3 RCTs)	⊕⊕⊕⊝  MODERATE^a	RR 1.78  (1.25 to 2.52)	Study population
				384 per 1000	299 more per 1000  (96 more to 584 more)
Adverse events  Follow‐up: range 1 month to 3 months	540  (7 RCTs)	⊕⊕⊝⊝  LOW^a,c	RR 1.13  (0.54 to 2.36)	Study population
				41 per 1000	5 more per 1000  (19 fewer to 56 more)
Sexual dysfunction  Assessed with: International Index of Erectile Function Scale Benefit is indicated by higher scores  Scale from: 5 to 25  Follow‐up: 3 months	48  (1 RCT)	⊕⊕⊝⊝  LOW^a,b	‐	The mean sexual dysfunction was 18.5	MD 3.5 higher  (2.67 higher to 4.33 higher)
Quality of life ‐ not reported	‐	‐	‐	‐	‐
Anxiety and depression ‐ not reported	‐	‐	‐	‐	‐
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: Confidence interval; NIH‐CPSI: National Institutes of Health ‐ Chronic Prostatitis Symptom Index; RCT: randomised controlled trial; RR: Risk ratio;
GRADE Working Group grades of evidence  High quality: We are very confident that the true effect lies close to that of the estimate of the effect  Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect  Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

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^aDowngraded one level due to high risk of bias: unclear or high risk of bias in most domains in most studies.  ^bDowngraded one level due to imprecision: confidence interval crosses the threshold for the minimal clinically important difference.  ^cDowngraded one level due to imprecision: few events, resulting in a confidence interval that includes appreciable benefits and harms.

Summary of findings 6. Botulinum toxin A compared to placebo for chronic prostatitis/chronic pelvic pain syndrome.

Botulinum toxin A compared to placebo for chronic prostatitis/chronic pelvic pain syndrome
Patient or population: men with chronic prostatitis/chronic pelvic pain syndrome  Setting: outpatient,outpatient, single‐centre studies in Iran and USA  Intervention: botulinum toxin A injection (intraprostatic or pelvic floor muscles)  Comparison: sham procedure (saline injection)
Outcomes	№ of participants  (studies)  Follow‐up	Quality of the evidence  (GRADE)	Relative effect  (95% CI)	*Anticipated absolute effects^ (95% CI)**
Outcomes	№ of participants  (studies)  Follow‐up	Quality of the evidence  (GRADE)	Relative effect  (95% CI)	Risk with placebo	Risk difference with botulinum toxin A
Prostatitis symptoms Subgroup: Intraprostatic injection, participants age > 50 years old, basal NIH‐CPSI score > 30 Assessed with: NIH‐CPSI score. Benefit is indicated by lower scores  Scale from: 0 to 43  Follow‐up: 6 months A decrease of 25% or 6 points is considered an important improvement	60  (1 RCT)	⊕⊕⊝⊝  LOW^a,b	‐	The mean prostatitis symptoms ‐ Intraprostatic injection was 36.37	MD 25.8 lower  (30.15 lower to 21.45 lower)
Prostatitis symptoms Subgroup: Pelvic floor muscles injection, participants age < 50 years old, basal NIH‐CPSI score < 30  Assessed with: NIH‐CPSI score. Benefit is indicated by lower scores  Scale from: 0 to 43  Follow‐up: 1 month	29  (1 RCT)	⊕⊕⊝⊝  LOW^b,c	‐	The mean prostatitis symptoms ‐ Pelvic floor muscles injection was 27.8	MD 2.6 lower  (5.59 lower to 0.39 higher)
Adverse events  Assessed with: e.g.: haematuria  Follow‐up: range 1 month to 6 months	89  (2 RCTs)	⊕⊕⊝⊝  LOW^d,e	RR 5.00  (0.25 to 99.95)	Study population
	89  (2 RCTs)	⊕⊕⊝⊝  LOW^d,e	RR 5.00  (0.25 to 99.95)	22 per 1000	87 more per 1000  (16 fewer to 2.151 more)
Sexual dysfunction ‐ not reported	‐	‐	‐	‐	‐
Quality of life ‐ not reported	‐	‐	‐	‐	‐
Anxiety and depression ‐ not reported	‐	‐	‐	‐	‐
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: Confidence interval; NIH‐CPSI: National Institutes of Health ‐ Chronic Prostatitis Symptom Index; RCT: randomised controlled trial; RR: Risk ratio
GRADE Working Group grades of evidence  High quality: We are very confident that the true effect lies close to that of the estimate of the effect  Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect  Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

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^aDowngraded one level due to unclear risk of bias (random sequence generation).  ^bDowngraded one level due to imprecision: small sample size resulting in wide confidence interval.  ^cDowngraded one level due to high risks of performance and detection bias,  ^dDowngraded one level due to high risk of bias: unclear or high risks of bias in some domains.  ^eDowngraded one level due to imprecision: few events. The number of adverse events was zero in the control group, but one case was imputed in this group in order to obtain the relative estimates.

Summary of findings 7. Allopurinol compared to placebo for chronic prostatitis/chronic pelvic pain syndrome.

Allopurinol compared to placebo for chronic prostatitis/chronic pelvic pain syndrome
Patient or population: men with chronic prostatitis/chronic pelvic pain syndrome  Setting: outpatient, single‐centre studies in Sweden and Iran  Intervention: allopurinol  Comparison: placebo
Outcomes	№ of participants  (studies)  Follow‐up	Quality of the evidence  (GRADE)	Relative effect  (95% CI)	*Anticipated absolute effects^ (95% CI)**
Outcomes	№ of participants  (studies)  Follow‐up	Quality of the evidence  (GRADE)	Relative effect  (95% CI)	Risk with placebo	Risk difference with allopurinol
Prostatitis symptoms  Assessed with: NIH‐CPSI score. Benefit is indicated by lower scores  Scale from: 0 to 43  Follow‐up: 3 months A decrease of 25% or 6 points is considered an important improvement	56  (1 RCT)	⊕⊕⊝⊝  LOW^a,b	‐	The mean prostatitis symptoms was 17.21	MD 0.21 lower  (4.48 lower to 4.06 higher)
Adverse events Follow‐up: 3 months	110  (2 RCTs)	⊕⊕⊝⊝  LOW^b,c	‐	No adverse events were observed in the included studies
Sexual dysfunction ‐ not reported	‐	‐	‐	‐	‐
Quality of life ‐ not reported	‐	‐	‐	‐	‐
Anxiety and depression ‐ not reported	‐	‐	‐	‐	‐
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: Confidence interval; NIH‐CPSI: National Institutes of Health ‐ Chronic Prostatitis Symptom Index; RCT: randomised controlled trial; RR: Risk ratio
GRADE Working Group grades of evidence  High quality: We are very confident that the true effect lies close to that of the estimate of the effect  Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect  Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

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^aDowngraded one level due to imprecision: confidence interval includes appreciable benefits and harms.˜  ^bDowngraded one level due to high risk of bias: unclear or high risks of bias in the main study of this comparison.  ^cDowngraded one level due to imprecision: few events (zero events).

Summary of findings 8. Traditional Chinese Medicine compared to placebo or usual care for chronic prostatitis/chronic pelvic pain syndrome.

Traditional Chinese Medicine compared to placebo for chronic prostatitis/chronic pelvic pain syndrome
Patient or population: men with chronic prostatitis/chronic pelvic pain syndrome  Setting: outpatient, single‐centre studies in China  Intervention: Traditional Chinese Medicine (herbs decoctions, capsules and suppositories)  Comparison: placebo Some comparisons included antibiotics, alpha blockers and other Western medications as co‐interventions
Outcomes	№ of participants  (studies)  Follow‐up	Quality of the evidence  (GRADE)	Relative effect  (95% CI)	*Anticipated absolute effects^ (95% CI)**
Outcomes	№ of participants  (studies)  Follow‐up	Quality of the evidence  (GRADE)	Relative effect  (95% CI)	Risk with placebo or usual care	Risk difference with Traditional Chinese medicine
Prostatitis symptoms  Assessed with: NIH‐CPSI score. Benefit is indicated by lower scores  Scale from: 0 to 43  Follow‐up: range 2 weeks to 2 months A decrease of 25% or 6 points is considered an important improvement	835  (7 RCTs)	⊕⊕⊝⊝  LOW^a,b	‐	The mean prostatitis symptoms ranged from 11.17 to 15.02	MD 3.13 lower  (4.99 lower to 1.28 lower)
Adverse events  Follow‐up: range 4 weeks to 8 weeks	584  (4 RCTs)	⊕⊕⊝⊝  LOW^b,c	RR 1.34  (0.22 to 8.02)	Study population
Adverse events  Follow‐up: range 4 weeks to 8 weeks	584  (4 RCTs)	⊕⊕⊝⊝  LOW^b,c	RR 1.34  (0.22 to 8.02)	29 per 1000	10 more per 1000  (23 fewer to 203 more)
Sexual dysfunction  Assessed with: International Index of Erectile Function Scale. Benefit is indicated by higher scores  Scale from: 5 to 25  Follow‐up: 2 weeks	88  (1 RCT)	⊕⊕⊕⊝  MODERATE^b	‐	The mean sexual dysfunction was 14.93	MD 0.27 higher  (1.17 lower to 1.71 higher)
Quality of life ‐ not reported	‐	‐	‐	‐	‐
Anxiety and depression: anxiety  Assessed with: Hamilton Anxiety Rating Scale (HAM‐A)  Scale from: 0 to 56  Follow‐up: 2 weeks	88  (1 RCT)	⊕⊕⊝⊝  LOW ^{2 4}	‐	The mean anxiety and depression: anxiety was 23.3	MD 9.5 lower  (11.7 lower to 7.3 lower)
Anxiety and depression: depression  Assessed with: Hamilton Depression Rating Scale (HAM‐D)  Scale from: 0 to 54  Follow‐up: 2 weeks	88  (1 RCT)	⊕⊕⊝⊝  LOW^b,d	‐	The mean anxiety and depression: depression was 24.07	MD 7.84 lower  (10.71 lower to 4.97 lower)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: Confidence interval; NIH‐CPSI: National Institutes of Health ‐ Chronic Prostatitis Symptom Index; RCT: randomised controlled trial; RR: Risk ratio
GRADE Working Group grades of evidence  High quality: We are very confident that the true effect lies close to that of the estimate of the effect  Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect  Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

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^aDowngraded one level due to inconsistency: high statistical heterogeneity (> 80%). Some of this inconsistency might be explained by the differences between the interventions under this comparison.  ^bDowngraded one level due to high risk of bias: unclear or high risks of bias in most domains in most studies.  ^cDowngraded one level due to imprecision: few events, resulting in a confidence interval that includes appreciable benefits and harms.  ^dDowngraded one level due to imprecision: small sample size resulting in wide confidence interval that crosses the threshold for the minimal clinically important difference.

Unless stated otherwise, mean differences in prostatitis symptoms refer to NIH‐CPSI scores and the responder rate refers to the number of participants who achieved a six‐point decrease or a 25% decrease in NIH‐CPSI scores (See Types of outcome measures). Other outcome measurements may vary. The number of participants under each comparison represent the total number of randomized participants, whereas the number of participants for each outcome are those analysed.

1. Alpha blockers versus placebo

Twenty‐four studies with 2387 randomized participants compared the use of alpha blockers versus placebo or no additional treatment (Alexander 2004; Cha 2009; Cheah 2003; Chen 2011; Dunzendorfer 1983; Erdemir 2010; Gül 2001; Jeong 2008; Jung 2006; Kim 2003; Kulovac 2007; Lu 2004; Mehik 2003; Mo 2006; Nickel 2004b; Nickel 2008; Nickel 2011a; Ryu 2007; Sivkov 2005; Tuğcu 2007; Wang 2016; Wu 2008; Yang 2010; Youn 2008). See Table 9 and Table 10 for further details of the participants and interventions. See Table 1. Three studies were not included in this summary due to missing data and are described below (Cha 2009; Gül 2001;Lacquaniti 1999). We used data from Cha 2009 for the outcome of adverse events.

1.1.1. Prostatitis symptoms: short‐term

Based on 18 studies with 1524 participants with a six‐week to six‐month follow‐up (Alexander 2004; Cheah 2003; Chen 2011; Erdemir 2010; Jung 2006; Kim 2003; Kulovac 2007; Lu 2004; Mehik 2003; Mo 2006; Nickel 2008; Nickel 2011a; Ryu 2007; Tuğcu 2007; Wang 2016; Wu 2008; Yang 2009; Youn 2008), we are uncertain of the effects of alpha blockers on prostatitis symptoms compared to placebo or to no additional treatment (random‐effects meta‐analysis; MD −5.01, 95% CI −7.41 to −2.61; I² = 98%; Analysis 1.1). These lower scores were observed across all subscores of pain, urinary symptoms and QoL (Analysis 1.2; Analysis 1.3; Analysis 1.4). The quality of evidence was very low, due to study limitations, inconsistency (high statistical heterogeneity) and imprecision. We could not identify asymmetry in the funnel plot suggestive of publication bias (see Figure 4).

1.1 — Comparison 1 Alpha‐blockers versus placebo, Outcome 1 Prostatitis symptoms: short term.

1.2 — Comparison 1 Alpha‐blockers versus placebo, Outcome 2 Prostatitis symptoms: pain.

1.3 — Comparison 1 Alpha‐blockers versus placebo, Outcome 3 Prostatitis symptoms: urinary.

1.4 — Comparison 1 Alpha‐blockers versus placebo, Outcome 4 Prostatitis symptoms: quality of life.

Funnel plot of comparison: 1 Alpha‐blockers versus placebo, outcome: 1.1 Prostatitis symptoms: short term.

Based on seven studies with 721 participants reported (Alexander 2004; Chen 2011; Jeong 2008; Mehik 2003; Nickel 2004b; Nickel 2008; Nickel 2011a), we are uncertain of the effects of alpha blockers in the responders rate compared to placebo or to no additional treatment (random‐effects meta‐analysis; RR 1.23, 95% CI 0.94 to 1.61; I² = 66%; Analysis 1.5). The quality of evidence was very low, due to unclear or high risk of bias in most domains in most studies, inconsistency (high statistical heterogeneity) and imprecision (a confidence interval that crosses the minimal clinically important difference (MCID)).

1.5 — Comparison 1 Alpha‐blockers versus placebo, Outcome 5 Prostatitis symptoms: responders rate.

We found that four studies (Ryu 2007; Tuğcu 2007; Wu 2008; Yang 2010) had standard deviation (SD) values close to one, which is unusual in a body of research in which this value is close to six. We contacted study authors to clarify if this was an error (e.g. if they were the standard error instead of standard deviation), but we received no response.

1.1.2. Prostatitis symptoms: long‐term

Based on four studies with 235 participants with one‐year follow‐up (Erdemir 2010; Mehik 2003; Sivkov 2005; Tuğcu 2007), we are uncertain of the effects of alpha blockers on prostatitis symptoms compared to placebo or to no additional treatment, measured by NIH‐CPSI score (random‐effects meta‐analysis; MD −5.60, 95% CI −10.89 to −0.32; I² = 98%; Analysis 1.6). The quality of the evidence was very low due to unclear or high risk of bias in most domains in most studies, inconsistency (high statistical heterogeneity) and imprecision (the confidence interval crosses the threshold for the MCID).

1.6 — Comparison 1 Alpha‐blockers versus placebo, Outcome 6 Prostatitis symptoms: long term.

Based on one study with 92 participants (Chen 2011), alpha blockers may have result in a small increase in the responders rate compared to placebo or to no additional treatment (RR 1.57, 95% CI 1.06 to 2.32; Analysis 1.7). The quality of evidence was low, due to unclear risk of bias and imprecision (the confidence interval crosses the threshold for the MCID).

1.7 — Comparison 1 Alpha‐blockers versus placebo, Outcome 7 Prostatitis symptoms: long term.

1.2. Adverse events

Based on 19 studies with 1588 participants (Alexander 2004; Cha 2009; Cheah 2003; Chen 2011; Dunzendorfer 1983; Erdemir 2010; Gül 2001; Jeong 2008; Kim 2003; Mo 2006; Nickel 2004b; Nickel 2008; Nickel 2011a; Ryu 2007; Sivkov 2005; Tuğcu 2007; Wang 2016; Wu 2008; Yang 2010), we found that participants who received alpha blockers may experience more adverse events (RR 1.60, 95% CI 1.09 to 2.34; I² = 48%; Analysis 1.8) compared to those who received placebo or no additional intervention at six‐week to six‐month follow‐up. The quality of the evidence is low, due to unclear or high risk of bias in most domains in most studies, and imprecision (the confidence interval crosses the threshold for the MCID). We could not identify asymmetry in the funnel plot suggestive of publication bias (see Figure 5). Common adverse events included: dizziness, hypotension, palpitations, retrograde ejaculation, headache, and heartburn.

1.8 — Comparison 1 Alpha‐blockers versus placebo, Outcome 8 Adverse events.

Funnel plot of comparison: 1 Alpha‐blockers versus placebo, outcome: 1.8 Adverse events.

1.3. Sexual dysfunction

Based on four studies with 452 participants (Chen 2011; Nickel 2008; Ryu 2007; Wang 2016), alpha blockers probably result in little to no difference in sexual dysfunction, measured by IIEF scale at six‐ to 12‐week follow‐up (MD 0.26, 95% CI −1.13 to 1.65; I² = 0%, Analysis 1.9). The quality of the evidence was moderate, due to an unclear or high risk of bias in most domains in most studies.

1.9 — Comparison 1 Alpha‐blockers versus placebo, Outcome 9 Sexual dysfunction.

1.4. Quality of life

Based on three studies with 421 participants (Alexander 2004; Nickel 2008; Nickel 2011a), alpha blockers probably result in little to no difference in quality of life, measured by SF‐12 Health Status Questionnaire at six‐ to 12‐week follow‐up (mental domain MD 0.15, 95% CI −2.63 to 2.92; I² = 51%; Analysis 1.10; physical domain MD 1.17, 95% CI −0.97 to 3.30; I² = 47%, Analysis 1.11). The quality of the evidence was moderate, due to unclear or high risk of bias in some of the included studies.

1.10 — Comparison 1 Alpha‐blockers versus placebo, Outcome 10 Quality of life: mental.

1.11 — Comparison 1 Alpha‐blockers versus placebo, Outcome 11 Quality of life: physical.

1.5. Anxiety and depression

Based on one study with 232 participants (Nickel 2008), alpha blockers probably result in little to no difference in anxiety and depression, measured by the Hospital Anxiety and Depression Scale at 12‐week follow‐up (MD −1.10, 95% CI −2.54 to 0.34; Analysis 1.12). The quality of evidence was low, due to high risk of attrition bias and imprecision (the confidence interval crosses the threshold for the MCID).

1.12 — Comparison 1 Alpha‐blockers versus placebo, Outcome 12 Anxiety and depression.

1.6. Urinary symptoms

Based on two studies with 143 participants (Cheah 2003; Ryu 2007), we are uncertain of the effect of alpha blockers on urinary symptoms compared to placebo or to no additional treatment, measured by IPSS at 12‐ to 14‐week follow‐up (MD −2.68, 95% CI −5.90 to 0.54; I² = 88%; Analysis 1.13). The quality of evidence was very low, due to study limitations, inconsistency and imprecision.

1.13 — Comparison 1 Alpha‐blockers versus placebo, Outcome 13 Urinary symptoms.

Sensitivity analysis: risk of bias

Prostatitis symptoms

Excluding all studies with unclear or high risk of bias, we included only two studies with 153 participants under this comparison (Alexander 2004; Nickel 2004b). One of these studies (Alexander 2004) indicated that there was little to no difference in prostatitis symptoms between those who received tamsulosin or placebo, (MD −1.00, 95% CI −3.35 to 1.35, I² = 0%). When analysing the number of responders, only two studies with 155 participants were included under this comparison (Alexander 2004; Nickel 2004b). Tamsulosin made little to no difference in the responder rate (RR 1.16, 95% CI 0.73 to 1.82; I² = 0%; Analysis 1.14).

1.14 — Comparison 1 Alpha‐blockers versus placebo, Outcome 14 Prostatitis symptoms: responders rate (sensitivity analysis according to risk of bias).

Adverse events

Excluding all studies with unclear or high risk of bias, we included only two studies with 153 participants under this comparison (Alexander 2004; Nickel 2004b). Tamsulosin made little to no difference in the incidence of adverse events (random‐effects meta‐analysis: RR 0.96, 95% CI 0.63 to 1.47, I² = 0%; Analysis 1.15).

1.15 — Comparison 1 Alpha‐blockers versus placebo, Outcome 15 Adverse events (sensitivity analysis according to risk of bias).

Sensitivity analysis: diagnostic criteria

We performed a sensitivity analysis excluding Dunzendorfer 1983, which did not meet the Research Consensus definition for CP/CPPS (Nickel 1999).

Prostatitis symptoms

The exclusion of Dunzendorfer 1983 did not produce a significant alteration in the estimate for this outcome (MD −4.96, 95% CI −7.47 to −2.46; I² = 98%; 18 studies, 1484 participants).

Adverse events

The exclusion of Dunzendorfer 1983 did not produce a significant alteration to the estimate for this outcome (RR 1.44, 95% CI 1.05 to 1.99; I² = 33%; 17 studies, 1548 participants).

Subgroup analysis: co‐interventions

Prostatitis symptoms

a) Studies that did not add any co‐interventions to the alpha blocker versus placebo comparison: MD −3.56, 95% CI −5.26 to −1.86; I² = 67%; 7 studies, 688 participants.

b) Studies that added co‐interventions (analgesics or antibiotics, or both) to the alpha blocker versus placebo comparison: MD −5.69, 95% CI −8.90 to −2.48; I² = 99%; 11 studies, 836 participants.

Test for subgroup differences: Chi² = 1.33, df = 1 (P = 0.25), I² = 24.7% (Analysis 1.16).

1.16 — Comparison 1 Alpha‐blockers versus placebo, Outcome 16 Prostatitis symptoms: short term (subgroup analysis by co‐interventions).

Adverse events

a) Studies that did not include any co‐interventions to the alpha blocker versus placebo comparison: RR 1.69, 95% CI 1.10 to 2.60; I² = 59%; 11 studies, 1089 participants.

b) Studies that included co‐interventions (analgesics or antibiotics, or both) to the alpha blocker versus placebo comparison: RR 1.20, 95% CI 0.46 to 3.17; I² = 0%; 8 studies, 499 participants.

Test for subgroup differences: Chi² = 0.39, df = 1 (P = 0.53), I² = 0% (Analysis 1.17).

1.17 — Comparison 1 Alpha‐blockers versus placebo, Outcome 17 Adverse events (subgroup analysis by co‐interventions).

No other predefined sensitivity analysis was possible for this comparison.

Studies not included in meta‐analysis or 'Summary of findings' table

Three studies were not included in meta‐analysis due to missing outcome data:

Cha 2009, with 103 participants, compared levofloxacin, levofloxacin plus alfuzosin, and a levofloxazin plus terpene mixture. Participants who received levofloxacin plus alfuzosin had fewer prostatitis symptoms measured by NIH‐CPSI scores (mean score 13) compared to those who received levofloxacin alone (mean score 15.4) at eight‐week follow‐up. Two participants in the alfuzosin group suffered from dizziness. P values and standard deviations were not available. No other outcomes relevant for this review were reported in this study.
Gül 2001, with 91 participants, compared terazosin and placebo. Participants who received terazosin had fewer prostatitis symptoms measured by PSSI scores (0 to 12 score, benefit is indicated by lower scores: MD −2.56, 95% CI −3.64 to −1.48). The study reported that none of the participants suffered adverse events. No other outcomes relevant for this review were reported in this study.
Lacquaniti 1999, with 80 participants, compared terazosin, tamsulosin and placebo. Participants who received terazosin and tamsulosin had fewer prostatitis symptoms measured by PSSI scores (0 to 12 score, benefit is indicated by lower scores: mean score in the terazosin group 1.221 and mean score in the tamsulosin group 1.324) compared to the placebo group (mean score 4.211, P < 0.05). Five participants in the terazosin group suffered from hypotension, six participants in the tamsulosin group suffered from retrograde ejaculation, and two participants in the placebo group suffered from epigastric pain and hypotension. No other outcomes relevant for this review were reported in this study.

2. 5‐alpha reductase inhibitors versus placebo

Two studies with 177 randomized participants (Leskinen 1999; Nickel 2004a) compared the use of a 5‐alpha reductase inhibitor (finasteride) versus placebo. See Table 9 and Table 10 for further details of the participants and interventions. See Table 2. One additional study was not included in this summary due to missing data and is described below (Leskinen 1999). We found only short‐term outcomes under this comparison.

2.1 Prostatitis symptoms

Based on one study with 64 participants with six‐month follow‐up (Nickel 2004a), finasteride probably causes a small reduction in prostatitis symptoms compared to placebo (MD −4.60, 95% CI −5.43 to −3.77; Analysis 2.1). The quality of evidence was moderate, due to unclear or high risk of bias in most domains. This drug may have resulted in little to no difference in the responders rate compared to placebo or to no additional treatment, but we are very uncertain about these results (RR 2.13, 95% CI 0.82 to 5.53; I² = 0%; Analysis 2.2). The quality of evidence was low, due to unclear or high risk of bias in most domains and imprecision (the confidence interval includes appreciable benefits and harms).

2.1 — Comparison 2 5 alpha reductase inhibitors versus placebo, Outcome 1 Prostatitis symptoms.

2.2 — Comparison 2 5 alpha reductase inhibitors versus placebo, Outcome 2 Prostatitis symptoms: responder rate.

2.2. Adverse events

Based on the two included studies under this comparison, finasteride may make little to no difference in the incidence of adverse events (RR 0.87, 95% CI 0.33 to 2.30; I² = 0%; 2 studies, 105 participants; Analysis 2.3). Common adverse events included: decrease libido, fatigue, mood change and gastrointestinal discomfort. The quality of evidence is low, due to unclear or high risk of bias in most domains in most studies, and imprecision (the confidence interval includes appreciable benefits and harms).

2.3 — Comparison 2 5 alpha reductase inhibitors versus placebo, Outcome 3 Adverse events.

2.3. Sexual dysfunction

None of the included studies reported this outcome.

2.4. Quality of life

None of the included studies reported this outcome.

2.5. Anxiety and depression

None of the included studies reported this outcome.

2.6. Urinary symptoms

None of the included studies reported this outcome (see below).

Study not included in meta‐analysis or 'Summary of findings' table

One study was not included in meta‐analysis due to missing outcome data: a study with 41 participants (Leskinen 1999) compared the use of finasteride to placebo. The authors reported that those participants who received finasteride had fewer prostatitis symptoms at 12‐month follow‐up measured by NIH‐CPSI scores (mean decrease in scores estimated from a graph in the finasteride group was 16 points, and 8 points in the placebo group, P value not available). Participants in the finasteride group had a similar decrease in urinary symptoms to those in the placebo group at 12‐month follow‐up, measured by IPSS scores (mean decrease in both groups estimated from graphs was 8 points).

3. Antibiotics versus placebo

Six studies with 693 randomized participants compared the use of antibiotics versus placebo (Alexander 2004; Kim 2011a; Kulovac 2007; Nickel 2003a; Wang 2016; Ye 2008). All studies used quinolones (levofloxacin and ciprofloxacin). See Table 9 and Table 10 for further details of the participants and interventions. See Table 3. Three studies were not included in this summary, due to missing data, and are described below (Cheng 2010; Choe 2014; Zhou 2008). We found only short‐term outcomes under this comparison.

3.1. Prostatitis symptoms

Five studies with 372 participants fully reported this outcome as total NIH‐CPSI scores at six‐week to three‐month follow‐up (Alexander 2004; Kim 2011a; Kulovac 2007; Nickel 2003a; Wang 2016), and one study (Ye 2008) with 105 participants only reported subscores. Antibiotics may result in a small reduction in prostatitis symptoms (random‐effects meta‐analysis, MD −2.43, 95% CI −4.72 to −0.15; I² = 75%; Analysis 3.1). This effect was evident in the pain subscore (Analysis 3.2) but not in the urinary symptoms or the quality of life subscores (Analysis 3.3; Analysis 3.4). The quality of evidence was low, due to high risk of bias (unclear or high risk of bias in most domains in the main study of this comparison) and inconsistency (statistical heterogeneity).

3.1 — Comparison 3 Antibiotic therapy versus placebo, Outcome 1 Prostatitis symptoms.

3.2 — Comparison 3 Antibiotic therapy versus placebo, Outcome 2 Prostatitis symptoms: pain.

3.3 — Comparison 3 Antibiotic therapy versus placebo, Outcome 3 Prostatitis symptoms: urinary.

3.4 — Comparison 3 Antibiotic therapy versus placebo, Outcome 4 Prostatitis symptoms: quality of life.

Based on two studies with 178 participants with six‐month follow‐up (Alexander 2004; Nickel 2003a), antibiotics may have resulted in little to no difference in responder rate compared to placebo (random‐effects meta‐analysis, RR 1.12, 95% CI 0.73 to 1.74; I² = 0%; Analysis 3.5). The quality of evidence was low, due to unclear or high risk of bias in most domains in the main study of this comparison, and imprecision (few events, resulting in a confidence interval that includes appreciable benefits and harms).

3.5 — Comparison 3 Antibiotic therapy versus placebo, Outcome 5 Prostatitis symptoms: responder rate.

3.2. Adverse events

Based on four studies with 336 participants (Alexander 2004; Nickel 2003a; Wang 2016; Ye 2008), antibiotics probably result in little to no difference in adverse events (RR 1.01, 95% CI 0.66 to 1.55; I² = 0%; Analysis 3.6). Common adverse events included: dyspepsia, diarrhoea, sleep disorders, joint and articular pain, and upper respiratory complaints. The quality of evidence was moderate, due to imprecision (the confidence interval crosses the threshold for the MCID).

3.6 — Comparison 3 Antibiotic therapy versus placebo, Outcome 6 Adverse events.

3.3. Sexual dysfunction

Based on one study with 77 participants (Wang 2016), antibiotics probably result in little to no effect on sexual dysfunction at six‐week follow‐up (MD in IIEF scale 0.40, 95% CI −1.59 to 2.39; Analysis 3.7). The quality of evidence was moderate, due to high or unclear risk of bias in most domains.

3.7 — Comparison 3 Antibiotic therapy versus placebo, Outcome 7 Sexual dysfunction.

3.4. Quality of life

Based on one study with 87 participants (Alexander 2004), antibiotics probably result in little to no effect on quality of life at six‐week follow‐up (MD in SF‐12 scale −3.90, 95% CI −7.94 to 0.14 (Analysis 3.8) for the mental domain, and MD 1.00, 95% CI −2.07 to 4.07 for the physical domain; Analysis 3.9). The quality of evidence was moderate, due to imprecision (the confidence interval crosses the threshold for the MCID).

3.8 — Comparison 3 Antibiotic therapy versus placebo, Outcome 8 Quality of life: mental.

3.9 — Comparison 3 Antibiotic therapy versus placebo, Outcome 9 Quality of life: physical.

3.5. Anxiety and depression

None of the included studies reported this outcome.

3.6. Urinary symptoms

Based on one study with 68 participants (Kim 2011a), antibiotics probably result in little to no effect in urinary symptoms at three‐month follow‐up (MD −1.10, 95% CI −2.88 to 0.68; Analysis 3.10). The quality of evidence was moderate, due to high or unclear risk of bias in most domains.

3.10 — Comparison 3 Antibiotic therapy versus placebo, Outcome 10 Urinary symptoms.

Sensitivity analysis: risk of bias

Prostatitis symptoms

Excluding all studies with unclear or high risk of bias, we included only one study with 196 participants under this comparison (Alexander 2004). This study indicated that there was a small reduction in prostatitis symptoms in those participants who received antibiotics compared to placebo (NIH‐CPSI scores, MD −2.80, 95% CI −5.45 to −0.15). When analysing the number of responders, antibiotics made little to no difference in the responder rate (RR 1.00, 95% CI 0.48 to 2.09).

Adverse events

Excluding all studies with unclear or high risk of bias, we included only one study with 196 participants under this comparison (Alexander 2004). This study indicated that antibiotics made little to no difference in the incidence of adverse events (RR 0.97, 95% CI 0.60 to 1.57).

No other predefined sensitivity analysis was possible for this comparison.

Subgroup analysis: age > 50 years versus age < 50 years

Prostatitis symptoms

a) Studies that included participants with a mean age above 50 years: one study (Nickel 2003a) MD 0.60, 95% CI −3.79 to 4.99; 1 study, 80 participants.

b) Studies that included participants with a mean age less than 50 years: four studies (Alexander 2004; Kim 2011a; Kulovac 2007; Wang 2016) MD −2.92, 95% CI −5.37 to −0.46; I² = 78%; 4 studies, 292 participants.

The test for subgroup differences was not significant: Chi² = 1.88, df = 1 (P = 0.17), I² = 46.8% (Analysis 3.11).

3.11 — Comparison 3 Antibiotic therapy versus placebo, Outcome 11 Prostatitis symptoms: subgroup analysis (age).

Adverse events

a) Studies that included participants with a mean age above 50 years: one study (Nickel 2003a) RR 1.17, 95% CI 0.46 to 2.97; 1 study, 80 participants.

b) Studies that included participants with a mean age less than 50 years: three studies (Alexander 2004; Ye 2006; Wang 2016) RR 0.97, 95% CI 0.60 to 1.57; I² = 0%; 3 studies, 256 participants.

The test for subgroup differences was not significant: Chi² = 0.12, df = 1 (P = 0.73), I² = 0% (Analysis 3.12).

3.12 — Comparison 3 Antibiotic therapy versus placebo, Outcome 12 Adverse events: subgroup analysis (age).

Subgroup analysis: co‐interventions

Prostatitis symptoms

a) Studies that did not add any co‐interventions to the antibiotic versus placebo comparison: MD −1.57, 95% CI −4.77 to 1.63; I² = 41%; 2 studies, 167 participants.

b) Studies that added co‐interventions (alpha blockers) with the antibiotics versus placebo comparison: MD −2.96, 95% CI −6.28 to 0.37; I² = 85%; 3 studies, 205 participants.

Test for subgroup differences: Chi² = 0.35, df = 1 (P = 0.56), I² = 0% (Analysis 3.13).

3.13 — Comparison 3 Antibiotic therapy versus placebo, Outcome 13 Prostatitis symptoms: subgroup analysis (co‐interventions).

Adverse events

a) Studies that did not add any co‐interventions to the antibiotics versus placebo comparison: RR 1.01, 95% CI 0.66 to 1.55; I² = 0%; 2 studies, 175 participants.

b) Studies that added co‐interventions (alpha blockers) to the antibiotics versus placebo comparison: not estimable (no adverse events in the included studies).

Test for subgroup differences: Not applicable (Analysis 3.14).

3.14 — Comparison 3 Antibiotic therapy versus placebo, Outcome 14 Adverse events: subgroup analysis (co‐interventions).

No other predefined subgroup analysis was possible for this comparison.

Studies not included in meta‐analysis or 'Summary of findings' table

Three studies were not included in meta‐analysis due to missing outcome data:

Cheng 2010, with 215 participants, compared levofloxacin 500 mg, ciprofloxacin 500 mg, levofloxacin 1 g and no antibiotics. Participants who received levofloxacin had fewer prostatitis symptoms compared to those who received ciprofloxacin or no antibiotics (P < 0.05; study available as abstract only) at six‐week follow‐up. No other outcomes relevant for this review were reported in this study.
Choe 2014, with 75 participants, compared roxithromycin, ciprofloxacin and aceclofenac. Prostatitis symptoms: participants had a mean NIH‐CPSI score at 12‐week follow‐up of 9.8 in the roxithromycin group, 10 in the ciprofloxacin group and 14.3 in the aceclofenac group, but the authors reported that analysis of variance (ANOVA) yielded P values > 0.05. This study also reported the number of responders (six‐point decrease of NIH‐CPSI scores) at 12‐week follow‐up: 15/25 in the roxithromycin group, 13/25 in the ciprofloxacin group and 18/25 in the aceclofenac group (Chi² and P > 0.05). At 12‐week follow‐up, the three groups had similar urinary symptoms measured by IPSS scores (ANOVA P > 0.05). "Three cases of mild dyspepsia, one case of diarrhoea, and one case of mild skin rash were reported", but the authors did not specify which treatment the participants had received. No other outcomes relevant for this review were reported in this study.
Zhou 2008, with 48 participants, compared tetracycline and placebo. The focus of this study was microbiological results. The study reported that participants who received tetracycline at three‐month follow‐up had a decrease in prostatitis measured by NIH‐CPSI scores (from 35.6 to 17.1), and "in the control group, however, no significant change was found in the [NIH]‐CPSI scores after placebo treatment". No other information was provided for the comparison between groups (mean differences, P values). No other outcomes relevant for this review were reported in this study.

4. Anti‐inflammatories versus placebo

Nine studies with 763 randomized participants were included under this comparison using different anti‐inflammatory agents: corticosteroids (Bates 2007; Yang 2009), antileukotrienes (Goldmeier 2005), nonsteroidal antiinflammatory drugs (NSAID) (Jiang 2009; Kim 2003; Kim 2011a; Wu 2008; Zhao 2009), and tiocolchicoside (Tuğcu 2007). See Table 9 and Table 10 for further details of the participants and interventions. See Table 4. Three additional studies were not included in this summary due to missing data, and are described below (Nickel 2003b; Tugcu 2006; Zeng 2004).

4.1. Prostatitis symptoms

Based on seven studies with 585 participants (Jiang 2009; Kim 2003; Kim 2011a; Tuğcu 2007; Wu 2008; Yang 2009; Zhao 2009), anti‐inflammatories may cause a small reduction in prostatitis symptoms when compared to placebo at six‐week to six‐month follow‐up (random‐effects meta‐analysis, MD −2.50, 95% CI −3.74 to −1.26; I² = 88%; Analysis 4.1). This effect was only evident in the analysis of subscores of pain, but not in urinary symptoms and quality of life (Analysis 4.2; Analysis 4.3; Analysis 4.4). The quality of the evidence is low, due to high or unclear risk of bias in most studies, and inconsistency (high statistical heterogeneity).

4.1 — Comparison 4 Antiinflammatories versus placebo, Outcome 1 Prostatitis symptoms.

4.2 — Comparison 4 Antiinflammatories versus placebo, Outcome 2 Prostatitis symptoms: pain.

4.3 — Comparison 4 Antiinflammatories versus placebo, Outcome 3 Prostatitis symptoms: urinary.

4.4 — Comparison 4 Antiinflammatories versus placebo, Outcome 4 Prostatitis symptoms: quality of life.

Based on two studies with 82 participants (Bates 2007; Zhao 2009), anti‐inflammatories may have resulted in little to no difference in responder rate compared to placebo (random‐effects meta‐analysis, RR 1.44, 95% CI 0.68 to 3.03; I² = 0%; Analysis 4.5). The quality of the evidence is low, due to high or unclear risk of bias in most studies, and imprecision (few events, resulting in a confidence interval that includes appreciable benefits and harms).

4.5 — Comparison 4 Antiinflammatories versus placebo, Outcome 5 Prostatitis symptoms: responder rate.

Tuğcu 2007, with 90 participants, reported long‐term results. For the comparison of tiocolchicoside, ibuprofen and terazosin versus terazosin alone, participants in the combined therapy group probably have fewer prostatitis symptoms (MD −10.50, 95% CI −11.12 to −9.88; Analysis 4.6). The quality of the evidence is moderate, due to high risk of bias.

4.6 — Comparison 4 Antiinflammatories versus placebo, Outcome 6 Prostatitis symptoms: long term.

4.2. Adverse events

Based on seven studies with 540 participants with four‐week to six‐month follow‐up (Goldmeier 2005; Jiang 2009; Kim 2003; Tuğcu 2007; Wu 2008; Yang 2009; Zhao 2009), anti‐inflammatories may result in little to no difference in adverse events (random‐effects meta‐analysis, RR 1.27, 95% CI 0.81 to 2.00; I² = 9%; Analysis 4.7). The quality of the evidence is low, due to high or unclear risk of bias in most studies, and imprecision (few events, resulting in a confidence interval that includes appreciable benefits and harms). Common adverse events included: nausea and gastrointestinal discomfort, heartburn, skin rash and hypersensitivity.

4.7 — Comparison 4 Antiinflammatories versus placebo, Outcome 7 Adverse events.

4.3. Sexual dysfunction

None of the included studies reported this outcome.

4.4. Quality of life

None of the included studies reported this outcome.

4.5. Anxiety and depression

None of the included studies reported this outcome.

4.6. Urinary symptoms

Based on one study with 72 participants (Kim 2011a) with three‐month follow‐up, anti‐inflammatories probably result in little to no difference in urinary symptoms (MD −1.30, 95% CI −2.97 to 0.37; Analysis 4.8). The quality of evidence is moderate, due to high risk of bias.

4.8 — Comparison 4 Antiinflammatories versus placebo, Outcome 8 Urinary symptoms.

Subgroup analysis: co‐interventions

Prostatitis symptoms

a) Studies that did not add any co‐interventions to the anti‐inflammatories versus placebo comparison: MD −3.62, 95% CI −4.85 to −2.39; 1 study, 64 participants.

b) Studies that added co‐interventions (alpha blockers or antibiotics) to the anti‐inflammatories versus placebo comparison: MD −2.29, 95% CI −3.67 to −0.90; I² = 89%; 6 studies, 521 participants.

Test for subgroup differences: Chi² = 1.99, df = 1 (P = 0.16), I² = 49.8%; (Analysis 4.9).

4.9 — Comparison 4 Antiinflammatories versus placebo, Outcome 9 Prostatitis symptoms: subgroup analysis (co‐interventions).

Adverse events

a) Studies that did not add any co‐interventions to the anti‐inflammatories versus placebo comparison: RR 2.00, 95% CI 0.19 to 20.97; 1 study, 64 participants.

b) Studies that added co‐interventions (alpha blockers or antibiotics) to the anti‐inflammatories versus placebo comparison: RR 1.25, 95% CI 0.73 to 2.15; ; I² = 25%; 6 studies, 476 participants.

Test for subgroup differences: Chi² = 0.14, df = 1 (P = 0.70), I² = 0%; (Analysis 4.10).

4.10 — Comparison 4 Antiinflammatories versus placebo, Outcome 10 Adverse events.

No other predefined subgroup analysis was possible for this comparison.

Studies not included in meta‐analysis or 'Summary of findings' table

Three studies were not included in meta‐analysis due to missing outcome data:

Nickel 2003b, with 161 participants, compared rofecoxib in 50 mg and 25 mg doses to placebo. At six‐week follow‐up, participants had a similar decrease in prostatitis symptoms: mean change from baseline NIH‐CPSI was −4.2 in the placebo group, −4.9 in the rofecoxib 25 mg (P = 0.68 compared to placebo) and −6.2 in the rofecoxib 50 mg group (P = 0.68 compared to placebo). There was a greater number of responders (defined as a six‐point decrease in NIH‐CPSI scores) at six‐week follow‐up in the rofecoxib 50 mg group (62.5%) compared to the placebo group (39.7%; P = 0.031); however, there were no differences between the rofecoxib 25 mg group (46.2%) and the placebo group. Adverse events: two participants in the placebo group suffered from chest pain and atrial flutter, and two in the rofecoxib 50 mg group suffered from chest pain. No other outcomes relevant for this review were reported in this study. Note: this drug was withdrawn from the market in 2004 due to a increased risk of heart attack (Sibbald 2004).
Zeng 2004, with 60 participants, compared celecoxib 200 mg once daily or twice daily. At six‐week follow‐up, participants in the celecoxib twice‐daily group had fewer prostatitis symptoms compared to those in the celecoxib once‐daily group (MD −5.20, 95% CI −5.88 to −4.52). One participant in the celecoxib twice‐daily group suffered from headache and one participant in the celecoxib once‐daily group suffered from mild diarrhoea. No other outcomes relevant for this review were reported in this study.
Tugcu 2006, with 45 participants, compared the use of tiocolchicoside, ibuprofen and terazosin versus terazosin alone. Participants in both groups had similar prostatitis symptoms at six‐ and 12‐month follow‐up (only subscores were available, P > 0.05). No other outcomes relevant for this review were reported in this study.

5. Phytotherapy versus placebo

Seven studies with 551 randomized participants were included under this comparison, using different phytotherapeutic agents: Prolit super septo® (combined agents) (Breusov 2014); calendula‐curcuma (Morgia 2017); cranberry (Park 2005); quercetin (Shoskes 1999); pollen extract (Elist 2006; Wagenlehner 2009; Ye 2006). See Table 9 and Table 10 for further details of the participants and interventions. See Table 5. Fourteen studies were not included in this meta‐analysis due to missing data or because they do not compare phytotherapy to placebo (head‐to‐head comparisons) and are described below (Apolikhin 2010; Cai 2014; Cai 2017; Cha 2009; Giammusso 2017; Iwamura 2015; Kaplan 2004; Lee 2006a; Macchione 2017; Maurizi 2019; Morgia 2010; Okada 1985; Reissigl 2004; Xu 2000). One study assessing the effects of cytoflavin did not report outcomes relevant to this review (Churakov 2012).

5.1. Prostatitis symptoms

Based on five studies with 320 participants with one‐ to three‐month follow‐up (Breusov 2014; Morgia 2017; Park 2005; Shoskes 1999; Wagenlehner 2009), phytotherapy may reduce prostatitis symptoms compared to placebo (random‐effects meta‐analysis, MD −5.02, 95% CI −6.81 to −3.23; I² = 60%; Analysis 5.1). These lower scores were observed across all subscores of pain, urinary symptoms and QoL (Analysis 5.2; Analysis 5.3; Analysis 5.4). The quality of evidence was low, due to unclear or high risk of bias in most domains in most studies, and imprecision (the confidence interval crosses the threshold for the MICD).

5.1 — Comparison 5 Phytotherapy versus placebo, Outcome 1 Prostatitis symptoms.

5.2 — Comparison 5 Phytotherapy versus placebo, Outcome 2 Prostatitis symptoms: pain subscore.

5.3 — Comparison 5 Phytotherapy versus placebo, Outcome 3 Prostatitis symptoms: urinary symptoms.

5.4 — Comparison 5 Phytotherapy versus placebo, Outcome 4 Prostatitis symptoms: quality of life.

Based on three studies with 224 participants with one‐ to three‐month follow‐up (Breusov 2014; Shoskes 1999; Wagenlehner 2009), phytotherapy probably increases the responder rate compared to placebo (random‐effects meta‐analysis, RR 1.78, 95% CI 1.25 to 2.52; I² = 27%; Analysis 5.5). The quality of evidence was moderate, due to unclear or high risk of bias in most domains in the main study of this comparison.

5.5 — Comparison 5 Phytotherapy versus placebo, Outcome 5 Prostatitis symptoms: responder rate.

5.2. Adverse events

Based on seven studies with 540 participants with one‐ to three‐month follow‐up (Breusov 2014; Elist 2006; Morgia 2017; Park 2005; Shoskes 1999; Wagenlehner 2009; Ye 2006), phytotherapy may result in little to no difference in adverse events (random‐effects meta‐analysis, RR 1.13, 95% CI 0.54 to 2.36; I² = 0%; Analysis 5.6). The quality of the evidence is low, due to high or unclear risk of bias in most studies, and imprecision (few events, resulting in a confidence interval that includes appreciable benefits and harms). Common adverse events included: gastrointestinal discomfort including nausea, dyspepsia and diarrhoea, headache, and skin rash.

5.6 — Comparison 5 Phytotherapy versus placebo, Outcome 6 Adverse events.

5.3. Sexual dysfunction

Based on one study with 48 participants (Morgia 2017), phytotherapy (in this case, calendula‐curcuma) may have improved sexual dysfunction at three‐month follow‐up (MD in IIEF score 3.50, 95% CI 2.67 to 4.33; Analysis 5.7). The quality of the evidence was low, due to high risk of bias and imprecision (the confidence interval crosses the threshold for the MCID).

5.7 — Comparison 5 Phytotherapy versus placebo, Outcome 7 Sexual dysfunction.

5.4. Quality of life

None of the included studies reported this outcome.

5.5. Anxiety and depression

None of the included studies reported this outcome.

5.6. Urinary symptoms

Based on one study with 139 participants (Wagenlehner 2009), phytotherapy (in this case pollen extract) probably resulted in little to no difference in urinary symptoms at 12‐week follow‐up (IPSS score MD −1.14, 95% CI −2.36 to 0.08; Analysis 5.8). The quality of evidence was moderate, due to high risk of bias.

5.8 — Comparison 5 Phytotherapy versus placebo, Outcome 8 Urinary symptoms.

Sensitivity analysis: diagnostic criteria

We performed a sensitivity analysis excluding Shoskes 1999, which did not meet the Research Consensus definition for CP/CPPS (Nickel 1999).

Prostatitis symptoms

The exclusion of Shoskes 1999 did not produce a significant alteration to the estimate for this outcome (MD −4.95, 95% CI −6.99 to −2.91; I² = 70%; 4 studies, 292 participants).

Adverse events

The exclusion of Shoskes 1999 did not produce a significant alteration to the estimate for this outcome (RR 1.07, 95% CI 0.49 to 2.34; I² = 0%; 6 studies, 512 participants = 512).

No other predefined sensitivity analysis was possible for this comparison.

Subgroup analysis: co‐interventions

Prostatitis symptoms

a) Studies that did not add any co‐interventions to the phytotherapy versus placebo comparison: MD −6.06, 95% CI −7.28 to −4.84; I² = 0%; 3 studies, 133 participants.

b) Studies that added co‐interventions (alpha blockers or antibiotics, or both) to the phytotherapy versus placebo comparison: MD −3.92, 95% CI −6.76 to −1.08; I² = 75%; 2 studies, 187 participants.

Test for subgroup differences: Chi² = 1.84, df = 1 (P = 0.17), I² = 45.7% (Analysis 5.9).

5.9 — Comparison 5 Phytotherapy versus placebo, Outcome 9 Prostatitis symptoms: subgroup analysis (co‐interventions).

Adverse events

a) Studies that did not add any co‐interventions to the phytotherapy versus placebo comparison: RR 2.09, 95% CI 0.33 to 13.30; I² = 0%; 4 studies, 191 participants.

b) Studies that added co‐interventions (alpha blockers or antibiotics, or both) to the phytotherapy versus placebo comparison: RR 1.14, 95% CI 0.34 to 3.79; I² = 17%; 3 studies, 349 participants.

Test for subgroup differences: Chi² = 0.29, df = 1 (P = 0.59), I² = 0% (Analysis 5.10).

5.10 — Comparison 5 Phytotherapy versus placebo, Outcome 10 Adverse events: subgroup analysis (co‐interventions).

No other predefined sensitivity analysis was possible for this comparison.

Studies not included in meta‐analysis or 'Summary of findings' table

Fourteen studies were not included in this summary due to missing data or because they do not compare phytotherapy to placebo (head‐to‐head comparisons) and are described below.

Pollen extract

Apolikhin 2010, with 78 participants, compared the use of a pollen extract pill (Cernilton®) three times a day for three months at a single dose or a double dose (two pills in each dose). Participants who received a higher dose may have had fewer prostatitis symptoms at six‐month follow‐up compared to those with a single dose (MD in NIH‐CPSI scores −2.40, 95% CI −4.28 to −0.52). No other outcomes relevant to this review were reported in this study.
Cai 2014, with 87 participants, compared the use of a pollen extract pill (Deprox®) and ibuprofen. Participants who received pollen extract had fewer prostatitis symptoms than those who received ibuprofen at 30‐day follow‐up (MD in NIH‐CPSI scores −6.70, 95% CI −7.65 to −5.75). Participants who received pollen extract and ibuprofen had similar urinary symptoms (MD in IPSS score MD −0.40, 95% CI −1.42 to 0.62). Participants in the pollen extract group had higher quality‐of‐life measurements compared to the ibuprofen group (Quality of Well‑Being scale, range 0 to 1, MD 0.10, 95% CI 0.03 to 0.17). One participant in the pollen extract group suffered from nausea and seven participants in the ibuprofen group suffered from nausea and epigastric pain. No other outcomes relevant to this review were reported in this study.
Cai 2017, with 70 participants, compared the use of a pollen extract pill (Deprox®) and bromelain. Participants who received pollen extract had fewer prostatitis symptoms than those who received bromelain at three‐month follow‐up (MD in NIH‐CPSI scores −10.80, 95% CI −12.51 to −9.09). Participants in the pollen extract group had higher quality‐of‐life measurements compared to the bromelain group (SF‐36 scale MD 3.70, 95% CI 2.45 to 4.95). One participant in the pollen extract group and two participants in the bromelain group suffered from nausea. No other outcomes relevant to this review were reported in this study.
Iwamura 2015, with 100 participants, compared the use of a pollen extract pill and Eviprostat® (a herbal supplement). At eight‐week follow‐up, prostatitis symptoms were similar in both groups (P = 0.76), with a similar incidence of responders (25% decrease in NIH‐CPSI scores: RR 0.80, 95% CI 0.71 to 1.08). There were two non‐severe adverse events in the pollen extract group and one in the Eviprostat® group. No other outcomes relevant to this review were reported in this study. This study included participants with a mean age above 50 years, and it was therefore not possible to conduct subgroup analysis, since no other study was included under this comparison.
Macchione 2017, with 63 participants, compared the use of pollen extract pill (Deprox®) and Serenoa repens. At six‐week follow‐up participants in the pollen extract group had fewer prostatitis symptoms measured by NIH‐CPSI scores compared to the Serenoa repens group (MD −3.70, 95% CI −5.67 to −1.73). Participants in the pollen extract group had fewer urinary symptoms measured by IPSS scores compared to the Serenoa repens group (MD −4.90, 95% CI −7.12 to −2.68). No other outcomes relevant to this review were reported in this study.
Maurizi 2019, with 54 participants, compared the use of pollen extract pill (Deprox®) and quercetin. At four‐week follow‐up participants in the pollen extract group had fewer prostatitis symptoms measured by NIH‐CPSI scores compared to quercetin ( MD −2.63, 95% CI −3.61 to −1.65). Participants in the pollen extract group had similar urinary symptoms measured by IPSS scores compared to the quercetin group (MD −0.37, 95% CI −1.12 to 0.38). No participant suffered adverse in each group. No other outcomes relevant to this review were reported in this study.
Okada 1985, with 76 participants, compared the use of pollen extract to an amino acid compound ("PPC"), and Xu 2000, with 60 participants, compared the use of pollen extract to a sequence of antibiotics. No outcomes relevant to this review were reported in these studies.

Serenoa repens

Morgia 2010, with 102 participants, compared the use of Serenoa repens with other herbal extracts (Profluss®) and Serenoa repens alone. Participants in the Profluss® group had fewer prostatitis symptoms at 16‐week follow‐up (mean NIH‐CPSI score 13.27) compared to the Serenoa repens group (mean NIH‐CPSI score 20.52, P < 0.001). Participants in the Profluss® group had a greater risk of achieving a response in prostatitis symptoms (> 50% reduction in NIH‐CPSI scores) compared to those in the Serenoa repens group (RR 2.00, 95% CI 1.16 to 3.44). Participants in the Profluss® group had fewer urinary symptoms (mean IPSS score 7.6) compared to the Serenoa repens group (mean IPSS score 170.1, P < 0.001). Four participants in the Profluss® group and three in the Serenoa repens groups suffered gastrointestinal adverse events. One participant in the Profluss® group and one in the Serenoa repens group suffered cephalea as an adverse event. No other outcomes relevant to this review were reported in this study.
Kaplan 2004, with 64 participants, compared the use of Serenoa repens to finasteride. The participants had similar prostatitis symptoms in both groups at three‐month follow‐up (results were available only in graph form). At 12‐month follow‐up, prostatitis symptoms measured by the mean NIH‐CPSI score was 24.6 in the Serenoa repens group and 18.1 in the finasteride group (P < 0.02). At 12‐month follow‐up, urinary symptoms measured by the American Urological Association scale (AUA) were similar in both groups (mean score 10.4 in the Serenoa repens group and 11.9 in the finasteride group). Three participants suffered adverse events in the Serenoa repens group (headache) and two participants suffered adverse events in the finasteride group (decreased libido). No other outcomes relevant to this review were reported in this study.
Reissigl 2004, with 142 participants, compared the use of Serenoa repens to placebo. Participants in the Serenoa repens group had a greater risk of achieving a response in prostatitis symptoms (30% to 50% decrease in NIH‐CPSI scores) compared with the placebo group (RR 3.89, 95% CI 2.33 to 6.48). Participants in the Serenoa repens group had a greater risk of achieving a response in urinary symptoms (50% decrease in IPSS scores) compared to the placebo group (RR 4.33, 95% CI 2.46 to 7.62). No other outcomes relevant to this review were reported in this study.
Giammusso 2017, with 44 participants, compared the administration of palmitoylethanolamide to Serenoa repens extract. The authors reported that those who received palmitoylethanolamide had a reduction in prostatitis symptoms (measured by NIH‐CPSI scores) and urinary scores (measured by IPSS scores), but they did not have an improvement in sexual dysfunction (measured by IIEF scores). These outcomes were reported in a narrative fashion and graphically. None of the participants suffered adverse events. No other outcomes relevant to this review were reported in this study.

Terpene mixture

Lee 2006a, with 50 participants, compared the use of a terpene mixture and ibuprofen. At six‐week follow‐up, participants who received the terpene mixture had similar prostatitis symptoms (mean NIH‐CPSI score 16.8) compared to those in the ibuprofen group (mean NIH‐CPSI score 15.3, P = 0.06). The study reported that three participants in the terpene mixture group suffered from heartburn. No other outcomes relevant to this review were reported in this study.
Cha 2009, with 103 participants, compared levofloxacin, levofloxacin plus alfuzosin and levofloxazin plus terpene mixture. Participants who received levofloxacin plus terpene mixture had fewer prostatitis symptoms measured by NIH‐CPSI scores (mean score 12.4) compared to those who received levofloxacin alone (mean score 15.4) at eight‐week follow‐up. One participant in the terpene mixture group suffered from nausea. P values and standard deviations were not available. No other outcomes relevant to this review were reported in this study.

6. Botulinum toxin A versus placebo

Two studies compared the use of botulinum toxin A (BTA) to a sham procedure: one study with 60 participants (Falahatkar 2015) applied the toxin to the prostate, and another study with 29 participants (Gottsch 2011) applied the toxin to pelvic floor muscles. We report the outcomes of these studies separately due to this clinical heterogeneity in the interventions and participants (Gottsch 2011 included participants aged over 50 years, and Falahatkar 2015 included participants with more severe baseline prostatitis symptoms). See Table 9 and Table 10 for further details of the participants and interventions. See Table 6. One study that explored two different BTA injection protocols (Elshawaf 2009) is not included in the 'Summary of findings' table (see below).

6.1. Prostatitis symptoms

6.1.1. Prostatitis symptoms: subgroup intraprostatic injection, participants < 50 years old with basal NIH‐CPSI scores > 30

Based on one study with 60 participants (Falahatkar 2015), intraprostatic BTA injection may have decreased prostatitis symptoms at six‐month follow‐up (MD −25.80, 95% CI −30.15 to −21.45; Analysis 6.1). These results were consistent across all subscores of pain, urinary symptoms and quality of life (Analysis 6.2; Analysis 6.3; Analysis 6.4). The quality of the evidence is low, due to unclear risk of selection bias and imprecision issues (small sample size resulting in a wide confidence interval).

6.1 — Comparison 6 Botulinum toxin A versus placebo, Outcome 1 Prostatitis symptoms.

6.2 — Comparison 6 Botulinum toxin A versus placebo, Outcome 2 Prostatitis symptoms: pain subscore.

6.3 — Comparison 6 Botulinum toxin A versus placebo, Outcome 3 Prostatitis symptoms: urinary subscore.

6.4 — Comparison 6 Botulinum toxin A versus placebo, Outcome 4 Prostatitis symptoms: quality of life.

6.1.2. Prostatitis symptoms: subgroup pelvic floor muscles injection, participants > 50 years old with basal NIH‐CPSI scores < 30

Based on one study with 29 participants (Gottsch 2011), pelvic floor muscle BTA injection may have caused little to no effect in prostatitis symptoms at one‐month follow‐up (MD −2.60, 95% CI −5.59 to 0.39; Analysis 6.1). These results were consistent across subscores of urinary symptoms and quality of life, however pain scores in the BTA group were lower than the control group (Analysis 6.2; Analysis 6.3; Analysis 6.4). The quality of evidence is low, due to high risks of performance and detection bias, and imprecision issues (small sample size resulting in a wide confidence interval).

6.2. Adverse events

The study on intraprostatic BTA injection (Falahatkar 2015) reported that two participants in the active treatment group suffered from haematuria (RR 5.00, 95% CI 0.25 to 99.95; 60 participants; Analysis 6.5). No participants in the study on pelvic floor muscle BTA injection (Gottsch 2011) suffered adverse events. The quality of the evidence is low, due to unclear or high risks of bias and imprecision (few events).

6.5 — Comparison 6 Botulinum toxin A versus placebo, Outcome 5 Adverse events.

6.3. Sexual dysfunction

None of the included studies reported this outcome.

6.4. Quality of life

None of the included studies reported this outcome.

6.5. Anxiety and depression

None of the included studies reported this outcome.

6.6. Urinary symptoms

The study on intraprostatic BTA injection reported this outcome (Falahatkar 2015). Intraprostatic BTA injection may have decreased urinary symptoms (IPSS scores, MD −9.67, 95% CI −13.97 to −5.37; 60 participants; Analysis 6.6). The quality of the evidence is low, due to unclear risk of selection bias, and imprecision issues (small sample size resulting in a wide confidence interval).

6.6 — Comparison 6 Botulinum toxin A versus placebo, Outcome 6 Urinary symptoms.

Studies not included in meta‐analysis or 'Summary of findings' table

One study was not included in meta‐analysis due to missing outcome data. Elshawaf 2009, with 52 participants, compared botulinum toxin A injection in the external urethral sphincter versus a combined injection in the prostate and external urethral sphincter. At six‐month follow‐up, the group with the combined injection had fewer prostatitis symptoms measured by NIH‐CPSI scores (P < 0.05). None of the participants suffered adverse events. No other outcomes relevant for this review were reported in this study.

7. Allopurinol versus placebo

Two studies with 110 participants were included under this comparison (Persson 1996; Ziaee 2006). See Table 9 and Table 10 for further details of the participants and interventions. See Table 7. One of these studies (Persson 1996) reported the incidence of adverse events (see below), but no outcomes relevant for this review were reported in this study, since the authors used a 12‐point scale that was not validated for this condition.

7.1. Prostatitis symptoms

Based on one study with 56 participants with three‐month follow‐up (Ziaee 2006), allopurinol may cause little to no different in prostatitis symptoms compared to placebo (MD −0.21, 95% CI −4.48 to 4.06; Analysis 7.1). This was also evident in pain and urinary subscores (Analysis 7.2; Analysis 7.3). The quality of evidence was low, due to unclear or high risks of bias in most domains and imprecision (the confidence interval includes appreciable benefits and harms).

7.1 — Comparison 7 Allopurinol versus placebo, Outcome 1 Prostatitis symptoms.

7.2 — Comparison 7 Allopurinol versus placebo, Outcome 2 Prostatitis symptoms: pain subscore.

7.3 — Comparison 7 Allopurinol versus placebo, Outcome 3 Prostatitis symptoms: urinary subscore.

7.2. Adverse events

Based on the included studies with 110 participants, no adverse events were observed at three‐month follow‐up. The quality of the evidence is low, due to high or unclear risks of bias in both studies, and imprecision (zero events).

7.3. Sexual dysfunction

None of the included studies reported this outcome.

7.4. Quality of life

None of the included studies reported this outcome.

7.5. Anxiety and depression

None of the included studies reported this outcome.

7.6. Urinary symptoms

None of the included studies reported this outcome.

8. Traditional Chinese medicine (TCM) versus placebo

Seven studies with 970 randomized participants were included under this comparison (Hu 2015; Li 2003; Li 2012; Sun 2008; Tan 2009; Xia 2014; Zhang 2007). See Table 9 and Table 10 for further details of the participants and interventions. See Table 8. Five studies were not included in the 'Summary of findings' table and are described below (Chen 2009; Li 2007; Peng 2003; Shi 1994; Wang 2004).

8.1. Prostatitis symptoms

Based on seven studies with 835 participants with two‐week to two‐month follow‐up (Hu 2015; Li 2003; Li 2012; Sun 2008; Tan 2009; Xia 2014; Zhang 2007), TCM may reduce prostatitis symptoms compared to placebo (MD ‐3.13, 95% CI ‐4.99 to ‐1.28; I² = 82%, Analysis 8.1). These results were consistent in the pain and urinary subscores but not quality of life subscore (Analysis 8.2; Analysis 8.3; Analysis 8.4). The quality of evidence was low, due to high risk of bias (unclear or high risk of bias in most domains in most studies) and inconsistency (I² > 80%), although some of this inconsistency might be explained by the differences between the interventions in this comparison (possible indirectness).

8.1 — Comparison 8 Traditional chinese medicine versus placebo or usual care, Outcome 1 Prostatitis symptoms.

8.2 — Comparison 8 Traditional chinese medicine versus placebo or usual care, Outcome 2 Prostatitis symptoms: pain subscore.

8.3 — Comparison 8 Traditional chinese medicine versus placebo or usual care, Outcome 3 Prostatitis symptoms: urinary subscore.

8.4 — Comparison 8 Traditional chinese medicine versus placebo or usual care, Outcome 4 Prostatitis symptoms: quality of life.

8.2. Adverse events

Based on four studies with 584 participants at four‐ to eight‐week follow‐up (Li 2003; Li 2012; Tan 2009; Zhang 2007), TCM may cause little to no difference in adverse events compared to placebo (RR 1.34, 95% CI 0.22 to 8.02; I² = 45%; Analysis 8.5). The quality of evidence was low, due to high risk of bias (unclear or high risk of bias in most domains in most studies) and imprecision (few events, resulting in a confidence interval that includes appreciable benefits and harms). Common adverse events included gastrointestinal discomfort, nausea, vomiting and diarrhoea, and anal bleeding (for those TCM interventions that used suppositories).

8.5 — Comparison 8 Traditional chinese medicine versus placebo or usual care, Outcome 5 Adverse events.

8.3. Sexual dysfunction

One study with 88 participants (Xia 2014) reported this outcome at two‐week follow‐up. TCM probably resulted in little to no difference in sexual discomfort when compared to placebo (IIEF scores, MD 0.27, 95% CI −1.17 to 1.71; Analysis 8.6). The quality of evidence is moderate, due to high risk of or unclear risk of bias in most domains of the study.

8.6 — Comparison 8 Traditional chinese medicine versus placebo or usual care, Outcome 6 Sexual dysfunction.

8.4. Quality of life

None of the included studies reported this outcome.

8.5. Anxiety and depression

One study with 88 participants (Xia 2014) reported this outcome at two‐week follow‐up. TCM may have resulted in a decrease in symptoms of anxiety and depression when compared to placebo (Hamilton Anxiety Rating Scale, MD −9.50, 95% CI −11.70 to −7.30; Analysis 8.7; Hamilton Depression Rating Scale, MD −7.84, 95% CI −10.71 to −4.97; Analysis 8.8). The quality of evidence is low, due to high risk of bias (unclear or high risk of bias in most domains in most studies) and imprecision (small sample size resulting in a wide confidence interval that crosses the threshold for the MCID).

8.7 — Comparison 8 Traditional chinese medicine versus placebo or usual care, Outcome 7 Anxiety and depression: anxiety.

8.8 — Comparison 8 Traditional chinese medicine versus placebo or usual care, Outcome 8 Anxiety and depression: depression.

8.6. Urinary symptoms

None of the included studies reported this outcome

Studies not included in meta‐analysis or 'Summary of findings' table

Five studies were not included in meta‐analysis due to missing outcome data or because they involve head‐to‐head comparisons:

Chen 2009, with 70 participants, compared QianTongDing Decoction with indomethacin. Participants who received QianTongDing Decoction may have had fewer prostatitis symptoms at one‐month follow‐up (MD in NIH‐CPSI scores −6.80, 95% CI −7.94 to −5.66). The quality of evidence is low, due to high risk of bias and imprecision issues. Two participants in the indomethacin group suffered from epigastralgia. No participants in the QianTongDing group suffered adverse events. No other outcomes relevant to this review were reported in this study.
Li 2007, with 108 participants, compared a Tiaoshen Tonglin infusion with terazosin. Participants who received Tiaoshen Tonglin infusion may have had fewer prostatitis symptoms at two‐month follow‐up (MD in NIH‐CPSI scores −3.80, 95% CI −4.82 to −2.78). The incidence of adverse events was 2/56 in the Tiaoshen Tonglin and 12/52 in the terazosin group (dizziness and palpitations). The quality of evidence is low, due to high risk of bias and imprecision issues. No other outcomes relevant to this review were reported in this study.
Peng 2003, with 160 participants, compared an "antiphlogistic" agent in different regimens and with various co‐interventions. No outcomes relevant to this review were reported in this study.
Shi 1994, with 60 participants, compared QianLieAnWan capsules and QianLieKang (a type of pollen extract capsule). No outcomes relevant to this review were reported in this study.
Wang 2004, with 38 participants, compared an intraprostatic injection of Chuanshentong to a placebo injection. At six‐week follow‐up there were more participants who had an appreciable reduction in prostatitis symptoms (six or more points decrease in NIH‐CPSI scores) in the active treatment group compared to the placebo group (RR 2.49, 95% CI 1.24 to 4.97). The study stated that there were no adverse events in the active treatment group. No outcomes relevant to this review were reported in this study.

9. Other pharmacological agents

In the following sections we provide a description of the studies that included other pharmacological agents (in alphabetical order). See Table 9 and Table 10 for further details of the participants and interventions.

9.1. Anticholinergics

Three studies with 202 randomized participants were included under this comparison (Kim 2008; Kim 2011b;Lu 2004).

9.1.1. Prostatitis symptoms

Based on the three studies (Kim 2008; Kim 2011b; Lu 2004) with four‐ to eight‐week follow‐up, anticholinergics probably resulted in little to no difference in prostatitis symptoms compared to control (random‐effects meta‐analysis, MD −1.20, 95% CI −3.49 to 1.09; I² = 47%; 3 studies, 173 participants). The quality of evidence was moderate, due to high or unclear risks of bias in most domains.

9.1.2. Adverse events

Two studies with 106 participants reported adverse events (Kim 2008; Lu 2004). These studies reported that there were globally no adverse events. The quality of evidence is low, due to high or unclear risks of bias in most domains, and imprecision (zero events in both groups).

9.1.3. Sexual dysfunction

One study (Kim 2011b) with 96 participants reported sexual dysfunction. Participants who received anticholinergics had similar sexual dysfunction measured by IIEF scores (MD 1.00, 95% CI −1.46 to 3.46). The quality of evidence was moderate, due to high or unclear risks of bias in most domains.

9.1.4. Quality of life

None of the studies reported this outcome.

9.1.5. Depression and anxiety

None of the studies reported this outcome.

9.1.6. Urinary symptoms

Two studies with 133 participants reported urinary symptoms (Kim 2008; Kim 2011b). Participants who received anticholinergics may have a slight reduction in urinary symptoms (MD −2.32, 95% CI −4.24 to −0.40; I² = 0%). The quality of evidence was moderate, due to high or unclear risk of bias in most domains.

9.2. Antidepressants

Five studies with 495 randomized participants evaluated these agents: three studies with 94 participants compared antidepressants to placebo (Giannantoni 2014; Lee 2005; Turkington 2002) and another study with 150 randomized participants compared duloxetine and doxazosin, sertraline and doxazosin, and doxazosin alone (doxazosin acted as a co‐intervention) (Zhang 2017). One additional study with 251 randomized participants compared the use of dapoxetin as add‐on therapy to medical therapy versus medical therapy alone in patients with comorbid premature ejaculation (Zhao 2019) is described separately below.

Antidepressants versus placebo

9.2.1 Prostatitis symptoms

Giannantoni 2014, with 38 participants, reported that those who received duloxetine had fewer prostatitis symptoms compared to those who received placebo (MD −5.97, 95% CI −7.89 to −4.05) at 16‐week follow‐up. Lee 2005, with 14 participants, reported this outcome using the Prostatitis Symptom Severity scale (0 to 100 score, benefit is indicated by lower scores). Participants who received sertraline had statistically non‐significantly lower mean scores (mean score 17.3) compared to those on placebo (mean score 26, P = 0.34) at 13‐week follow‐up. The quality of evidence was very low, due to high risk of bias, inconsistency and imprecision (few events). Zhang 2017, with 150 participants, reported that those in the duloxetine group had fewer prostatitis symptoms at six‐month follow‐up (mean decrease 12.64 points) compared to those receiving sertraline (mean decrease 7.41 points, P < 0.01) and to those receiving doxazosin alone (mean decrease 6.12 points, P < 0.01). The responder rate was greater in the duloxetine group (88.6%) compared to the sertraline group (63.4%) and the doxazosin‐alone group (56.1%).

9.2.2. Adverse events

Based on three studies with 94 participants (Giannantoni 2014; Turkington 2002; Lee 2005) at 8‐ to 16‐week follow‐up, antidepressants may cause little to no difference in adverse events (random‐effects meta‐analysis, RR 1.65, 95% CI 0.54 to 5.04; I² = 14%). The quality of the evidence was low, due to high risk of bias and imprecision (few events). Common adverse events included gastrointestinal discomfort, decreased libido and ejaculatory disorders, sedation and dizziness.

Zhang 2017, with 150 participants, reported narratively: three participants discontinued treatment due to adverse events in the duloxetine group, two in the sertraline group and two in the doxazosin group, and that "[the] occurrence rate of nausea and vomiting was 15.91% in duloxetine group, which was significantly higher than that in the other 2 groups, and some patients were unable to tolerate the adverse reactions".

9.2.3. Sexual dysfunction

Giannantoni 2014, with 38 participants, reported this outcome using the IIEF score. Participants in both groups had similar scores at 16‐week follow‐up: mean score in the duloxetine group was 14.8, mean score in the placebo group was 15.3, P = "NS" (non‐significant). Lee 2005, with 14 participants, reported this outcome using the Psychosexual Questionnaire. Participants in both groups had similar scores at 13‐week follow‐up: mean score in the sertraline group was 22.1, mean score in the placebo group was 23.1, P = 0.44.

The quality of the evidence was low, due to high risk of bias and imprecision (few events).

9.2.4. Quality of life

Turkington 2002, with 42 participants, reported that those who received fluvoxamine had improved quality of life at eight‐week follow‐up (measured by the General Health Questionnaire, mean score in the fluvoxamine group was 5.75 and mean score in the placebo group was 1.25, P < 0.01).

The quality of the evidence was low, due to high risk of bias and imprecision (small sample size, underpowered study).

9.2.5. Depression and anxiety.

Turkington 2002, with 42 participants, reported that both groups had similar symptoms of anxiety and depression at eight‐week follow‐up (measured by Hamilton Depression Scale, P = 0.21 for the anxiety domain and 0.87 for the depression domain).

Giannantoni 2014, with 38 participants, reported that those in the duloxetine group had fewer symptoms of anxiety (mean Hamilton Anxiety scale of 7.93, SD 6.54) compared to those who received placebo (mean score of 15.72, SD 10.11, P < 0.01). The symptoms of depression (measured by Hamilton Depression scale) were fewer in the duloxetine group, but this difference was not statistically significant. Follow‐up was 16 weeks.

Lee 2005, with 14 participants, reported that those who received sertraline had statistically non‐significantly lower mean symptoms of anxiety and depression as measured by the Hospital Anxiety and Depression scale (anxiety score was 6.7, depression score was 3.1 in the sertraline group, while anxiety score was 17.7, and depression score was 5.6 in the placebo group, P value = 0.4 and 0.3 respectively) at 13‐week follow‐up.

Zhang 2017, with 150 participants, reported that those who received duloxetine had fewer symptoms of anxiety and depression at six‐month follow‐up measured by the Hospital Anxiety and Depression Scale (HADS) (mean decrease 9.43 points) compared to those who received sertraline (mean decrease 7.27 points, P < 0.05) and those who received doxazosin alone (mean decrease 4.90 points, P < 0.01).

The quality of evidence was low, due to high risk of bias and imprecision (small sample size, underpowered studies).

9.2.6. Urinary symptoms

None of the included studies reported this outcome.

Antidepressants (dapoxetine) plus medical therapy versus medical therapy alone in men with premature ejaculation

A study with 251 randomized participants compared the use of dapoxetine as add‐on therapy to medical therapy versus medical therapy alone in patients suffering from CP/CPPS with comorbid premature ejaculation (Zhao 2019).

In this study, based on available data from 114 participants, those who received dapoxetine may have had fewer prostatitis symptoms at 12 week follow‐up (NIH‐CPSI score, MD ‐4.37, 95% CI ‐6.88 to ‐1.86) and fewer sexual dysfunction (measured by the Premature Ejaculation Profile with a range from 0 to 16 and higher scores indicating improvement, MD 4.43, 95% CI 2.83 to 6.03) compared to those in the control group. Based on data from 251 participants, the incidence of adverse events was similar in both groups: 7.37% in the dapoxetine group and 4.91% in the control group (RR 1.50, 95% CI 0.45 to 5.04). No outcomes relevant to this review were reported in this study. The quality of the evidence was low due to imprecision and study limitations.

9.3. Mepartricin

Two studies analysed this intervention (Cavallini 2001; De Rose 2004).

Cavallini 2001, with 42 participants, compared mepartricin versus vitamin C (as a placebo comparator). An adverse event was reported in 1/22 participants in the mepartricin group (epigastralgia), with none in the control group. No other outcomes relevant to this review were reported in this study.

De Rose 2004, with 26 participants, compared mepartricin with placebo. At 60‐day follow‐up, participants who received mepartricin had fewer prostatitis symptoms measured by NIH‐CPSI scores (median 10, interquartile range 4 to 25), compared to those who received placebo (median 20, interquartile range 11 to 45, P = 0.0018). Two participants who received mepartricin suffered from epigastralgia. No other outcomes relevant to this review were reported in this study.

The quality of the evidence for the reported outcomes was low, due to high risk of bias and imprecision (small sample size, underpowered studies).

Note: this drug has only limited availability worldwide (some European countries and Brazil).

9.4. OM‐89 (Escherichia coli lysate)

Wagenlehner 2014, with 185 participants, compared the use of OM‐89 versus placebo.

9.4.1. Prostatitis symptoms

OM‐89 probably has little to no effect on prostatitis symptoms (MD −0.60, 95% CI −3.21 to 2.01) compared to those who received placebo at 12‐month follow‐up. The number of participants who achieved a 25% decrease in NIH‐CPSI scores was similar in both groups (RR 0.99, 95% CI 0.78 to 1.25). The quality of the evidence was moderate, due to high risk of bias.

9.4.2. Adverse events

OM‐89 probably has little to no effect on adverse events (RR 0.99, 95% CI 0.78 to 1.25). The quality of the evidence for the reported outcomes was low, due to high risk of bias and imprecision (few events, resulting in a confidence interval that includes appreciable benefits and harms).

9.4.3. Sexual dysfunction, quality of life, anxiety and depression, or urinary symptoms

No other outcomes relevant to this review were reported in this study.

9.5. Pentosan

Two studies with 130 participants (Nickel 2005; Wedren 1987) compared the use of pentosan with placebo.

9.5.1. Prostatitis symptoms

This outcome was reported by Nickel 2005, with 100 participants. Those in the pentosan group probably had similar prostatitis symptoms when compared to the placebo group at 16‐week follow‐up (NIH‐CPSI score MD −2.70, 95% CI −5.61 to 0.21). The quality of evidence is moderate, due to high risk of bias.

9.5.2. Adverse events

In Nickel 2005 adverse events were reported by 36/51 participants receiving pentosan and 34/49 receiving placebo. The most frequent adverse events were diarrhoea, nausea and headache. Six participants in the pentosan group had altered liver function tests, and one of them suffered from liver failure. In Wedren 1987 two participants in the pentosan group suffered from diarrhoea while none in the placebo group reported any adverse event. The quality of evidence is low, due to high risk of bias and imprecision (few events).

9.5.3. Sexual dysfunction, quality of life, anxiety and depression, or urinary symptoms

No other outcomes relevant to this review were reported in the included studies for this comparison.

9.6. Phosphodiesterase inhibitors

We included six studies with 536 randomized participants which compared the addition of phosphodiesterase inhibitors to medical therapy versus medical therapy alone (Abdalla 2018; Kong 2014;Lin 2007;Park 2012; Park 2017; Singh 2017).

9.6.1.Prostatitis symptoms

Based on two studies with 226 participants (Kong 2014; Lin 2007), phosphodiesterase inhibitors may reduce prostatitis symptoms at six‐ to eight‐week follow‐up (random‐effect meta‐analysis, MD −4.37, 95% CI −5.24 to −3.50; I² = 82%). Singh 2017, with 68 participants, reported that the mean decrease in NIH‐CPSI scores at six weeks was 18 in the tadalafil group and 8.4 in the control group (P < 0.05). Park 2012, with 78 participants, reported that the mean decrease in NIH‐CPSI scores at four weeks was 2.7 in the tadalafil group and 1.2 in the control group (P < 0.05). Park 2017, with 86 participants, reported that the mean decrease in NIH‐CPSI scores at four weeks was 7.3 in the tadalafil group and 3.1 in the control group (P < 0.05). Abdalla 2018, with 108 participants, reported that NIH‐CPSI scores were lower at four‐week follow‐up (P < 0.001) in those who received tadalafil and antibiotics compared to those who only received antibiotics. The quality of evidence is low, due to high or unclear risks of bias in most domains, and inconsistency.

9.6.2. Adverse events

Lin 2007, with 138 participants, reported that there were no adverse events. Three studies (Kong 2014; Park 2012; Singh 2017) reported that those in the phosphodiesterase inhibitors group suffered from frequent erections, dyspepsia, back pain, blurred vision and headache (no information on the control group). Abdalla 2018 reported that one participant in the tadalafil group suffered from flushing. The quality of evidence is low, due to high or unclear risks of bias in most domains, and imprecision (few events).

9.6.3. Sexual dysfunction

Two studies with 226 participants provided sufficient information to pool the results in meta‐analysis (Kong 2014; Lin 2007). Participants who received phosphodiesterase inhibitors may have had less sexual dysfunction at six‐ to eight‐week follow‐up (measured by IIEF score, MD 6.80, 95% CI 5.05 to 8.55; I² = 76%). Park 2012, with 78 participants, reported that those in the tadalafil group had less sexual dysfunction at four‐week follow‐up (mean increase in the IIEF score of 3.7) compared to those in the control group (mean increase in the IIEF score of 0.2, P < 0.05). Park 2017, with 86 participants, reported that those in the tadalafil group had less sexual dysfunction at six‐week follow‐up (mean increase in the IIEF score of 3.8) compared to those in the control group (mean increase in the IIEF score of 0.2, P < 0.05). Singh 2017, with 68 participants, reported that those in the tadalafil group had less sexual dysfunction at six‐week follow‐up (mean increase in the IIEF score of 6.4) compared to those in the control group (mean decrease in the IIEF score of −0.7, P < 0.05). Abdalla 2018, with 108 participants, reported less sexual dysfunction (higher IIEF scores) at four‐week follow‐up (P < 0.001) in those who received tadalafil and antibiotics compared to those who received antibiotics alone. The quality of evidence is low, due to high or unclear risks of bias in most domains, and imprecision (mean differences between scores crossed the MCID).

9.6.4. Quality of life

None of the studies reported QoL.

9.6.5. Depression and anxiety

None of the studies reported on depression and anxiety.

9.6.6. Urinary symptoms

Four studies with 320 participants reported this outcome. Kong 2014, with 88 participants, reported that those in the mirodenafil group had a greater decrease in urinary symptoms at six‐week follow‐up (measured by IPSS score, mean decrease of 4.3 points) compared to those in the control group (mean decrease of 1.1 points, P value < 0.05). Park 2012, with 78 participants, reported that those in the tadalafil group had a greater decrease in urinary symptoms at four‐week follow‐up (measured by IPSS score, mean decrease of 2.6 points) compared to those in the control group (mean decrease of 1 point, P value < 0.05). Park 2017, with 86 participants, reported that those in the tadalafil group had a greater decrease in urinary symptoms at six‐week follow‐up (measured by IPSS score, mean decrease of 4.2 points) compared to those in the control group (mean decrease of 1.1 points, P value < 0.05). Singh 2017, with 68 participants, reported that those in the tadalafil group had a greater decrease in urinary symptoms at six‐week follow‐up (measured by IPSS score, mean decrease of 8.8 points) compared to those in the control group (mean decrease of 3.4 points, P value < 0.05). The quality of evidence is low, due to high or unclear risk of bias in most domains, and imprecision (mean differences between scores crossed the MCID).

9.7. Pregabalin

Pontari 2010, with 324 participants, compared the use of pregabalin and placebo.

9.7.1. Prostatitis symptoms

Pregabalin causes little to no difference in prostatitis symptoms compared to placebo at six‐week follow‐up (measured by NIH‐CPSI score, MD −1.90, 95% CI −3.97 to 0.17). The number of participants who achieved a six‐point decrease in the score was similar in both groups (RR 1.32, 95% CI 0.99 to 1.76). The quality of evidence is high.

9.7.2. Adverse events

There were 191 adverse events, and the authors state that there was no difference between groups (P = 0.40), but more participants suffered from neurological symptoms, including headache, in the pregabalin group than in the placebo group (RR 1.70, 95% CI 1.15 to 2.51). The quality of evidence is low, due to imprecision.

9.7.3. Sexual dysfunction

Pregabalin causes little to no difference in sexual dysfunction compared to placebo (measured by the Sexual Health Inventory for Men, MD −0.80, 95% CI −2.69 to 1.09, P = 0.40). The quality of evidence is high.

9.7.4. Quality of life

Pregabalin causes little to no difference in quality of life compared to placebo (measured by the SF‐12 questionnaire; P = 0.34 for physical domain and 0.22 for mental domain). The quality of evidence is high.

9.7.5. Anxiety and depression

Pregabalin causes little to no difference in anxiety and depression compared to placebo (measured by the Hospital Anxiety and Depression Scale, P = 0.36). The quality of evidence is high.

9.7.6. Urinary symptoms

The study did not report this outcome.

9.8. Tanezumab

Nickel 2016, with 62 participants, compared the monoclonal antibody tanezumab with placebo.

9.8.1. Prostatitis symptoms

Participants receiving tanezumab had similar prostatitis symptoms to those who received placebo at six‐week follow‐up (NIH‐CPSI score MD 1.43, 95% CI −6.71 to 3.85). The quality of the evidence is low, due to high risks of bias and imprecision (the confidence interval crosses the threshold for the MCID).

9.8.2. Adverse events

Adverse events were reported in 19/30 participants receiving tanezumab and in 12/32 of those receiving placebo. The most frequent adverse events were paraesthesias, arthralgia, headache, pain in an extremity, and insomnia. The quality of evidence is low, due study limitations and imprecision.

9.8.3. Sexual dysfunction, quality of life, anxiety and depression, or urinary symptoms

No other outcomes relevant to this review were reported in this study.

Discussion

Summary of main results

We included 99 unique studies with 9119 men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), with the assessment of 16 types of pharmacological interventions. Most of our comparisons included short‐term follow‐up information. The median age of the participants was 38 years.

Main comparisons

We found low‐ to very low‐quality evidence that alpha blockers may reduce prostatitis symptoms based on a reduction in NIH‐CPSI scores of more than two (but less than eight) with an increased incidence of minor adverse events such as dizziness and hypotension Moderate‐ to low‐quality evidence indicates that 5‐alpha reductase inhibitors, antibiotics, anti‐inflammatories, and phytotherapy probably cause a small decrease in prostatitis symptoms and may not be associated with a greater incidence of adverse events. Intraprostatic BTA injection may cause a large reduction in prostatitis symptoms with procedure‐related adverse events (haematuria), but pelvic floor muscle BTA injection may not have the same effects (low‐quality evidence). Allopurinol may also be ineffective for the reduction of prostatitis symptoms (low‐quality evidence). We assessed a wide range of interventions involving traditional Chinese medicine; low‐quality evidence showed they may reduce prostatitis symptoms without an increased incidence in adverse events.

Other interventions

Moderate‐ to high‐quality evidence indicates that the following interventions may be ineffective for the reduction of prostatitis symptoms: anticholinergics, OM‐89, pentosan, and pregabalin. Low‐ to very low‐quality evidence indicates that antidepressants and tanezumab may be ineffective for the reduction of prostatitis symptoms. Low‐quality evidences indicates that mepartricin and phosphodiesterase inhibitors may reduce prostatitis symptoms, without an increased incidence in adverse events.

Overall completeness and applicability of evidence

Our review focused on men with CP/CPPS. Almost all the included studies used the consistent inclusion criteria defined by the NIH (Nyberg 1999). These diagnostic criteria are related to clinical practice, since these participants are usually tested for urological diseases that could mimic CP/CPPS. However, some of the impact of the NIH consensus on the diagnosis of CP/CPPS might have changed the classification of participants across time (Krieger 2002), so the results of older trials must be interpreted with caution with the current diagnostic criteria. We incorporated a sensitivity analysis based on this consideration.

We maintained open inclusion criteria for the included interventions. This decision was based on the poorly understood pathophysiological determinants for CP/CPPS (see Background). This led to the inclusion of a wide variety of pharmacological interventions, which could relate to clinical practice, considering that people with CP/CPPS usually try different treatment options before achieving some form of relief. There might be difficulties in the interpretation of some head‐to‐head comparisons, since we do not know the effectiveness of each separate intervention: for example, for the comparison of pollen extract (deprox®) versus bromelain we might not know if pollen extract and bromelain are superior to placebo in the first place in order to analyse their relative effectiveness.

Our review focused on critical patient‐important outcomes; however, most studies did not report them consistently, especially the incidence of adverse events. This is a common problem in clinical trials (Ioannidis 2001), and poses difficulties when estimating the net benefit of the interventions. Additionally, most of the included studies did not report the effects of their interventions on quality of life (QoL), sexual function and mental health, considering the important impact of CP/CPPS in these domains (Krsmanovic 2014). We acknowledge that the NIH‐CPSI score includes QoL and urinary symptom subscores that, alongside the pain subscore, contribute to a total score that has proved to be valid and reliable (Litwin 1999; McNaughton Collins 2001; Propert 2006; Turner 2003); however, these subscores have not been individually validated for these constructs. We acknowledge that the validated scores for QoL, urinary symptoms, sexual dysfunction, and anxiety and depression might not have been validated in the subpopulation of men with CP/CPPS, so their values should be interpreted cautiously, especially using the assessment of the minimal clinically important difference (MCID).

Some pharmacological interventions may have different impacts on the main outcomes for this conditions. For example: phosphodiesterase inhibitors may have a greater impact on sexual dysfunction than on prostatitis symptoms; analgesics alone or in combinations may be used more when pain exacerbations occur. For this purpose, the UPOINTS approach allows the clinician to screen the person's characteristics and needs to guide the selection of pharmacological and non‐pharmacological interventions (Magri 2010; Shoskes 2008b). When considering adverse events, we have listed those most commonly reported in clinical trials. We acknowledge that there might be a wide range of possible adverse events that clinical trials might not have captured, and that observational studies could provide more information on this topic (Singh 2012). Most adverse events were self‐limiting and with minor impact (e.g. gastrointestinal discomfort). In some cases the authors titrated the drugs to reduce the impact of early‐onset adverse events, such as postural hypotension for alpha blockers (Lepor 2007). Additionally, there might be other suggestions, as being cautious when standing up from bed, in order to avoid this adverse event (Figueroa 2010). Other adverse events that may not be transient (e.g. retrograde ejaculation) might be more challenging to treat, and a discussion with the patient may be warranted in order to elicit the importance of these outcomes, especially in relation to sexual activity and expectations (Lepor 2007). Unlike surgery‐induced retrograde ejaculation, this adverse event usually reverts to normal when alpha blockers are suspended.

Furthermore, most studies reported results at four‐ to 12‐week follow‐up, which might be insufficient considering that men with CP/CPPS generally have a long, fluctuating history of symptoms, usually for years (Clemens 2015).

We had planned to explore the effect of the interventions in subgroups of men with different degrees of disease severity and in subgroups of men with common comorbidities (Gasperi 2017), but the included studies provided insufficient data for this, so our analyses were limited.

This review supplements another Cochrane Review in the same area: Non‐pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome (Franco 2018). In that review we highlighted that acupuncture and extracorporeal shockwave therapy are probably beneficial for this condition. While we found no evidence for psychological support for this condition, psychotherapy (e.g. cognitive behavioural therapy) has been effective in the management of somatoform disorders (Van Dessel 2014).

Some of the included treatments for the main comparisons expressed in the 'Summary of findings' tables and in other sections of the review have not been part of routine care for CP/CPPS, especially: anticholinergics, mepartricin, OM‐89, phosphodiesterase inhibitors, pregabalin and tanezumab. In support of this, we used, as an example, the recommendations by the European Association of Urology (available at uroweb.org/guideline/chronic‐pelvic‐pain/ (last accessed July 2018)). As the guideline authors stated, careful consideration should be given when considering the applicability of these interventions in daily practice. For example, botulinum toxin A may not be easily accessible or acceptable for most men, since it involves an intraprostatic injection. As the GRADE Evidence to Decision Framework states, a careful evaluation of the patient's values and preferences, resource use and equity issues and the acceptability and feasibility of the interventions is warranted when drafting guidelines recommendations (Alonso‐Coello 2016); something that is beyond the scope of this review.

Quality of the evidence

The main limitations of the body of evidence were the following.

Study limitations: most studies had problems when masking the interventions from study personnel and participants. This is particularly important for this review, considering that all the predefined outcomes were subjective and participant‐reported. Many studies had a considerable amount of missing outcome data and there was little explanation as to how this was handled (e.g. using methods such as 'last observation carried forward'). Additionally, most studies poorly reported random sequence generation and allocation concealment, and most had no published protocol or analysis plan to assess the risk of selective reporting.
Inconsistency: we found considerable heterogeneity in some of the main comparisons; we were unable to explain this using our predefined sensitivity and subgroup analyses. We added a subgroup analysis based on one of our predefined conditions, but none of these analyses yielded significant results.
Imprecision: we estimated an optimal information size of 74 for the primary outcome 'prostatitis symptoms', and almost 50% of the studies had a smaller sample size; most studies therefore suffered from imprecision. Nevertheless, in some cases meta‐analysis of some of the included studies increased the number of participants for each comparison, overcoming this limitation. This was more difficult to do for the outcome 'adverse events', in which the small number of events (in some cases there were none) resulted in considerable imprecision.
Publication bias: we assessed the risk of publication bias using funnel plots in few outcomes, due to the paucity of trials, and we did not find evidence of any suggestive asymmetry.

Potential biases in the review process

We strictly followed our published protocol to reduce the risk of bias in the conduct of this review.

We performed a comprehensive search in multiple databases, trial registries and other sources to reduce the risk of meta‐bias in our review. We did not restrict the searches or inclusion of studies on the basis of language of publication. Thirty‐eight studies were written in a language other than English. We incorporated three additional authors (JHJ, SI, YX) who helped in the process of developing and writing this review by reading and processing the articles in Korean, Russian and Chinese. However, the assessment of the individual studies was done by a single author and this could have introduced errors in the process of developing the judgements for risk of bias and data extraction. We tried to minimise these errors by using computer‐assisted translation and thorough discussion of the extracted data with our co‐authors.

We were unable to retrieve some of the studies on traditional Chinese medicine (TCM) published in some Chinese journals (available at the China National Knowledge Infrastructure database) that were included in other reviews that searched Chinese databases (see Agreements and disagreements with other studies or reviews). Should we find the reports of these studies, we will evaluate them for inclusion in updates of this review, since we have no clear information about their eligibility. We note, however, that the reported results of these studies in the corresponding reviews are consistent with our findings.

We contacted study authors on multiple occasions with a variable rate of response. However, we acknowledge that many of the ratings of 'unclear' risk of bias were due to limitations in the report of the studies, rather than a true risk of bias in the conduct of these trials. We also contacted authors in order to obtain missing outcome data (e.g. standard deviation, number of participants, P values, etc.) with a poor response rate in most cases. We nevertheless report all available outcome data under "Studies not included in meta‐analysis or 'Summary of findings' table".

We deleted the 'Clinical Phenotyping' item as an intervention in our review, as suggested by a peer reviewer. We acknowledge that this strategy might not constitute in itself an intervention. This change has not affected the results of this review, since we found no trials on this subject. We also modified the presentation of some of the methods in this review (assessment of outcomes and GRADE methods), but this did not affect the results of the review either (see Differences between protocol and review).

We intended to explain the reasons for statistical heterogeneity across studies for many comparisons, but were unable to do so using our predefined and post hoc subgroup analyses. This led to the downgrading of our confidence in the evidence due to inconsistency, according to the GRADE criteria. We acknowledge that there is wide variability in the underlying causes and clinical manifestations of men suffering from this condition across studies, so we believe that there might be other variables that could explain this inconsistency. Given that the underlying cause of CP/CPPS remains unknown and may encompass different pathogenic pathways (Appiya 2019), unless there are clear distinctions of these pathways and different subtypes of CP/CPPS with common aetiologic and prognostic factors, we might expect that these inconsistencies across study populations of the different trials will persist.

Agreements and disagreements with other studies or reviews

We found several systematic reviews addressing interventions for CP/CPPS. These reviews had several methodological limitations: lack of a protocol stating the review methods, insufficiently comprehensive searches, inadequate language restrictions and no integration of the quality of the evidence with the results, for example, by using GRADE methods.

Cochrane Reviews

In a previous Cochrane Review on pregabalin for CP/CPPS (Aboumarzouk 2012) the authors included the same trial (Pontari 2010) as ours and reached similar conclusions, but we considered that the included study had low risk of bias, while the previous review considered it to be at high risk of bias. Our judgements are justified in the Characteristics of included studies section. Three systematic reviews (two of them Cochrane Reviews) included both pharmacological and non‐pharmacological interventions (McNaughton 2000; McNaughton Collins 1999; McNaughton 2002). We included some of the trials covered in these reviews. The findings on the effectiveness and the limitations of the quality of evidence were similar, but most of the included studies were from before 1999, when the Research Consensus defined the latest criteria for this condition (Nyberg 1999). For this reason, we performed a sensitivity analysis analysing this effect, as suggested by a peer reviewer of our previous review (Franco 2018).

Other reviews

In a comprehensive review, Anothaisintawee 2011 evaluated the effects of alpha blockers, antibiotics, anti‐inflammatories, finasteride, phytotherapy, pentosan, pregabalin and combined therapy and included the same trials as our review with similar results; however, this review stated that "the magnitude of apparent benefit with α‐blockers may be distorted by publication bias" which we did not find in our assessment.

Cai 2017 focused on the effects of pollen extract and included animal studies, non‐randomised studies and some of the clinical trials included in this review, with the same results. Two systematic reviews (Cohen 2012; Yang 2008) included the trials in this review but were underpowered for some comparisons, such as those including antibiotics and anti‐inflammatories. Yang 2008 included some trials only available at the China National Knowledge Infrastructure (CNKI).

A systematic review of TCM for chronic prostatitis (Chen 2006) included nine randomised trials from the CNKI database, none of which we included in this review. They found that there was low‐quality evidence that TCM was equivalent or superior to western therapies, but the meta‐analysis pooled randomised and non‐randomised studies. It is not clear if they included participants with bacterial prostatitis.

Erickson 2008 (and its update Le 2011) included some of the studies for pharmacological interventions for CP/CPPS. This review stated that 5‐alpha reductase inhibitors, allopurinol, alpha blockers, mepartricin, NSAIDs, pentosan, and quercetin may have little or no beneficial effect for this condition, but with great uncertainties because of the low quality of the body of evidence. While most findings in that review are similar to ours, the authors focused their analysis of alpha blockers on the largest study with low risk of bias. This agrees with our sensitivity analysis in which we found alpha blockers to be ineffective. Two other reviews (Lee 2007; Yang 2006) assessed the effect of alpha blockers, but their assessments of study quality were limited.

A systematic review with a network meta‐analysis (Qin 2016) assessed the effects of acupuncture, alpha blockers, antibiotics and combination therapy, including the same trials as this review with similar findings on effectiveness. The surface under the cumulative ranking (SUCRA) plot revealed interesting findings comparing non‐pharmacological therapies and pharmacological therapies, favouring acupuncture and electroacupuncture. Another review using network meta‐analysis (Thakkinstian 2012) also had similar findings but the authors reflected that "results are discrepant between the analyses of symptom scores and treatment responsiveness". We believe that this relates to the fact that difference symptom scores require smaller sample sizes than measurements of treatment effects for dichotomous outcomes. This is why most analyses for 'responders' were downgraded due to imprecision.

Magistro 2016 included similar trials but with a narrower scope, and the authors stated "Our current understanding of the pathophysiology underlying CP/CPPS resulting in this highly variable syndrome does not speak in favour of a monotherapy for management".

Authors' conclusions

Implications for practice.

We found low‐ to very low‐quality evidence that alpha blockers may reduce prostatitis symptoms based on a reduction of NIH‐CPSI scores greater than two (but less than eight) with an increased incidence of minor adverse events such as dizziness and hypotension. Other interventions such as antibiotics, anti‐inflammatories, intraprostatic botulinum A injection, traditional Chinese medicine, mepartricin and phosphodiesterase inhibitors may cause a reduction in prostatitis symptoms without an increased incidence of adverse events. Moderate‐quality evidence indicates that phytotherapy and 5‐alpha reductase inhibitors probably cause a small decrease in prostatitis symptoms and may not be associated with a greater incidence of adverse events.

Frequently we found few trials with active comparators and little evidence of the effects of these drugs on sexual dysfunction, quality of life or anxiety and depression.

Based on our uncertainty about the true effects of the wide variety of available interventions, the selection of the right pharmacological agent can be tailored based on different factors such as: the need to alleviate a predominant type of symptom, each agent's safety profile, the patient's values and preferences, and other contextual factors.

Implications for research.

Given the low‐quality evidence for most comparisons and outcomes included in this review, there is a need for additional research on the effects of some of the included interventions.These include:

future clinical trials should include a full report of their methods for greater transparency about potential sources of bias. Additionally, acknowledging the subjective nature of the participant‐reported outcomes that are critical for decision‐making, masking of these interventions is warranted, and providing information about the methods used to minimise attrition bias;
future studies should include a greater variety of outcomes, including sexual dysfunction, quality of life, and depression and anxiety, since this would represent the actual impact of these interventions on participants with CP/CPPS. Long‐term follow‐up is also needed, recognising the chronicity of this condition. It is also essential for studies to report the incidence of adverse events, to assess the net benefit of the interventions;
ideally, studies should include more than 74 participants to reduce the imprecision of the findings when considering prostatitis symptoms using the National Institute of Health ‐ Chronic Prostatitis Symptom Index (NIH‐CPSI) score. Larger sample sizes are required when assessing the number of responders to treatment or other outcomes;
considering the high comorbidity of participants with CP/CPPS, it is important for studies to include participants with comorbid conditions to assess subgroup effects.

Notes

We have based parts of the Methods section and Appendix 1 of this protocol on a standard template developed by the Cochrane Metabolic and Endocrine Disorders Group, which has been modified and adapted for use by the Cochrane Urology Group.

Acknowledgements

We thank the following individuals and organisations.

Cochrane Urology Group for providing guideline and templates for protocol and review development, especially Alea Miller, Robert Lane and Philipp Dahm, who provided close feedback and advice.
Instituto Universitario Hospital Italiano de Buenos Aires Cochrane Collaborating Centre, Argentina.
Family and Community Medicine Service and Urology Service, Hospital Italiano de Buenos Aires, Argentina.
Iván Solá and Jennifer Lyon for their contribution to the search strategy.
Jonathan Rees, Giuseppe Magistro and Florian Wagenlehner for their peer‐review input during the protocol stage. Prof. Wagenlehner also provided detailed information about the trials he directed. Ana Jerončić, H. Henry Lai, Dino Papeš and J. Curtis Nickel for their peer‐review input during the review stage.
Noriyuki Yamaji and Erika Ota from Cochrane Japan who translated and assessed the articles in Japanese.
Miwako Segawa from Cochrane Japan who provided some of the full‐text articles.
Jodi Schneider and Derek Ansel who provided some of the full‐text articles.
Derya Senturk, Bozyaka EAH, Izmir, who translated and assessed the articles in Turkish.
Curtis Nickel, Queen's University (Canada), provided a channel to continuously communicate the details of his vast research on this topic.

Appendices

Appendix 1. PubMed search strategy

#1 "Prostatitis"[Mesh]

#2 prostatit*[tiab]

#3 prostatodyn*[tiab]

#4 #1 OR #2 OR #3

#5 “Pelvic Pain"[Mesh]

#6 pelvic pain[tiab]

#7 CPP*[tiab]

#8 #5 OR #6 OR #7

#9 #4 AND #8

#10 "Asymptomatic Diseases"[Mesh]

#11 asymptom*[tiab]

#12 nonsymptom*[tiab]

#13 non symptom*[tiab]

#14 abacterial*[tiab]

#15 nonbacterial*[tiab]

#16 non bacterial*[tiab]

#17 aseptic*[tiab]

#18 nonseptic*[tiab]

#19 non septic*[tiab]

#20 #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19

#21 #4 AND #20

#22 chronic prostatitis chronic pelvic pain syndrome[tiab] OR CP CPP*[tiab]

#23 #9 OR #21 OR #22

#24 "Randomized Controlled Trial"[Publication Type]

#25 "Controlled Clinical Trial"[Publication Type]

#26 randomized[tiab]

#27 placebo[tiab]

#28 "drug therapy"[Subheading]

#29 randomly[tiab]

#30 trial[tiab]

#31 groups[tiab]

#32 #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31

#33 "Animals"[Mesh] NOT "Humans"[Mesh]

#34 #32 NOT #33

#35 #23 AND #34

Appendix 2. CENTRAL search strategy

#1 [mh prostatitis]

#2 prostatit*:ti,ab

#3 prostatodyn*:ti,ab

#4 #1 or #2 or #3

#5 [mh "pelvic pain"]

#6 pelvic near/3 pain:ti,ab

#7 CPP*:ti,ab

#8 #5 or #6 or #7

#9 #4 and #8

#10 [mh "asymptomatic diseases"]

#11 asymptom*:ti,ab

#12 nonsymptom*:ti,ab

#13 non near/3 symptom*:ti,ab

#14 abacterial*:ti,ab

#15 nonbacterial*:ti,ab

#16 non near/3 bacterial*:ti,ab

#17 aseptic*:ti,ab

#18 nonseptic*:ti,ab

#19 non near/3 septic*:ti,ab

#20 #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19

#21 #4 and #20

#22 prostatit* and (pelvic near/3 pain or CP CPP*)

#23 #9 or #21 or #22

Appendix 3. Embase search strategy

#1 “prostatitis”/exp

#2 prostatit*:ab,ti

#3 prostatodyn*:ab,ti

#4 #1 OR #2 OR #3

#5 “pelvic pain”/exp

#6 cpp*:ab,ti

#7 (pelvi* NEAR/3 pain):ab,ti

#8 #5 OR #6 OR #7

#9 #4 AND #8

#10 “asymptomatic disease”/exp

#11 asymptom*:ab,ti

#12 nonsymptom*:ab,ti

#13 (non NEAR/3 symptom*):ab,ti

#14 abacterial*:ab,ti

#15 nonbacterial*:ab,ti

#16 (non NEAR/3 bacterial*):ab,ti

#17 aseptic*:ab,ti

#18 nonseptic*:ab,ti

#19 (non NEAR/3 septic*):ab,ti

#20 #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18

OR #19

#21 #4 AND #20

#22 chronic:ab,ti AND (prostatitis NEAR/3 pelvi* NEAR/3 pain):ab,ti

#23 #9 OR #21 OR #22

#24 random*:ab,ti

#25 “clinical trial*”

#26 “health care quality”/exp

#27 #24 OR #25 OR #26

#28 #23 AND #27

Appendix 4. PsycINFO search strategy

1 prostatitis.mp.

2 prostatit*.ab,ti.

3 prostatodyn*.ab,ti

4 1 or 2 or 3

5 pelvic pain.mp.

6 (pelvi* adj3 pain).mp.

7 cpp*.ab,ti.

8 5 or 6 or 7

9 4 and 8

10 asymptom*.ab,ti.

11 nonsymptom*.ab,ti.

12 (non adj3 symptom*).ab,ti.

13 abacterial*.ab,ti.

14 nonbacterial*.ab,ti.

15 (non adj3 bacterial*).ab,ti.

16 aseptic*.ab,ti.

17 nonseptic*.ab,ti.

18 (non adj3 septic*).ab,ti.

19 10 or 12 or 13 or 14 or 15 or 16 or 17 or 18

20 4 and 19

21 (chronic prostatitis adj3 pelvi* adj3 pain).ab,ti.

22 9 or 20 or 21

Appendix 5. CINAHL search strategy

S1 MH “Prostatitis”

S2 TI prostatit* OR AB prostatit*

S3 TI prostatodyn* OR AB prostatodyn*

S4 S1 OR S2 OR S3

S5 MH “Pelvic Pain”

S6 TI pelvic pain OR AB pelvic pain

S7 TI cpp* OR AB cpp*

S8 S5 OR S6 OR S7

S9 S4 AND S8

S10 TI asymptom* OR AB asymptom*

S11 TI nonsymptom* OR AB nonsymptom*

S12 TI non N3 symptom* OR AB non N3 symptom*

S13 TI abacterial* OR AB abacterial*

S14 TI nonbacterial* OR AB nonbacterial*

S15 TI non N3 bacterial* OR AB non N3 bacterial*

S16 TI aseptic* OR AB aseptic*

S17 TI nonseptic* OR AB nonseptic*

S18 TI non N3 septic* OR AB non N3 septic*

S19 S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR

S18

S20 S4 AND S19

S21 TI chronic prostatitis/chronic pelvic pain syndrome OR chronic prostatitis

OR AB chronic prostatitis/chronic pelvic pain syndrome OR TI chronic

prostatitis chronic pelvic pain syndrome OR chronic prostatitis OR AB

chronic prostatitis chronic pelvic pain syndrome

S22 S9 OR S20 OR S21

Appendix 6. ClinicalTrials.gov/Controlled Trials/WHO ICTRP search strategy

Prostatitis AND (Pelvic Pain OR CPP OR CP CPPS)

Appendix 7. Abstract proceedings

Conference	Website (last access October 2017)
American Urology Association May 2017	www.jurology.com/issue/S0022‐5347(17)X0003‐7
American Urology Association May 2016	www.jurology.com/issue/S0022‐5347(16)X0004‐3
American Urology Association May 2015	www.jurology.com/issue/S0022‐5347(14)X0014‐5
European Association of Urology 2017	eau17.uroweb.org/
European Association of Urology 2016	eaumunich2016.uroweb.org/resource‐centre/
European Association of Urology 2015	Not accessible
Society of Sexual Medicine of North America 2017 annual meeting	www.smsna.org/V1/
Society of Sexual Medicine of North America 2016 annual meeting
Society of Sexual Medicine of North America 2015 annual meeting

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Data and analyses

Comparison 1. Alpha‐blockers versus placebo.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Prostatitis symptoms: short term	18	1524	Mean Difference (IV, Random, 95% CI)	‐5.01 [‐7.41, ‐2.61]
1.1 Terazosin	5	436	Mean Difference (IV, Random, 95% CI)	‐5.73 [‐10.96, ‐0.50]
1.2 Doxazosin	4	262	Mean Difference (IV, Random, 95% CI)	‐5.17 [‐11.50, 1.16]
1.3 Phenoxybenzamine	1	40	Mean Difference (IV, Random, 95% CI)	‐5.80 [‐7.91, ‐3.69]
1.4 Tamsulosin	4	302	Mean Difference (IV, Random, 95% CI)	‐5.89 [‐13.16, 1.38]
1.5 Alfuzosin	4	381	Mean Difference (IV, Random, 95% CI)	‐2.63 [‐4.55, ‐0.71]
1.6 Silodosin	1	103	Mean Difference (IV, Random, 95% CI)	‐3.60 [‐6.81, ‐0.39]
2 Prostatitis symptoms: pain	13	1243	Mean Difference (IV, Random, 95% CI)	‐2.39 [‐3.57, ‐1.22]
2.1 Terazosin	3	289	Mean Difference (IV, Random, 95% CI)	‐3.86 [‐6.00, ‐1.73]
2.2 Doxazosin	3	202	Mean Difference (IV, Random, 95% CI)	‐2.19 [‐4.56, 0.17]
2.3 Phenoxybenzamine	1	40	Mean Difference (IV, Random, 95% CI)	‐2.25 [‐3.78, ‐0.72]
2.4 Tamsulosin	3	265	Mean Difference (IV, Random, 95% CI)	‐3.17 [‐6.31, ‐0.03]
2.5 Alfuzosin	3	344	Mean Difference (IV, Random, 95% CI)	‐0.59 [‐1.67, 0.49]
2.6 Silodosin	1	103	Mean Difference (IV, Random, 95% CI)	‐1.40 [‐2.97, 0.17]
3 Prostatitis symptoms: urinary	13	1243	Mean Difference (IV, Random, 95% CI)	‐1.48 [‐2.29, ‐0.66]
3.1 Terazosin	3	289	Mean Difference (IV, Random, 95% CI)	‐2.07 [‐3.79, ‐0.34]
3.2 Doxazosin	3	202	Mean Difference (IV, Random, 95% CI)	‐1.71 [‐4.34, 0.92]
3.3 Phenoxybenzamine	1	40	Mean Difference (IV, Random, 95% CI)	‐1.60 [‐2.28, ‐0.92]
3.4 Tamsulosin	3	265	Mean Difference (IV, Random, 95% CI)	‐1.63 [‐3.85, 0.59]
3.5 Alfuzosin	3	344	Mean Difference (IV, Random, 95% CI)	‐0.67 [‐1.05, ‐0.29]
3.6 Silodosin	1	103	Mean Difference (IV, Random, 95% CI)	‐0.90 [‐2.00, 0.20]
4 Prostatitis symptoms: quality of life	13	1243	Mean Difference (IV, Random, 95% CI)	‐1.61 [‐2.49, ‐0.73]
4.1 Terazosin	3	289	Mean Difference (IV, Random, 95% CI)	‐2.51 [‐4.62, ‐0.40]
4.2 Doxazosin	3	202	Mean Difference (IV, Random, 95% CI)	‐1.34 [‐3.24, 0.56]
4.3 Phenoxybenzamine	1	40	Mean Difference (IV, Random, 95% CI)	‐2.2 [‐3.14, ‐1.26]
4.4 Tamsulosin	3	265	Mean Difference (IV, Random, 95% CI)	‐1.78 [‐4.96, 1.40]
4.5 Alfuzosin	3	344	Mean Difference (IV, Random, 95% CI)	‐0.53 [‐1.34, 0.29]
4.6 Silodosin	1	103	Mean Difference (IV, Random, 95% CI)	‐1.40 [‐2.49, ‐0.31]
5 Prostatitis symptoms: responders rate	7	721	Risk Ratio (M‐H, Random, 95% CI)	1.23 [0.94, 1.61]
5.1 Doxazosin	1	55	Risk Ratio (M‐H, Random, 95% CI)	0.90 [0.67, 1.20]
5.2 Tamsulosin	3	254	Risk Ratio (M‐H, Random, 95% CI)	1.49 [1.07, 2.06]
5.3 Alfuzosin	2	309	Risk Ratio (M‐H, Random, 95% CI)	1.82 [0.48, 6.80]
5.4 Silodosin	1	103	Risk Ratio (M‐H, Random, 95% CI)	1.09 [0.78, 1.52]
6 Prostatitis symptoms: long term	4	235	Mean Difference (IV, Random, 95% CI)	‐5.60 [‐10.89, ‐0.32]
6.1 Terazosin	1	51	Mean Difference (IV, Random, 95% CI)	‐7.76 [‐10.90, ‐4.62]
6.2 Tamsulosin	1	92	Mean Difference (IV, Random, 95% CI)	‐1.40 [‐2.73, ‐0.07]
6.3 Alfuzosin	1	35	Mean Difference (IV, Random, 95% CI)	‐3.4 [‐7.30, 0.50]
6.4 Doxazosin	1	57	Mean Difference (IV, Random, 95% CI)	‐9.7 [‐10.25, ‐9.15]
7 Prostatitis symptoms: long term	1	92	Risk Ratio (M‐H, Random, 95% CI)	1.57 [1.06, 2.32]
7.1 Tamsulosin	1	92	Risk Ratio (M‐H, Random, 95% CI)	1.57 [1.06, 2.32]
8 Adverse events	19	1588	Risk Ratio (M‐H, Random, 95% CI)	1.60 [1.09, 2.34]
8.1 Terazosin	6	431	Risk Ratio (M‐H, Random, 95% CI)	2.03 [1.14, 3.61]
8.2 Doxazosin	3	195	Risk Ratio (M‐H, Random, 95% CI)	1.47 [0.75, 2.88]
8.3 Phenoxybenzamine	1	40	Risk Ratio (M‐H, Random, 95% CI)	35.00 [2.25, 544.92]
8.4 Tamsulosin	5	367	Risk Ratio (M‐H, Random, 95% CI)	1.35 [0.60, 3.03]
8.5 Alfuzosin	4	452	Risk Ratio (M‐H, Random, 95% CI)	1.19 [0.37, 3.78]
8.6 Silodosin	1	103	Risk Ratio (M‐H, Random, 95% CI)	2.52 [1.15, 5.52]
9 Sexual dysfunction	4	452	Mean Difference (IV, Random, 95% CI)	0.26 [‐1.13, 1.65]
9.1 Terazosin	1	77	Mean Difference (IV, Random, 95% CI)	1.10 [‐0.84, 3.04]
9.2 Tamsulosin	1	99	Mean Difference (IV, Random, 95% CI)	‐0.20 [‐4.84, 4.44]
9.3 Alfuzosin	2	276	Mean Difference (IV, Random, 95% CI)	‐0.70 [‐2.89, 1.48]
10 Quality of life: mental	3	421	Mean Difference (IV, Random, 95% CI)	0.15 [‐2.63, 2.92]
10.1 Tamsulosin	1	90	Mean Difference (IV, Random, 95% CI)	‐1.00 [‐7.16, 1.16]
10.2 Alfuzosin	1	228	Mean Difference (IV, Random, 95% CI)	2.1 [‐0.64, 4.84]
10.3 Silodosin	1	103	Mean Difference (IV, Random, 95% CI)	0.30 [‐3.09, 3.69]
11 Quality of life: physical	3	421	Mean Difference (IV, Random, 95% CI)	1.17 [‐0.97, 3.30]
11.1 Tamsulosin	1	90	Mean Difference (IV, Random, 95% CI)	2.4 [‐0.52, 5.32]
11.2 Alfuzosin	1	228	Mean Difference (IV, Random, 95% CI)	‐0.5 [‐2.51, 1.51]
11.3 Silodosin	1	103	Mean Difference (IV, Random, 95% CI)	2.5 [‐0.81, 5.81]
12 Anxiety and depression	1	232	Mean Difference (IV, Random, 95% CI)	‐1.1 [‐2.54, 0.34]
12.1 Alfuzosin	1	232	Mean Difference (IV, Random, 95% CI)	‐1.1 [‐2.54, 0.34]
13 Urinary symptoms	2	143	Mean Difference (IV, Random, 95% CI)	‐2.68 [‐5.90, 0.54]
13.1 Terazosin	1	86	Mean Difference (IV, Random, 95% CI)	‐4.5 [‐6.64, ‐2.36]
13.2 Alfuzosin	1	57	Mean Difference (IV, Random, 95% CI)	‐1.20 [‐1.76, ‐0.64]
14 Prostatitis symptoms: responders rate (sensitivity analysis according to risk of bias)	2	155	Odds Ratio (M‐H, Random, 95% CI)	1.23 [0.61, 2.48]
14.1 Tamsulosin	2	155	Odds Ratio (M‐H, Random, 95% CI)	1.23 [0.61, 2.48]
15 Adverse events (sensitivity analysis according to risk of bias)	2	153	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.63, 1.47]
15.1 Tamsulosin	2	153	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.63, 1.47]
16 Prostatitis symptoms: short term (subgroup analysis by co‐interventions)	18	1524	Mean Difference (IV, Random, 95% CI)	‐5.01 [‐7.41, ‐2.61]
16.1 Without co‐interventions	7	688	Mean Difference (IV, Random, 95% CI)	‐3.56 [‐5.26, ‐1.86]
16.2 With co‐interventions (analgesics, antibiotics)	11	836	Mean Difference (IV, Random, 95% CI)	‐5.69 [‐8.90, ‐2.48]
17 Adverse events (subgroup analysis by co‐interventions)	19	1588	Risk Ratio (M‐H, Random, 95% CI)	1.60 [1.09, 2.34]
17.1 Without co‐interventions	11	1089	Risk Ratio (M‐H, Random, 95% CI)	1.69 [1.10, 2.60]
17.2 With co‐interventions (analgesics, antibiotics)	8	499	Risk Ratio (M‐H, Random, 95% CI)	1.20 [0.46, 3.17]

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Comparison 2. 5 alpha reductase inhibitors versus placebo.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Prostatitis symptoms	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2 Prostatitis symptoms: responder rate	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
3 Adverse events	2	105	Risk Ratio (M‐H, Random, 95% CI)	0.87 [0.33, 2.30]

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Comparison 3. Antibiotic therapy versus placebo.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Prostatitis symptoms	5	372	Mean Difference (IV, Random, 95% CI)	‐2.43 [‐4.72, ‐0.15]
1.1 Ciprofloxacin	3	215	Mean Difference (IV, Random, 95% CI)	‐1.69 [‐3.15, ‐0.23]
1.2 Levofloxacin	2	157	Mean Difference (IV, Random, 95% CI)	‐2.98 [‐9.41, 3.44]
2 Prostatitis symptoms: pain	4	319	Mean Difference (IV, Random, 95% CI)	‐0.92 [‐1.78, ‐0.06]
2.1 Ciprofloxacin	2	155	Mean Difference (IV, Random, 95% CI)	‐0.78 [‐1.86, 0.30]
2.2 Levofloxacin	2	164	Mean Difference (IV, Random, 95% CI)	‐0.72 [‐2.74, 1.30]
3 Prostatitis symptoms: urinary	4	319	Mean Difference (IV, Random, 95% CI)	‐0.12 [‐0.65, 0.41]
3.1 Ciprofloxacin	2	155	Mean Difference (IV, Random, 95% CI)	‐0.29 [‐1.17, 0.58]
3.2 Levofloxacin	2	164	Mean Difference (IV, Random, 95% CI)	0.13 [‐0.85, 1.11]
4 Prostatitis symptoms: quality of life	4	319	Mean Difference (IV, Random, 95% CI)	‐0.45 [‐0.91, 0.02]
4.1 Ciprofloxacin	2	155	Mean Difference (IV, Random, 95% CI)	‐0.44 [‐1.04, 0.15]
4.2 Levofloxacin	2	164	Mean Difference (IV, Random, 95% CI)	‐0.50 [‐1.52, 0.53]
5 Prostatitis symptoms: responder rate	2	178	Risk Ratio (M‐H, Random, 95% CI)	1.12 [0.73, 1.74]
5.1 Ciprofloxacin	1	98	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.48, 2.09]
5.2 Levofloxacin	1	80	Risk Ratio (M‐H, Random, 95% CI)	1.20 [0.70, 2.05]
6 Adverse events	4	336	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.66, 1.55]
6.1 Ciprofloxacin	1	95	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.60, 1.57]
6.2 Levofloxacin	3	241	Risk Ratio (M‐H, Random, 95% CI)	1.17 [0.46, 2.97]
7 Sexual dysfunction	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
7.1 Levofloxacin	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8 Quality of life: mental	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
8.1 Ciprofloxacin	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Quality of life: physical	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
9.1 Ciprofloxacin	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
10 Urinary symptoms	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
10.1 Ciprofloxacin	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
11 Prostatitis symptoms: subgroup analysis (age)	5	372	Mean Difference (IV, Random, 95% CI)	‐2.43 [‐4.72, ‐0.15]
11.1 Mean age > 50 years old	1	80	Mean Difference (IV, Random, 95% CI)	0.60 [‐3.79, 4.99]
11.2 Mean age < 50 years old	4	292	Mean Difference (IV, Random, 95% CI)	‐2.92 [‐5.37, ‐0.46]
12 Adverse events: subgroup analysis (age)	4	336	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.66, 1.55]
12.1 Mean age > 50 years old	1	80	Risk Ratio (M‐H, Random, 95% CI)	1.17 [0.46, 2.97]
12.2 Mean age < 50 years old	3	256	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.60, 1.57]
13 Prostatitis symptoms: subgroup analysis (co‐interventions)	5	372	Mean Difference (IV, Random, 95% CI)	‐2.43 [‐4.72, ‐0.15]
13.1 Without co‐interventions	2	167	Mean Difference (IV, Random, 95% CI)	‐1.57 [‐4.77, 1.63]
13.2 With co‐interventions (alpha blockers)	3	205	Mean Difference (IV, Random, 95% CI)	‐2.96 [‐6.28, 0.37]
14 Adverse events: subgroup analysis (co‐interventions)	4	336	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.66, 1.55]
14.1 Without co‐interventions	2	175	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.66, 1.55]
14.2 With co‐interventions (alpha blockers)	2	161	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

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Comparison 4. Antiinflammatories versus placebo.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Prostatitis symptoms	7	585	Mean Difference (IV, Random, 95% CI)	‐2.50 [‐3.74, ‐1.26]
1.1 Corticosteroids	1	158	Mean Difference (IV, Random, 95% CI)	‐2.82 [‐4.10, ‐1.54]
1.2 Nonsteroidal anti‐inflammatory drugs	5	369	Mean Difference (IV, Random, 95% CI)	‐2.56 [‐4.50, ‐0.62]
1.3 Thiocolchicoside and ibuprofen	1	58	Mean Difference (IV, Random, 95% CI)	‐1.5 [‐2.10, ‐0.90]
2 Prostatitis symptoms: pain	6	497	Mean Difference (IV, Random, 95% CI)	‐2.28 [‐4.08, ‐0.48]
2.1 Corticosteroids	1	158	Mean Difference (IV, Random, 95% CI)	‐1.67 [‐1.96, ‐1.38]
2.2 Nonsteroidal anti‐inflammatory drugs	3	265	Mean Difference (IV, Random, 95% CI)	‐1.80 [‐3.80, 0.20]
2.3 Antileukotriene	1	17	Mean Difference (IV, Random, 95% CI)	1.60 [‐5.79, 8.99]
2.4 Thiocolchicoside and ibuprofen	1	57	Mean Difference (IV, Random, 95% CI)	‐5.2 [‐5.59, ‐4.81]
3 Prostatitis symptoms: urinary	6	497	Mean Difference (IV, Random, 95% CI)	‐0.75 [‐1.53, 0.03]
3.1 Corticosteroids	1	158	Mean Difference (IV, Random, 95% CI)	‐0.69 [‐0.88, ‐0.50]
3.2 Nonsteroidal anti‐inflammatory drugs	3	265	Mean Difference (IV, Random, 95% CI)	‐0.38 [‐0.64, ‐0.13]
3.3 Antileukotriene	1	17	Mean Difference (IV, Random, 95% CI)	0.60 [‐0.84, 2.04]
3.4 Thiocolchicoside and ibuprofen	1	57	Mean Difference (IV, Random, 95% CI)	‐3.00 [‐3.47, ‐2.53]
4 Prostatitis symptoms: quality of life	6	497	Mean Difference (IV, Random, 95% CI)	‐1.25 [‐2.58, 0.08]
4.1 Corticosteroids	1	158	Mean Difference (IV, Random, 95% CI)	‐0.5 [‐0.75, ‐0.25]
4.2 Nonsteroidal anti‐inflammatory drugs	3	265	Mean Difference (IV, Random, 95% CI)	‐0.45 [‐0.90, 0.01]
4.3 Antileukotriene	1	17	Mean Difference (IV, Random, 95% CI)	‐0.40 [‐4.86, 4.06]
4.4 Thiocolchicoside and ibuprofen	1	57	Mean Difference (IV, Random, 95% CI)	‐4.5 [‐5.02, ‐3.98]
5 Prostatitis symptoms: responder rate	2	82	Risk Ratio (M‐H, Random, 95% CI)	1.44 [0.68, 3.03]
5.1 Corticosteroids	1	18	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.25, 4.00]
5.2 Nonsteroidal anti‐inflammatory drugs	1	64	Risk Ratio (M‐H, Random, 95% CI)	1.67 [0.69, 4.04]
6 Prostatitis symptoms: long term	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.1 Thiocolchicoside and ibuprofen	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
7 Adverse events	7	540	Risk Ratio (M‐H, Random, 95% CI)	1.27 [0.81, 2.00]
7.1 Corticosteroids	1	160	Risk Ratio (M‐H, Random, 95% CI)	5.00 [0.24, 102.53]
7.2 Nonsteroidal anti‐inflammatory drugs	4	303	Risk Ratio (M‐H, Random, 95% CI)	1.85 [0.79, 4.32]
7.3 Antileukotriene	1	17	Risk Ratio (M‐H, Random, 95% CI)	0.56 [0.23, 1.37]
7.4 Thiocolchicoside and ibuprofen	1	60	Risk Ratio (M‐H, Random, 95% CI)	1.42 [0.83, 2.43]
8 Urinary symptoms	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
8.1 Nonsteroidal anti‐inflammatory drugs	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Prostatitis symptoms: subgroup analysis (co‐interventions)	7	585	Mean Difference (IV, Random, 95% CI)	‐2.50 [‐3.74, ‐1.26]
9.1 Without co‐interventions	1	64	Mean Difference (IV, Random, 95% CI)	‐3.62 [‐4.85, ‐2.39]
9.2 With co‐interventions	6	521	Mean Difference (IV, Random, 95% CI)	‐2.29 [‐3.67, ‐0.90]
10 Adverse events	7	540	Risk Ratio (M‐H, Random, 95% CI)	1.27 [0.81, 2.00]
10.1 Without co‐interventions	1	64	Risk Ratio (M‐H, Random, 95% CI)	2.0 [0.19, 20.97]
10.2 With co‐interventions	6	476	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.73, 2.15]

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Comparison 5. Phytotherapy versus placebo.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Prostatitis symptoms	5	320	Mean Difference (IV, Random, 95% CI)	‐5.02 [‐6.81, ‐3.23]
1.1 Pollen extract vs. placebo	1	137	Mean Difference (IV, Random, 95% CI)	‐2.5 [‐4.44, ‐0.56]
1.2 Prolit Super Septo versus placebo	1	57	Mean Difference (IV, Random, 95% CI)	‐9.0 [‐16.81, ‐1.19]
1.3 Calendula‐Curcuma versus placebo	1	48	Mean Difference (IV, Random, 95% CI)	‐6.0 [‐7.28, ‐4.72]
1.4 Quercetin (flavonoid) versus placebo	1	28	Mean Difference (IV, Random, 95% CI)	‐5.80 [‐10.80, ‐0.80]
1.5 Add‐on cranberry compared to standard care	1	50	Mean Difference (IV, Random, 95% CI)	‐5.40 [‐7.51, ‐3.29]
2 Prostatitis symptoms: pain subscore	5	431	Mean Difference (IV, Random, 95% CI)	‐1.42 [‐1.99, ‐0.85]
2.1 Pollen extract vs. placebo	2	296	Mean Difference (IV, Random, 95% CI)	‐1.30 [‐2.05, ‐0.55]
2.2 Prolit Super Septo versus placebo	1	57	Mean Difference (IV, Random, 95% CI)	‐4.0 [‐13.31, 5.31]
2.3 Quercetin (flavonoid) versus placebo	1	28	Mean Difference (IV, Random, 95% CI)	‐2.8 [‐5.41, ‐0.19]
2.4 Add‐on cranberry compared to standard care	1	50	Mean Difference (IV, Random, 95% CI)	‐1.40 [‐2.34, ‐0.46]
3 Prostatitis symptoms: urinary symptoms	5	431	Mean Difference (IV, Random, 95% CI)	‐0.99 [‐1.75, ‐0.23]
3.1 Pollen Extract vs. Placebo	2	296	Mean Difference (IV, Random, 95% CI)	‐0.49 [‐1.15, 0.16]
3.2 Prolit Super Septo versus placebo	1	57	Mean Difference (IV, Random, 95% CI)	‐1.30 [‐6.15, 3.55]
3.3 Quercetin (flavonoid) versus placebo	1	28	Mean Difference (IV, Random, 95% CI)	‐1.5 [‐3.27, 0.27]
3.4 Add‐on cranberry compared to standard care	1	50	Mean Difference (IV, Random, 95% CI)	‐1.80 [‐2.47, ‐1.13]
4 Prostatitis symptoms: quality of life	5	431	Mean Difference (IV, Random, 95% CI)	‐1.60 [‐2.30, ‐0.90]
4.1 Pollen Extract vs. Placebo	2	296	Mean Difference (IV, Random, 95% CI)	‐1.09 [‐1.66, ‐0.51]
4.2 Prolit Super Septo versus placebo	1	57	Mean Difference (IV, Random, 95% CI)	‐3.70 [‐9.12, 1.72]
4.3 Quercetin (flavonoid) versus placebo	1	28	Mean Difference (IV, Random, 95% CI)	‐1.90 [‐3.97, 0.17]
4.4 Add‐on cranberry compared to standard care	1	50	Mean Difference (IV, Random, 95% CI)	‐2.2 [‐2.75, ‐1.65]
5 Prostatitis symptoms: responder rate	3	224	Risk Ratio (M‐H, Random, 95% CI)	1.78 [1.25, 2.52]
5.1 Pollen extract vs. placebo	1	137	Risk Ratio (M‐H, Random, 95% CI)	1.47 [1.05, 2.05]
5.2 Prolit Super Septo versus placebo	1	57	Risk Ratio (M‐H, Random, 95% CI)	2.02 [1.23, 3.32]
5.3 Quercetin (flavonoid) versus placebo	1	30	Risk Ratio (M‐H, Random, 95% CI)	3.33 [1.14, 9.75]
6 Adverse events	7	540	Risk Ratio (M‐H, Random, 95% CI)	1.13 [0.54, 2.36]
6.1 Pollen Extract vs. Placebo	3	357	Risk Ratio (M‐H, Random, 95% CI)	1.14 [0.34, 3.79]
6.2 Prolit Super Septo versus placebo	1	57	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.3 Calendula‐Curcuma versus placebo	1	48	Risk Ratio (M‐H, Random, 95% CI)	3.00 [0.13, 70.16]
6.4 Quercetin (flavonoid) versus placebo	1	28	Risk Ratio (M‐H, Random, 95% CI)	1.73 [0.18, 16.99]
6.5 Add‐on cranberry compared to standard care	1	50	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7 Sexual dysfunction	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
7.1 Calendula‐Curcuma versus placebo	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8 Urinary symptoms	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
8.1 Pollen Extract vs. Placebo	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Prostatitis symptoms: subgroup analysis (co‐interventions)	5	320	Mean Difference (IV, Random, 95% CI)	‐5.02 [‐6.81, ‐3.23]
9.1 Without co‐interventions	3	133	Mean Difference (IV, Random, 95% CI)	‐6.06 [‐7.28, ‐4.84]
9.2 With co‐interventions	2	187	Mean Difference (IV, Random, 95% CI)	‐3.92 [‐6.76, ‐1.08]
10 Adverse events: subgroup analysis (co‐interventions)	7	540	Risk Ratio (M‐H, Random, 95% CI)	1.13 [0.54, 2.36]
10.1 Without co‐interventions	4	191	Risk Ratio (M‐H, Random, 95% CI)	2.09 [0.33, 13.30]
10.2 With co‐interventions	3	349	Risk Ratio (M‐H, Random, 95% CI)	1.14 [0.34, 3.79]

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Comparison 6. Botulinum toxin A versus placebo.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Prostatitis symptoms	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
1.1 Intraprostatic	1	60	Mean Difference (IV, Random, 95% CI)	‐25.80 [‐30.15, ‐21.45]
1.2 Pelvic floor muscles	1	29	Mean Difference (IV, Random, 95% CI)	‐2.6 [‐5.59, 0.39]
2 Prostatitis symptoms: pain subscore	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
2.1 Intraprostatic	1	60	Mean Difference (IV, Random, 95% CI)	‐14.63 [‐16.76, ‐12.50]
2.2 Pelvic floor muscles	1	29	Mean Difference (IV, Random, 95% CI)	‐1.70 [‐3.23, ‐0.17]
3 Prostatitis symptoms: urinary subscore	2	89	Mean Difference (IV, Random, 95% CI)	‐2.82 [‐7.40, 1.76]
3.1 Intraprostatic	1	60	Mean Difference (IV, Random, 95% CI)	‐5.17 [‐6.72, ‐3.62]
3.2 Pelvic floor muscles	1	29	Mean Difference (IV, Random, 95% CI)	‐0.5 [‐1.85, 0.85]
4 Prostatitis symptoms: quality of life	2		Mean Difference (IV, Random, 95% CI)	Totals not selected
4.1 Intraprostatic	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
4.2 Pelvic floor muscles	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
5 Adverse events	2	89	Risk Ratio (M‐H, Random, 95% CI)	5.00 [0.25, 99.95]
5.1 Intraprostatic	1	60	Risk Ratio (M‐H, Random, 95% CI)	5.00 [0.25, 99.95]
5.2 Pelvic floor muscle	1	29	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6 Urinary symptoms	1	60	Mean Difference (IV, Random, 95% CI)	‐9.67 [‐13.97, ‐5.37]
6.1 Intraprostatic	1	60	Mean Difference (IV, Random, 95% CI)	‐9.67 [‐13.97, ‐5.37]

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Comparison 7. Allopurinol versus placebo.

Outcome or subgroup title	No. of studies	Statistical method	Effect size
1 Prostatitis symptoms	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
2 Prostatitis symptoms: pain subscore	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
3 Prostatitis symptoms: urinary subscore	1	Mean Difference (IV, Random, 95% CI)	Totals not selected

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Comparison 8. Traditional chinese medicine versus placebo or usual care.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Prostatitis symptoms	7	835	Mean Difference (IV, Random, 95% CI)	‐3.13 [‐4.99, ‐1.28]
1.1 Prostant versus placebo	2	164	Mean Difference (IV, Random, 95% CI)	‐3.93 [‐7.76, ‐0.10]
1.2 Qianlieping (add‐on) versus medical treatment alone	1	154	Mean Difference (IV, Random, 95% CI)	‐3.40 [‐5.03, ‐1.77]
1.3 Qianlieantong (add‐on) versus medical treatment alone	1	115	Mean Difference (IV, Random, 95% CI)	‐6.67 [‐8.14, ‐5.20]
1.4 Yuleshu (add‐on) versus medical care alone	1	88	Mean Difference (IV, Random, 95% CI)	‐1.41 [‐2.57, ‐0.25]
1.5 Aike Mixture versus placebo	1	74	Mean Difference (IV, Random, 95% CI)	‐3.59 [‐8.24, 1.06]
1.6 Bazhengsan versus placebo	2	162	Mean Difference (IV, Random, 95% CI)	‐1.53 [‐9.28, 6.23]
1.7 Prostatitis Decoction versus placebo	1	78	Mean Difference (IV, Random, 95% CI)	1.07 [‐3.78, 5.92]
2 Prostatitis symptoms: pain subscore	5	585	Mean Difference (IV, Random, 95% CI)	‐1.49 [‐2.44, ‐0.53]
2.1 Prostant versus placebo	2	164	Mean Difference (IV, Random, 95% CI)	‐1.42 [‐2.51, ‐0.34]
2.2 Qianlieantong versus medical treatment alone	1	115	Mean Difference (IV, Random, 95% CI)	‐2.54 [‐3.24, ‐1.84]
2.3 Yuleshu versus medical care	1	88	Mean Difference (IV, Random, 95% CI)	‐2.52 [‐3.64, ‐1.40]
2.4 Aike Mixture versus placebo	1	74	Mean Difference (IV, Random, 95% CI)	‐2.21 [‐4.60, 0.18]
2.5 Bazhengsan versus placebo	1	66	Mean Difference (IV, Random, 95% CI)	1.35 [‐1.22, 3.92]
2.6 Prostatitis Decoction versus placebo	1	78	Mean Difference (IV, Random, 95% CI)	1.02 [‐1.52, 3.56]
3 Prostatitis symptoms: urinary subscore	4	497	Mean Difference (IV, Random, 95% CI)	‐0.78 [‐1.50, ‐0.06]
3.1 Prostant versus placebo	2	164	Mean Difference (IV, Random, 95% CI)	‐1.62 [‐3.37, 0.13]
3.2 Qianlieantong versus medical treatment alone	1	115	Mean Difference (IV, Random, 95% CI)	‐0.39 [‐1.02, 0.24]
3.3 Aike Mixture versus placebo	1	74	Mean Difference (IV, Random, 95% CI)	‐0.84 [‐2.31, 0.63]
3.4 Bazhengsan versus placebo	1	66	Mean Difference (IV, Random, 95% CI)	0.25 [‐1.35, 1.85]
3.5 Prostatitis Decoction versus placebo	1	78	Mean Difference (IV, Random, 95% CI)	‐0.26 [‐1.73, 1.21]
4 Prostatitis symptoms: quality of life	2	306	Mean Difference (IV, Random, 95% CI)	‐0.97 [‐2.14, 0.20]
4.1 Prostant versus placebo	1	88	Mean Difference (IV, Random, 95% CI)	‐1.91 [‐1.00, ‐0.82]
4.2 Aike Mixture versus placebo	1	74	Mean Difference (IV, Random, 95% CI)	‐1.10 [‐3.36, 1.16]
4.3 Bazhengsan versus placebo	1	66	Mean Difference (IV, Random, 95% CI)	0.66 [‐1.65, 2.97]
4.4 Prostatitis Decoction versus placebo	1	78	Mean Difference (IV, Random, 95% CI)	‐0.34 [‐2.59, 1.91]
5 Adverse events	4	584	Risk Ratio (M‐H, Random, 95% CI)	1.34 [0.22, 8.02]
5.1 Prostant versus placebo	2	212	Risk Ratio (M‐H, Random, 95% CI)	0.72 [0.03, 19.50]
5.2 Qianlieping versus medical treatment alone	1	154	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.3 Aike Mixture versus placebo	1	74	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.4 Bazhengsan versus placebo	1	66	Risk Ratio (M‐H, Random, 95% CI)	4.33 [0.26, 72.96]
5.5 Prostatitis Decoction versus placebo	1	78	Risk Ratio (M‐H, Random, 95% CI)	2.43 [0.14, 42.93]
6 Sexual dysfunction	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.1 Yuleshu versus medical care	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
7 Anxiety and depression: anxiety	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
7.1 Yuleshu versus medical care	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8 Anxiety and depression: depression	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
8.1 Yuleshu versus medical care	1		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

Abdalla 2018.

Methods	Study design: Parallel‐group randomised controlled trial Study dates: not available Setting: outpatient ‐ possibly single centre ‐ international Country: Saudi Arabia
Participants	Inclusion criteria: "with national Institutes of Health (NIH) diagnosis of category III CP/CPPS, but without erectile dysfunction" Exclusion criteria: Not available Sample size: 108 randomised participants. Age (mean in years ±SD): Group 1 41.3 (SD 4.2); Group 2 39.8 (SD 5.1) Baseline NIH‐CPSI score: Not available All participants were men
Interventions	Group 1 (n = 54): levofloxacin 500 mg daily, 4 weeks Group 2 (n = 54): levofloxacin 500 mg daily, plus tadalafil 5 mg daily; 4 weeks Co‐interventions: no other co‐interventions described
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI questionnaire Time points measured: 4 weeks Time points reported: 4 weeks Sexual dysfunction How measured: IIEF score Time points measured: 4 weeks Time points reported: 4 weeks Adverse events How measured: Narratively
Funding sources	None
Declarations of interest	Not available
Notes	Study available as abstract only
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not available (abstract only)
Allocation concealment (selection bias)	Unclear risk	Not available (abstract only)
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	Not available (abstract only)
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	Not available (abstract only)
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Not available (abstract only)
Selective reporting (reporting bias)	Unclear risk	Not available (abstract only)
Other bias	Unclear risk	Not available (abstract only)

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Alexander 2004.

Methods	Study design: Parallel‐group randomised controlled trial with factorial design Study dates: start date July 2001 ‐ end date June 2002abstract Setting: outpatient ‐ multicentre 10 tertiary medical centres ‐ international Country: USA and Canada
Participants	Inclusion criteria: men with symptoms of discomfort or pain in the pelvic region for at least a 3‐month period within the previous 6 months. Candidates must have at least a “moderate” overall score on the NIH‐CPSI defined as 15 or more points of a potential of 0 to 43 points Exclusion criteria: any prostate, bladder, or urethral cancer, seizure disorder; concurrent Inflammatory bowel disease; active urethral stricture; neurologic disease or disorder affecting the bladder; liver disease; neurologic impairment or psychiatric disorder preventing understanding of consent and ability to comply with protocol. Prior 12 mo: Diagnosed with or treated for symptomatic genital herpes. Prior 3 mo: urinary tract infection with a urine culture value of 100,000 CFU/mL; clinical evidence of urethritis, including urethral discharge or positive culture, diagnostic of sexually transmitted diseases (including gonorrhoea, chlamydia, mycoplasma or trichomonas, but not including HIV/AIDS); symptoms of acute or chronic epididymitis. Prior treatments: any pelvic radiation, systemic chemotherapy; intravesical chemotherapy; intravesical BCG, transurethral procedures, balloon dilation of the prostate, open prostatectomy or any other prostate surgery or treatment such as cryotherapy or thermal therapy; prior treatment for orchialgia without pelvic symptoms; known allergy or sensitivity to ciprofloxacin hydrochloride, tamsulosin hydrochloride, or any of their known components. Prior 3 mo: Prostate biopsy Sample size: 196 randomised participants. Age (mean in years ±SD): Group 1 = 42.6 (SD 12.0); Group 2 = 45.9 (SD 11.7); Group 3 = 45.3 (SD 9.7); Group 4 = 44.5 (SD 11.4) Baseline NIH‐CPSI score: Group 1 = 25 (SD 5.1), Group 2 = 24.2 (SD 6.2), Group 3 = 24.6 (SD 6.2), Group 4 = 25.3 (SD 6.1) All participants were men
Interventions	Group 1 (n = 49): ciprofloxacin placebo, 1 tablet, twice daily, plus tamsulosin placebo, 1 tablet daily; 6 weeks Group 2 (n = 49): ciprofloxacin 500 mg, 1 tablet, twice daily, plus tamsulosin placebo, 1 tablet daily; 6 weeks Group 3 (n = 49): ciprofloxacin placebo, 1 tablet, twice daily, plus tamsulosin 0.4 mg, 1 tablet daily; 6 weeks Group 4 (n = 49): ciprofloxacin 500 mg, 1 tablet, twice daily, plus tamsulosin 0.4 mg, 1 tablet daily; 6 weeks Co‐interventions: no co‐interventions described
Outcomes	Prostatitis Symptoms How measured: with NIH‐CPSI questionnaire, total score and subscores measurements Time points measured: 2 at baseline screening (1 to 3 weeks apart), and every 3 weeks until 12 weeks. Time points reported: change from baseline at 6 weeks (Figure 2 shows means for week 0‐3‐6‐9‐12) Quality of life How measured:Medical Outcomes Study 12‐items Short‐Form Survey Time points measured: not stated Time points reported: change from baseline at 6 weeks Adverse events How measured: National Cancer Institute Common Toxicity Criteria classification, open‐ended questions Time points measured: "throughout the study" ‐ at each contact Time points reported: cumulative report at 6 weeks
Funding sources	National Institute of Health cooperative agreement. Boehringer Ingelheim provided tamsulosin and matching placebo. Bayer Corporation provided ciprofloxacin and matching placebo
Declarations of interest	Grant by National Institutes of Health cooperative agreements U01 DK53572, U01 DK53730, U01 DK53736, U01 DK53734, U01 DK53732, U01 DK53746, and U01 DK53738. Boehringer Ingelheim provided tamsulosin and matching placebo; Bayer Corporation provided ciprofloxacin and matching placebo. Authors: Nickel, Zeitlin, Alexander, Shoskes have received honoraria from the aforementioned Pharmaceuticals
Notes	The study reported a 7‐point patient‐reported global response assessment at 6 weeks. Results are presented per group individually and per factor (group ciprofloxacin vs placebo; group tamsulosin vs placebo) Contact information: Dr. Alexander: Urology (112), Veterans Affairs Maryland Health Care System, 10 North Greene Street, Baltimore, MD 21201.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Each patient was randomly assigned by computer"
Allocation concealment (selection bias)	Low risk	Quote: "The research pharmacist at each site provided the blinded study drugs in 2 tamper‐evident bottles."
Blinding of participants and personnel (performance bias)   Subjective outcomes	Low risk	Quote: "All clinical investigators, research nurses, and patients were blinded to treatment assignments until all patients had completed follow‐up."
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Quote: "All clinical investigators, research nurses, and patients were blinded to treatment assignments until all patients had completed follow‐up."
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: "174 men (89%) were available for evaluation at 6 weeks [...]. Another 3 participants withdrew from study follow‐up between 6 and 12 week"
Selective reporting (reporting bias)	Low risk	All prespecified outcomes in the published protocol (Alexander 2004) were reported
Other bias	Low risk	No other sources of bias were identified

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Apolikhin 2010.

Methods	Study design: Parallel‐group randomised trial Study dates: 2008 (start and end date) Setting: outpatient, multicentre, national Country: Russia
Participants	Inclusion criteria: age 18 ‐ 50; diagnosis of CP/CPPS (type IIIa) for 6 months and more; NIH‐CPSI baseline pain score ≥ 3 Exclusion criteria: postoperative patients in urogenital area; patients with neurogenic bladder dysfunctions, cervical sclerosis of urethra, urethral stricture, prostate hyperplasia, bladder cancer, prostate cancer, bladder diverticulosis; infection of urogenital tract, medication that is known to affect urination prior to study, diseases known to alternate biochemical indices twofold and more (decrease/increase) Sample size: 78 participants were enrolled and randomised Age (years): Group 1 mean = 34.8 (SD = 8.79); Group 2 mean = 39,0 (SD = 7.49) NIH‐CPSI baseline score (obtained from the graph): Group 1 mean = 20.0 (SE = 1.0) Group 2 mean = 25.0 (SE = 0.5) All participants were men
Interventions	Group 1 (n = 55): Cernilton (pollen extract) 2 pills 3 times/day, orally, for 3 months Group 2 (n = 23): Cernilton (pollen extract) 1 pills 3 times/day, orally, for 3 months Co‐interventions: no co‐interventions described
Outcomes	Prostatitis Symptoms How measured: NIH‐total score Time points measured: baseline, 3 months, 6 months Time points reported: baseline, 3 months, 6 months
Funding sources	none
Declarations of interest	none
Notes	The urinary symptoms as measured by IPSS scale were Intended according to Methods section but it was not possible to Identify the findings throughout the article. This article was written in Russian Contact information: apolikhin.oleg@yahoo.com (the author provided the full text of the study)
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available
Allocation concealment (selection bias)	Unclear risk	No information available
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Participants and personnel were not blinded. After randomisation both groups were allotted 3‐month pack of Cernilton
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Participants and personnel were not blinded. After randomisation both groups were allotted 3‐month pack of Cernilton
Incomplete outcome data (attrition bias)   All outcomes	Low risk	There are no missing outcome data (all outcomes)
Selective reporting (reporting bias)	High risk	The symptoms as measured by IPSS scale was Intended according to Methods section but It was not possible to Identify the findings throughout the article. The variance of resulting figures was only reported graphically
Other bias	Low risk	No other sources of bias were identified

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Bates 2007.

Methods	Study design: Parallel‐group randomised trial Study dates: start date July 2000 ‐ end date August 2002 Setting: outpatient – single centre‐ national Country: United Kindom
Participants	Inclusion criteria: all patients aged 18 – 65 years, with CPPS (inflammatory or non‐inflammatory) for ≥ 6 months and who had failed to improve with standard antibiotic therapy; negative infection screen, including the 4‐glass test and bacterial location studies; normal urological investigations; normal liver function tests, urea and electrolytes, full blood count and erythrocyte sedimentation ratio Exclusion criteria: contraindication to steroid therapy Sample size: 21 Age (years): Group 1 = 43.0 (10.7) Group 2 = 39.1 (10.1) Baseline NIH‐CPSI score: Group 1 = 25.5 (SD 7.6) Group 2 23.4 (SD 5.8) All participants were men
Interventions	Group 1 (n = 9): prednisolone 20 mg (4 capsules) once daily for 7 days, then 15 mg (3 capsules) once daily for 7 days, 10 mg (2 capsules) once daily for 7 days, finishing with 5 mg (1 capsule) once daily for 7 days Group 2 (n = 12): matched placebo Co‐interventions: no information available
Outcomes	Prostatitis symptoms How measured: NIH‐CPSI score Time points measured: baseline, 1, 3, 6 and 12 months Time points reported: baseline and 3 months (P values) Quality of life How measured: General Health Questionnaire (GHQ‐30) Time points measured: baseline, 1, 3, 6 and 12 months Time points reported: not reported Anxiety and depression How measured: Hospital Anxiety and Depression Scale (HADS) Time points measured: baseline, 1, 3, 6 and 12 months Time points reported: baseline and 3 months (P values)
Funding sources	Quote:“STH NHS FT Research Department – Small Grants award scheme. A grant for this study was provided by Central Sheffield University Hospitals Research Department, Royal Hallamshire Hospital, Sheffield, under the Pilot Project Research Scheme.”
Declarations of interest	None declared
Notes	The authors stated that the participants did not fill the GHQ‐30 at follow‐up as planned Contact information: Sylvia.bates@sth.nhs.uk; sylviabates@yahoo.co.uk
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. We wrote to study authors
Allocation concealment (selection bias)	Low risk	Quote: “Randomization was undertaken by the dispensing pharmacy, and hence both the participants and the investigator were unaware of the allocation.”
Blinding of participants and personnel (performance bias)   Subjective outcomes	Low risk	Quote: “both the participants and the investigator were unaware of the allocation.”
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Quote: “both the participants and the investigator were unaware of the allocation.”
Incomplete outcome data (attrition bias)   All outcomes	High risk	All outcomes: 3/9 patients were excluded from the experimental arm analysis due to the use of antibiotics or lack of improvement of symptoms (none in the control group). Not all participants filled the GHQ‐30 questionnaire
Selective reporting (reporting bias)	High risk	Only P values for most endpoints available. We wrote to study authors
Other bias	Low risk	No other sources of bias identified

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Breusov 2014.

Methods	Study design: Parallel‐group randomised trial Study dates: study dates not available Setting: outpatient, multicentre, national Country: Russia
Participants	Inclusion criteria: diagnosis of CP/CPPS (type IIIb), sexual dysfunction symptoms as defined by a locally‐developed questionnaire Exclusion criteria: diabetes mellitus, arterial hypertension (stage 1 or 2), postoperative and post‐traumatic sexual dysfunction Sample size: 57 participants were enrolled and randomised Age (years): Group 1 not available; Group 2 not available NIH‐CPSI baseline score: Group 1 mean = 22.4; Group 2 mean = 21.6 All participants were men
Interventions	Group 1 (n = 29): Prolit Super, 2 capsules at breakfast and lunchtime orally for 2 months, containing:a tablet of 600 mg strobilanthi folium, orthosiphonis folium, radix ginseng, sea horse, imperatae rhizoma, glycyrrhizae radix Group 2 (n = 28): placebo, 2 capsules at breakfast and lunchtime orally for 2 months Co‐interventions: no information available
Outcomes	Prostatitis Symptoms How measured: NIH‐total score and pain, urinary, and QoL domains Time points measured: baseline, 1 month, 2 months Time points reported: baseline, 1 month, 2 months Adverse event How measured: narratively
Funding sources	none
Declarations of interest	none
Notes	This article was written in Russian. No contact information available
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	No information available. Authors replied they used random numbers
Allocation concealment (selection bias)	Unclear risk	No information available. Authors did not provide further information
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	No information available. Authors replied that participants were blinded, no information regarding study personnel
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	No information available. Authors replied that participants were blinded
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: All 57 enrolled completed the trial follow‐up and had outcome data available
Selective reporting (reporting bias)	Unclear risk	No protocol available. The information on variation (SD/SE) of the outcomes was not reported but the authors provided them
Other bias	Low risk	No other sources of bias were detected

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Cai 2014.

Methods	Study design: Parallel‐group randomised trial Study dates: start date March 2012 ‐ end date October 2012 Setting: outpatient, single centre, national Country: Italy
Participants	Inclusion criteria: presence of symptoms of pelvic pain for at least 3 months during the 6 months before study entry, a score in the pain domain of the NIH‑CPSI (14) of > 7 and a negative 4‑glass result in the Meares‑Stamey test Exclusion criteria: Patients < 18 and > 65 years of age, affected by major concomitant diseases, with known anatomical abnormalities of the urinary tract or with evidence of other urological diseases, and with residual urine volume > 50 ml resulting from bladder outlet obstruction were excluded. Men with a reported allergy to pollen extract, who had recently (< 4 weeks) undergone oral or parenteral treatment or who were currently using prophylactic antibiotic drugs were also excluded. Additionally, all patients with a history of gastrointestinal bleeding or duodenal or gastric ulcers were excluded. All patients positive to tests for chlamydia trachomatis (Ct), ureaplasma urealyticum, neisseria gonorrhoeae, herpes viruses (HSV 1/2) and human papillomavirus (HPV) were also excluded Sample size: 87 men Age (years): Group 1 = 33.8 years (SD 6.78); Group 2 = 33.7 (SD 5.44) Baseline NIH‐CPSI score: Group 1 = 24.9 (SD 2.1); Group 2 = 25.5 (SD 3.0) All participants were men
Interventions	Group 1 (n = 41): DEPROX 500® (1 g pollen extract, 500 mg per tablet, and vitamins B1, B2, B6, B9, B12 and PP; 2 capsules in the evening every 24 hours) for 4 weeks Group 2 (n = 46): ibuprofen (600 mg, 1 tablet 3 times a day) for 4 weeks Co‐interventions: no information
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: 30 days Time points reported: 30 days Urinary Symptoms How measured: IPSS score Time points measured: 30 days Time points reported: 30 days Quality of life How measured: QoL Italian score Time points measured: 30 days Time points reported: 30 days Adverse events How measured: Narrative account
Funding sources	Not available
Declarations of interest	Not available
Notes	E‑mail: ktommy@libero.it
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “single sequence of random assignments (simple randomization) was performed using a pseudo‑random number generator software”
Allocation concealment (selection bias)	Unclear risk	No information on allocation concealment. We wrote to study authors.
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Quote: “this was not a blinded study”
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Quote: “this was not a blinded study”
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: missing data for 1/41 and 2/46 participants in each study arm due to lost to follow‐up
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias detected

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Cai 2017.

Methods	Study design: Parallel‐group randomised trial Study dates: start date January 2015 ‐ end date December 2015 Setting: Outpatient ‐ single centre ‐ national Country: Italy
Participants	Inclusion criteria: Men aged 18 ‐ 65 years old with the presence of pelvic pain symptoms for at least 3 months during the 6 months before study enrolment in accordance with the EUA guidelines, a score in the pain domain of the NIH‐CPSI of > 4 and a negative result for the Meares‐Stamey 4‐glass test Exclusion criteria: individuals affected by major concomitant diseases or with known anatomical abnormalities of the urinary tract or with evidence of other urological diseases with residual urine volume > 50 mL resulting from bladder outlet obstruction; men with a reported allergy to pollen extract who had undergone oral or parenteral treatment or who were currently using prophylactic antibiotic drugs (in the last 4 weeks), and all patients who tested positive for sexual transmitted diseases Sample size: 70 participants randomised Age (years): Group 1 = 32.4 (SD 4.3); Group 2 = 32.8 (SD 4.9) NIH‐CPSI baseline score: Group 1 = 25.1 (SD 2.1); Group 2 = 25.6 (SD 2.9) All participants were men
Interventions	Group 1 (n = 36): 2 tables of pollen extract and vitamins in a single dose in the evening. Each tablet contained 1 g of pollen extract and vitamins B1, B2, B6, B9, B12, and PP. Duration: 3 months Group 2 (n = 34): 2 tables of bromelain in a single daily dose in the evening (extract obtained from the stem and fruit of the pineapple plant) Duration: 3 months. Co‐interventions: not available
Outcomes	Prostatitis symptoms How measured: NIH‐CPSI score and pain subscore Time points measured: baseline and 3 months Time points reported: baseline and 3 months Quality of life How measured: SF‐36 Time points measured: baseline and 3 months Time points reported: baseline and 3 months Quality of life How measured: Narrative
Funding sources	Not available
Declarations of interest	Quote: “No potential conflict of interest relevant to this article was reported.”
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “All patients who met the inclusion criteria were randomized to either the treatment or control group by using a computer‐generated allocation sequence”
Allocation concealment (selection bias)	Unclear risk	No information available
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Quote: “Neither the physicians nor the patients were blinded to the treatment type.”
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Quote: “Neither the physicians nor the patients were blinded to the treatment type.”
Incomplete outcome data (attrition bias)   All outcomes	High risk	All outcomes: outcome data were available for 32/36 participants in the pollen extract group and 33/34 in the bromelain group. Unbalanced attrition
Selective reporting (reporting bias)	Unclear risk	Protocol not available
Other bias	Low risk	No other sources of bias were identified

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Cavallini 2001.

Methods	Study design: Parallel‐group randomised trial Study dates: study dates not available Setting: outpatient ‐ single centre ‐ national Country: Italy
Participants	Inclusion criteria: individuals with a diagnosis of chronic abacterial prostatitis/prostatodynia (after anamnesis, physical examination, prostatic ultrasound, urinalysis and urine culture, sperm analysis and culture, urethral swab, Stamey test and antibiogram) Exclusion criteria: none specified Sample size: 54 men Age (years): median 34 (range 28 ‐ 44) Baseline NIH‐CPSI score: not available. All participants were men
Interventions	Group 1 (n = 22): mepartricin 40 mg per day during 60 days Group 2 (n = 20): vitamin C 500 mg per day during 60 days used as placebo Co‐interventions: not described
Outcomes	Adverse events Narratively
Funding sources	Not available
Declarations of interest	Not available
Notes	This study also measured spontaneous pain, palpatory pain, urinary frequency, nycturia and prostatic volume. Contact information not available
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available
Allocation concealment (selection bias)	Unclear risk	No information available
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	No blinding was mentioned. It is not clear that the placebo pills were similar to the experimental treatment
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	No blinding was mentioned. It is not clear that the placebo pills were similar to the experimental treatment
Incomplete outcome data (attrition bias)   All outcomes	High risk	All outcomes: 54 participants were randomised, 12 were lost to follow‐up (no reasons were reported for missing outcome data)
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias identified

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Cha 2009.

Methods	Study design: Parallel randomised trial Study dates: start date July 2006 ‐ end date March 2008 Setting: Outpatient ‐ single centre ‐ national Country: South Korea
Participants	Inclusion criteria: men aged ≥ 20 and ≤ 50 years old with symptoms of discomfort or pain in the pelvic region for at least a 3‐month period Participants had a clinical diagnosis of CP/CPPS (III) Exclusion criteria: men with previous history of CP/CPPS, BPH, or neurogenic bladder. Men with a prostate volume > 30 g at digital rectal examination or positive culture in urine or EPS. Men with suspected prostate cancer Total number of participants randomly assigned: 103 Age (mean, SD): Group 1 = 39.70 ± 7.72; Group 2 = 38.46 ± 7.52; Group 3 = 39.64 ± 9.62 Baseline NIH‐CPSI score: Group 1 = 24.6 (SD 6.9); Group 2 = 24.3 (SD 8.3); Group 3 = 24.7 (SD 7.4) All participants were men
Interventions	Group 1 (n = 36): Only co‐intervention ‐ 8 weeks Group 2 (n = 33): alfuzosin 10 mg daily for 8 weeks Group 3 (n = 34): terpene mixture (Rowatinex^®) 1 capsule 3 times a day for 8 weeks Co‐interventions: all participants received levofloxacin 100 mg 3 times a day for 8 weeks.
Outcomes	Prostatitis Symptoms How measured: NIH CPSI questionnaire Time points measured: baseline, 8 weeks after treatment Time points reported: baseline, 8 weeks after treatment Subgroups: no
Funding sources	Not reported
Declarations of interest	Not reported
Notes	Language of publication: Korean Young Jin Seo. E‐mail: seoyjin@korea.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. Wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. Wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	No information available. Wrote to study authors
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	No information available. Wrote to study authors
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	No information available. Wrote to study authors
Selective reporting (reporting bias)	Unclear risk	Protocol not available.
Other bias	Low risk	No other sources of bias detected.

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Cheah 2003.

Methods	Study design: Parallel‐group randomised trial Study dates: start date April 2000 ‐ end date September 2001 Setting: outpatient, multicentre, international Country: Malaysia and USA
Participants	Inclusion criteria: men aged 20 to 50 years old with diagnostic criteria for CP/CPPS with a score of 1 or more in the items pelvic pain and quality of life and 4 or more in item 9 of the NIH‐CPSI score, suffering from symptoms lasting more than 3 months and desired to be treated Exclusion criteria: criteria for bacterial infection of the prostate and urinary tract, significant medical problems, concurrent medication that could affect the lower urinary tract function and previous experience with alpha blockers; along with other exclusion criteria in a previous consensus Sample size: 100 randomised Age (years): Group 1 median 36 (range 24 ‐ 49); Group 2 median 35 (range 20 ‐ 50) NIH‐CPSI baseline score: Group 1 = 25.1 (SD 7.1); Group 2 = 27.2 (SD 7.7) All participants were men
Interventions	Group 1 (n = 50): Terazosin 1 mg for 4 days, 2 mg during 10 days and then 5 mg during 12 weeks Group 2 (n = 50): Placebo of similar appearance in the same dosage Co‐interventions: They were not permitted to take any other medication for CP/CPPS or those that affected the lower urinary tract
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline, week 2, 6 and 14 Time points reported: baseline, week 2, 6 and 14 Urinary Symptoms How measured: IPSS Time points measured: baseline, week 2, 6 and 14 Time points reported: baseline, week 2, 6 and 14 Adverse events How measured: Narratively
Funding sources	Supported by an unrestricted grant from Abbott Laboratories, Malaysia
Declarations of interest	The contact author has "financial interest and/or other relationship with Abbott Laboratories"
Notes	Contact information: Department of Urological Surgery, University of Washington School of Medicine, VA Puget Sound Health Care System, 1660 S. Columbian Way, Seattle, Washington 98108
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “Random number table”
Allocation concealment (selection bias)	Unclear risk	No information available.
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	Double‐blind study. Blinding of personnel not described. Participants were blinded
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Participants were blinded using placebo
Incomplete outcome data (attrition bias)   All outcomes	High risk	All outcomes: 14% of participant in each group did not complete assessments
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias detected

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Chen 2009.

Methods	Study design: Parallel‐group randomised trial Study dates: start date October 2007 ‐ end date August 2008 Setting: Outpatient ‐ single centre ‐ national Country: China
Participants	Inclusion criteria: Individuals aged 20 to 50 years old, who meet the diagnostic criteria for type IIIB chronic prostatitis, with a course of disease 3 months to 4 years and had a NIH‐CPSI scoring of 10 or more. Individuals who did not take medications for chronic prostatitis or urination in the past week and who met the criteria of “chi and blood stasis syndrome” based on Traditional Chinese Medicine (TCM) theory of syndrome differentiation Exclusion criteria: Individuals with positive results of expressed prostate massage culture; individuals with pain and discomfort caused by other diseases; individuals with serious liver or kidney insufficiency and those who were allergic to the drugs used in this trial Sample size: 70 patients Age (years): Group 1 not available; Group 2 not available; Overall 20 ˜ 45, mean = 29.6 NIH‐CPSI baseline score: Group 1 = 25.3 (SD 3.8); Group 2 = 24.1 (SD 3.4) All participants were men
Interventions	Group 1 (n = 36): Qiantongding decoction (oral) twice a day for 1 month Group 2 (n = 34): XiaoYanTong (oral) 25 mg three times a day for 1 month Co‐interventions: All other medications and treatment options were discontinued during the process
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI (total, pain, quality of life) Time points measured: pre‐treatment, post‐treatment Time points reported: pre‐treatment, post‐treatment Adverse Events How measured: Narratively
Funding sources	Not mentioned
Declarations of interest	Not mentioned
Notes	This study was written in Chinese. Email: cdn0125@126.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “Patients were assigned to trial group (36 patients) and control group (34 patients) by simple random sampling” (p 90). Comment: However, it is unclear what the exact method was and how the allocation process was carried out. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	Allocation concealment was not described. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Masking of participants and personnel was not described. However, considering the visible difference between the 2 drugs, one could tell which medication the participants was taking. Therefore, masking was unlikely
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Blinding was unlikely (visibly different interventions)
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data were available for all participants
Selective reporting (reporting bias)	Unclear risk	No protocol available. We wrote to study authors
Other bias	Low risk	No other sources of bias identified

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Chen 2011.

Methods	Study design: Parallel‐group randomised trial Study dates: start date July 2003 ‐ end date March 2007 Setting: outpatient ‐ national ‐ single centre Country: China
Participants	Inclusion criteria: Patients were included if they had pain or discomfort in the pelvic region for at least 3 months, a total score of at least 12 on the NIH‐CPSI and anticipated improvement of symptoms with therapy Exclusion criteria: Participants with previous treatment with tamsulosin or any other alpha‐adrenergic receptor blocker for any reason, participants with chronic bacterial prostatitis, previous urinary tract infection within the last year, history of genitourinary cancer, inflammatory bowel disease, urethral stricture, symptomatic genital herpes, neurologic disease affecting the bladder, those who were taking medication that could affect lower urinary tract function, and those with benign prostatic hyperplasia or elevated PSA and those with severe symptoms (total NIH‐CPSI score > 38) Sample size: 100 randomised Age (years)(mean +/‐ SD): Group 1 tamsulosin (35.3 ± 6.8); Group 2 placebo (33.3 ± 7.2) Baseline NIH‐CPSI score: Group 1 = 23.3 (SD 6.2); Group 2 = 22.5 (SD 5.6) All participants were men
Interventions	Group 1 (n = 50): 0.2 mg of tamsulosin once daily for 6 months Group 2 (n = 50): identical‐looking placebo Co‐interventions: All participants were instructed to avoid spicy food, caffeine and alcohol during the study period
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI total score Time points measured: at the start of treatment (baseline) and at 3, 6, 12, 18 and 30 months after initiation of treatment Time points reported: at the start of treatment (baseline) and at 3, 6, 12, 18 and 30 months after initiation of treatment Sexual Dysfunction How measured: IIEF score Time points measured: at the start of treatment (baseline) and at 3, 6, 12, 18 and 30 months after initiation of treatment Time points reported: at the start of treatment (baseline) and at 3, 6, 12, 18 and 30 months after initiation of treatment Adverse events How measured: Narratively
Funding sources	No information available
Declarations of interest	Quote: “None.”
Notes	Contact information: cy0324@yahoo.com.cn
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “Patients were randomly allocated using computer‐generated random numbers into two equal groups”
Allocation concealment (selection bias)	Unclear risk	No information available. We wrote to study authors (email bounced)
Blinding of participants and personnel (performance bias)   Subjective outcomes	Low risk	Quote: “Study investigators and subjects were unaware of the treatment assignments.”
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Quote: “Study investigators and subjects were unaware of the treatment assignments.”
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes at 6 months: outcome data were available in 46/50 in the tamsulosin group and 47/50 in the placebo group (low risk) All outcomes at 12 months: outcome data were available in 45/50 in the tamsulosin group and 47/50 in the placebo group (low risk) All outcomes at 30 months: outcome data were available in 35/50 in the tamsulosin group and 37/50 in the placebo group (high risk)
Selective reporting (reporting bias)	Unclear risk	No protocol available. We wrote to study authors (email bounced)
Other bias	Low risk	No other sources of bias were identified

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Cheng 2010.

Methods	Study design: Parallel‐group randomised trial Study dates: not available Setting: outpatient – single centre ‐ national Country: Taiwan
Participants	Inclusion criteria: men with chronic non‐bacterial prostatitis Exclusion criteria: not available Sample size: 215 men Age (years): not available Baseline NIH‐CPSI score: not available All participants were men
Interventions	Group 1 (n = 51): levofloxacin 500 mg daily for 6 weeks Group 2 (n = 53): ciprofloxacin 250 mg twice daily for 6 weeks Group 3 (n = 61): levofloxacin 500 mg twice daily for 6 weeks Group 1 (n = 50): control group Co‐interventions: Not available
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline, 3 and 6 weeks Time points reported: not available Co‐interventions: NSAIDs (diclofenac 500mg) twice daily and alpha blocker (tamsulosin 0.2 mg) twice daily were prescribed for all participants
Funding sources	Not available
Declarations of interest	Not available
Notes	This information was provided by two abstracts, no full text was available. No contact information available
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available (abstract only)
Allocation concealment (selection bias)	Unclear risk	No information available (abstract only)
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	No information available (abstract only)
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	No information available (abstract only)
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	No information available (abstract only)
Selective reporting (reporting bias)	Unclear risk	No information available (abstract only)
Other bias	Unclear risk	No information available (abstract only)

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Choe 2014.

Methods	Study design: Parallel‐group randomised trial Study dates: start date January 2011 ‐ end date December 2011 Setting: Outpatient ‐ multicentre ‐ national Country: Republic of Korea
Participants	Inclusion criteria. Participants with a diagnosis of category IIIa of IIIb chronic prostatitis and a NIH‐CPSI score ≥ 15 Exclusion criteria: The presence of urinary tract infection or uropathogen within the past 12 months, serious medical problems, NIH consensus exclusion criteria (Alexander 2004a), drug therapy that might affect lower urinary tract functions within the past 3 months Sample size: 75 participants Baseline NIH‐CPSI score: Group 1 = 20.5; Group 2 = 21.2; Group 3 = 22.5 Age (years): range 22 ‐ 42 years, mean = 29.1 ± 5.2 years All participants were men
Interventions	Group 1 (n = 25) received 500 mg ciprofloxacin twice a day for 4 weeks Group 2 (n = 25) received 100 mg aceclofenac twice a day for 4 weeks Group 3 (n = 25) received 150 mg roxithromycin twice a day for 4 weeks Co‐intervention: none
Outcomes	Prostatitis symptoms How measured: NIH‐CPSI score and subscore Time points measured: baseline, 4, and 12 weeks after drug administration Time points reported: baseline, 4, and 12 weeks after drug administration. Some results were presented graphically Adverse events How measured: Narratively Urinary symptoms How measured: 7‐item International Prostate Symptom Score (IPSS) Comment: presumably only total IPSS score without QoL score Time points measured: baseline, 4, and 12 weeks after drug administration Time points reported: not reported
Funding sources	Not available
Declarations of interest	None
Notes	ClinicalTrials.gov Identifier: NCT01843946 Email: lee.seungju@gmail.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "To prevent the imbalance of subject number among the groups, which could occur upon general randomization, blocked randomization was used in this study. In addition, after the randomization table was prepared for each study center, the subjects were randomized to the treatment groups according to the randomization table.” Comment: Probably done
Allocation concealment (selection bias)	High risk	Randomisation table, “open‐label, randomized allocation”
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Open‐label study
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Open‐label study
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	No information available
Selective reporting (reporting bias)	High risk	The table of IPSS scores outlined in absolute numbers is missing. Instead, the authors provided the results of IPSS score change in the Results section NIH‐CPSI score do not include variability (SD or IQ range), some time points are presented graphically
Other bias	Low risk	No other sources of bias were identified

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Churakov 2012.

Methods	Study design: Parallel‐group randomised trial Study dates: study dates not available Setting: outpatient, single centre, national Country: Russia
Participants	Inclusion criteria: age 22 ‐ 60; diagnosis of abacterial CP/CPPS, erectile dysfunction symptoms Exclusion criteria: the following co‐morbidities: non‐compensated forms of endocrine, cardiovascular, and mental disorders; prostate cancer, prostate hyperplasia Sample size: 60 participants were enrolled and randomised Age (years): Group 1 (not available); Group 2 (not available) NIH‐CPSI baseline score: not available All participants were men
Interventions	Group 1 (n = 30): Cytoflavin 10 ml intravenously for 10 days, then 2 pills of Cytoflavin twice a day for 20 days Group 2 (n = 30): no treatment Co‐intervention: α‐blockers ‐ 1 month, nonspecific anti‐inflammatory drugs – 2 weeks, prostate massage and vibrovacuum fallostimulation – 10 times, antibiotics – 10 days
Outcomes	None of the outcomes relevant for this review (See Notes)
Funding sources	none
Declarations of interest	none
Notes	Prostatitis symptoms were reported using a locally‐ developed scale; we have no information regarding its validation. Email: vrachp@mail.ru
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available
Allocation concealment (selection bias)	Unclear risk	No information available
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	No information available
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	No information available
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	No information available
Selective reporting (reporting bias)	High risk	No protocol available. The information on variation (SD/SE) of the outcomes was reported
Other bias	Low risk	No other sources of bias were identified

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De Rose 2004.

Methods	Study design: Parallel‐group randomised trial Study dates: start date June 2001 ‐ end date November 2002 Setting: outpatient ‐ single centre ‐ national Country: Italy
Participants	Inclusion criteria: men aged 18 ‐ 55 years with nonbacterial type III CP/CPPS for at least 1 year; suffering from pain, sexual dysfunction and difficulty voiding Exclusion criteria: evidence of infection in urethral swab, urine culture and semen culture in the participant and sexual partner, PSA > 4 ng/mL; HIV infection, diabetes mellitus, and stroke in the last 3 months. Participants had not taken antibiotics in the last 3 months Sample size: 30 randomised and 4 were excluded after randomisation Age (years): Group 1 median 32 (range 26 ‐ 49); Group 2 median 34 (range 26 ‐ 52) NIH‐CPSI baseline score: Group 1 median 25 (range 21 ‐ 34); Group 2 median 25 (range 18 ‐ 45) All participants were men
Interventions	Group 1 (n = 13): mepartricin 40 mg daily for 60 days Group 2 (n = 13): placebo daily for 60 days Co‐interventions: not described
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline and 60 days Time points reported: baseline and 60 days Adverse events How measured: Narratively
Funding sources	Not available
Declarations of interest	Not available
Notes	No email address available. Contact information: Aldo Franco De Rose, M.D., “Luciano Giuliani”  Urology Department, University of Genoa, Via Donato Somma 77/9, Genova 16167, Italy
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “The 30 envelopes were sealed, mixed, and numbered in progressive order before being placed in a box” – random sorting.
Allocation concealment (selection bias)	Low risk	Quote: “Randomization was performed using 30 opaque envelopes”
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	Not specified whether personnel were blinded
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Placebo was used for the blinding of participants
Incomplete outcome data (attrition bias)   All outcomes	High risk	All outcomes: 4 participants (2/15 in each study arm) were excluded after randomisation for the presence of positive cultures
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias were identified

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Dunzendorfer 1983.

Methods	Study design: Parallel‐group randomised trial Study dates: Not available Setting: Outpatient, single centre, national Country: Germany
Participants	Inclusion criteria: individuals with more than 12 months of diagnosis of chronic abacterial prostatitis with negative urine and sperm culture who were refractory to other treatments Exclusion criteria: not available Sample size: 40 NIH‐CPSI score: not available Age (years): Overall median 39 years old (range 21 ‐ 56) All participants were men
Interventions	Group 1 (n = 20): phenoxybenzamine 10 mg twice daily for 6 weeks Group 2 (n = 20): placebo Co‐interventions: not available
Outcomes	Adverse events How measured: Narratively
Funding sources	Röhm Pharma GmbH, Weiterstadt
Declarations of interest	Not available
Notes	Email: not available
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Block‐randomisation, assumed random.
Allocation concealment (selection bias)	Unclear risk	No information available.
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	Double‐blind, not specified who was blinded.
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	Double‐blind, not specified who was blinded.
Incomplete outcome data (attrition bias)   All outcomes	High risk	Outcome data was available for 17/20 patients in the intervention arm, and 13/20 in the placebo arm.
Selective reporting (reporting bias)	Unclear risk	Protocol not available.
Other bias	Low risk	No other sources of bias identified.

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Elist 2006.

Methods	Study design: Parallel‐group randomised trial Study dates: study dates not available Setting: outpatient ‐ national ‐ single centre Country: USA
Participants	Inclusion criteria: men aged 20 to 60 years old with a diagnosis of CP/CPPS type III prostatitis with no response to previous treatment Exclusion criteria: positive semen, prostatic fluid or urine culture; elevated PSA, abnormalities in cystoscopy or ultrasonography, abnormal cystometrography, benign prostatic hyperplasia with an AUA score exceeding 15, bladder neck obstruction, abnormal uroflowmetry results, > 3 to 5 red blood cells in urine sample Sample size: 60 randomised Age (years): overall mean 35 years (range 20 ‐ 55) NIH‐CPSI baseline score: not available All participants were men
Interventions	Group 1 (n = 30): Prostat/Poltit containing “74 mg highly defined extract of pollen from selected Graminae species” during 6 months Group 2 (n = 30): Identical‐looking Placebo during 6 months Co‐interventions: the participants were told not to engage in other pharmacological and non‐pharmacological treatments
Outcomes	Adverse events Narratively
Funding sources	Quote: “The study medication was produced by Allergon AB”
Declarations of interest	Not available
Notes	The clinical outcome measure was a non‐validated symptom score. Email: drelist@gmail.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Using computer‐generated sequence
Allocation concealment (selection bias)	Low risk	Pharmacy central allocation
Blinding of participants and personnel (performance bias)   Subjective outcomes	Low risk	Participants and personnel were blinded to the treatment arm
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Quote: “The placebo tablets were identical in appearance to the active tablets but contained no pollen extract”
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: 2 participants (7%) were lost to follow‐up in the placebo group with no outcome data
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias were detected

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Elshawaf 2009.

Methods	Study design: Parallel‐group randomised trial Study dates: not available Setting: outpatient ‐ single centre ‐ national Country: Egypt
Participants	Inclusion criteria: clinically‐proven chronic prostatitis and chronic pelvic pain syndrome type III after failure of several courses of medical therapy were selected from patients referred to the neuro‐urology unit of the urology department for voiding dysfunction evaluation and management; “with urodynamically proven detrusor external sphincter dyssynergia (DESD)” Exclusion criteria: not available Sample size: 52 men Age (years): overall range 25 to 48 years Baseline NIH‐CPSI score: not available All participants were men
Interventions	Group 1 (n = 26): Received 100 units of reconstituted Botulinum Toxin A (BTA) into the external urethral sphincter (EUS) endoscopically Group 2 (n = 26): Received combined injection in the EUS and prostate with 100 units of BTA for each location Co‐interventions: none
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline, 12 weeks, 6 and 12 months Time points reported: Not available (only P value) Adverse Events How measured: Narratively
Funding sources	Not available
Declarations of interest	Not available
Notes	This trial was only available as an abstract. We attempted contact with study author: ishamshawaf@gmail.com, h_shawaf2005@yahoo.com Quote: “55 % of GI [Group 1] patients were scheduled for second session of combined chemo‐denervation following the same protocol for GII at the end of the study period.”
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Abstract only. No information available
Allocation concealment (selection bias)	Unclear risk	Abstract only. No information available
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	Abstract only. No information available
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	Abstract only. No information available
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Abstract only. No information available
Selective reporting (reporting bias)	Unclear risk	Abstract only. No information available
Other bias	Unclear risk	Abstract only. No information available

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Erdemir 2010.

Methods	Study design: Parallel‐group randomised trial Study dates: start date January 2004 ‐ end date December 2008 Setting: outpatient ‐ single centre ‐ national Country: Turkey
Participants	Inclusion criteria: Type III chronic prostatitis Exclusion criteria: Neurologic diseases, urethral strictures, chronic diseases such chronic liver and kidney failure and diabetes mellitus, history of pelvic surgery, chronic antidepressant, anti‐psychotic and anxiolytic drug use with prior psychiatric disorder diagnosis and recent urinary tract infections Sample size: 87 Age (years): Group 1: 34.13 ± 7.39; Group 2: 34.76 ± 7.99; Group 3: 33.72 ± 8.25 Baseline NIH‐CPSI score: Group 1: 23.92 ± 5.3; Group 2: 24.11 ± 4.2; Group 3: 23.72 ± 3.2 All participants were men
Interventions	Group 1 (n = 45): A quinolone 500 mg 4 ‐ 6 weeks + ibuprofen 400 mg 4 weeks + terazosin 5 mg 12 weeks. Possibly oral, once a day Group 2 (n = 17): Terazosin 5 mg 12 weeks. Possibly oral, once a day Group 3 (n = 25): A quinolone 500 mg 4 ‐ 6 weeks + ibuprofen 400 mg 4 weeks. Possibly oral, once a day Co‐interventions: None
Outcomes	Prostatitis symptoms How measured: NIH‐CPSI score (subscores) Time points measured: Not reported Time points reported: Only mean follow‐up times reported Group 1: 7.13 ± 2.51 months Group 2: 6.01 ± 1.52 months Group 3: 6.93 ± 2.12 months Subgroups: None
Funding sources	Not reported
Declarations of interest	Not reported
Notes	"Improvement" was reported but this outcome was not defined in the report E‐mail: ffrat60@yahoo.com, ffrat60@gmail.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available
Allocation concealment (selection bias)	Unclear risk	No information available
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Open‐label study
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Open‐label study
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data were available for all participants
Selective reporting (reporting bias)	High risk	Only subscores were reported, not total NIH‐CPSI score
Other bias	Low risk	No other sources of bias were identified

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Falahatkar 2015.

Methods	Study design: Parallel‐group randomised trial Study dates: start date November 2011 ‐ end date January 2013 Setting: outpatient ‐ single centre ‐ national Country: Iran
Participants	Inclusion criteria: men aged ≥ 18 years old with type III CP/CPPS, refractory to a 4‐ to 6‐week treatment with antibiotics, alpha blockers and muscle relaxants; with a pain and urinary score ≥10 and a pain score ≥8 using the NIH‐CPSI score Exclusion criteria: “previous or concurrent malignancy; inflammatory bowel disease; history of pelvic radiation and systemic or intravesical chemotherapy; previous pelvic and rectal surgery or trauma; presence of a neurological disorder affecting the bladder; bladder stones; urethral stricture; history of prostate surgery or biopsy; urinary tract infection or sexually transmitted disease in the last 3 months; neuromuscular junction disorder; consumption of anticongestives, anticholinergics or any medicine affecting the neuromuscular junction in the last 2 weeks; coagulopathy; intake of antiplatelet agents in the last 10 – 14 days, anticoagulants in the last 7 days or steroids or sex hormones in the last 4 months; opioid or drug or alcohol abuse during the last 5 years; serum PSA level > age‐specific range; abnormal digital rectal examination with family history of prostate cancer; serum creatinine > 2 mg/dl; abnormal urinary cytology with haematuria; post‐voiding urine residue > 200 mL; indwelling urinary catheter, cystostomy or nephrostomy; penile prosthesis or artificial urinary sphincter; previous injection of or hypersensitivity to botulinum toxin A" Sample size: 60 Age (years): Group 1 mean 42.67 (SD 11.24); Group 2 mean 38.17 (SD 11.77) Baseline NIH‐CPSI score: Group 1 = 34.97 (SD 4.81); Group 2 = 33.20 (SD 5.19) All participants were men
Interventions	Group 1 (n = 30): 100 IU of Botulinum Toxin A (BTA) was diluted in 2 ml of normal saline and administrated for prostate volumes < 30 mL. For volumes 30 ‐ 60 ml, 200 UI were used Group 2 (n = 30): Placebo injections of 2 mL of normal saline injections Co‐interventions: all participants received 10 mL of lidocaine gel (2%) into the urethra 10 minutes before injections at 3 different sites of each lateral lobe, using a 23‐gauge endoscopic needle and rigid cystoscopy. A 16‐F Foley catheter was fixed for 12 hours after injection and oral ciprofloxacin 500 mg twice a day was administered for 7 days. All medications for CP/CPPS were discontinued from 1 month
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline, 1, 3 and 6 months Time points reported: baseline, 1, 3 and 6 months Urinary Symptoms How measured: AUA‐symptom score Time points measured: baseline, 1, 3 and 6 months Time points reported: baseline, 1, 3 and 6 months Adverse events How measured: Narratively
Funding sources	“not available”
Declarations of interest	None declared
Notes	Clinical Trial registry:IRCT201208051853N8 Contact information: shah3000us@yahoo.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “In a 1:1 randomization schedule, the patients were divided into two equal groups:” Comment: Unclear how the random sequence generation was generated
Allocation concealment (selection bias)	Low risk	Quote: "Concealed numbered envelopes were used for group assignment, which were opened after gathering the baseline values." Comment: Low risk of bias for allocation concealment
Blinding of participants and personnel (performance bias)   Subjective outcomes	Low risk	Quote: “One examiner, blinded to the randomization schedule and treatment arrangement, evaluated all patients at baseline and follow‐up visits.” Comment: Patients were blinded with the use of placebo
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Quote: “One examiner, blinded to the randomization schedule and treatment arrangement, evaluated all patients at baseline and follow‐up visits.” Comment: Patients were blinded with the use of placebo
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: “All patients completed the follow‐up program and we had no missing data.”
Selective reporting (reporting bias)	Low risk	All outcomes matched those in the clinical trial registry
Other bias	Low risk	No other sources of bias were identified

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Giammusso 2017.

Methods	Study design: Parallel‐group randomised trial Study dates: start date June 2014 ‐ end date January 2015 Setting: outpatient ‐ single centre ‐ national Country: Italy
Participants	Inclusion criteria: men aged 22 to 61 years with complaints of chronic pelvic pain for at least 6 months; IPSS score > 13 at visit 1; pain domain of NIH‐CPSI higher than 1 at visit 1; total PSA lower than 4 ng/ml; with symptoms compatible with category III CP/CPPS according to the NIH criteria Exclusion criteria: men affected by major comorbidities, with known anatomical abnormalities of the urinary tract or with evidence of other urological diseases, and with residual urine volume > 50 ml resulting from bladder outlet obstruction; reported allergy to the drugs administered during the trial, who had recently undergone oral or parenteral treatment or who were currently using prophylactic antibiotic drugs or finasteride, or both; men with positive tests for sexually transmitted diseases Sample size: 44 participants Age (years): Overall mean 41.32 (SD 1.69) NIH‐CPSI baseline score: Not available All participants were men
Interventions	Group 1 (n = 22): Palmitoylethanolamide 300 mg plus alpha‐lipoic acid 300 mg (Peanase®), 2 capsules daily for 12 weeks Group 2 (n = 22): Serenoa repens at 320 mg, 1 capsule daily for 12 weeks Co‐interventions: "At time‐point V2 (visit two), after complete clinical and microbiological assessments, patients received a full course of pharmacological therapy." (prior to the experimental drug administration)
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline and 12 weeks Time points reported: baseline and 12 weeks (graphically) Urinary Symptoms How measured: IPSS Time points measured: baseline and 12 weeks Time points reported: baseline and 12 weeks (graphically) Sexual Dysfunction How measured: IIEF5 Time points measured: baseline and 12 weeks Time points reported: baseline and 12 weeks (graphically) Adverse Events How measured: Narrative
Funding sources	Not available
Declarations of interest	“No conflict of interest declared”
Notes	We contacted the study author for the missing information: bgiammusso@hotmail.it
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. We contacted study authors
Allocation concealment (selection bias)	Unclear risk	No information available. We contacted study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Single‐blind trial, it was not specified who was blinded. We contacted study authors
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	Single‐blind trial, it was not specified who was blinded. We have no information regarding participant blinding. We contacted study authors
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	All outcomes: follow‐up data are not available. We contacted study authors
Selective reporting (reporting bias)	High risk	No protocol available, outcome data were only presented graphically. We contacted study authors
Other bias	Unclear risk	Baseline data poorly reported (narrative fashion). We contacted study authors

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Giannantoni 2014.

Methods	Study design: Parallel‐group randomised trial Study dates: start date January 2009 ‐ end date December 2012 Setting: outpatient ‐ single centre ‐ national Country: Italy
Participants	Inclusion criteria: men >18 years old with pelvic or perineal pain, or both, and sexual dysfunction during at least 3 of the previous 6 months, with a score of at least 15 on the NIH‐CPSI Exclusion criteria: men with bacterial prostatitis, urethritis, urethral stricture, neurogenic bladder, those previously treated with antidepressants, with hepatic insufficiency, a history of alcohol use or evidence of chronic liver disease, and severe orthostatic hypotension Sample size: 38 Age (years): Group 1 mean 47 (SD 13); Group 2 mean 46.6 (SD 12.2) Baseline NIH‐CPSI score: Group 1 mean 25.1 (SD 3.7); Group 2 mean 24.25 (SD 8.4) All participants were men
Interventions	Group 1 (n = 20): oral duloxetine hydrochloride 60 mg/day. Duloxetine dose was escalated during the first 15 days. Duration of treatment: 16 weeks Group 2 (n = 18): only co‐interventions Co‐interventions: tamsulosin 0.4 mg/day, saw palmetto 320 mg/day during 16 weeks
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline and 16 weeks Time points reported: baseline and 16 weeks Sexual Dysfunction How measured: International Index of Erectile Function‐5 Time points measured: baseline and 16 weeks Time points reported: baseline and 16 weeks Anxiety and depression How measured: Hamilton Anxiety Rating Scale (HAM‐A) Time points measured: baseline and 16 weeks Time points reported: baseline and 16 weeks Anxiety and depression How measured: Hamilton Depression Rating Scale (HAM‐D) Time points measured: baseline and 16 weeks Time points reported: baseline and 16 weeks Adverse events How measured: Narratively
Funding sources	Not available
Declarations of interest	Not available
Notes	E‐mail: agianton@libero.it
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	The study reported “block randomization”, but there is no information about its sequence generation
Allocation concealment (selection bias)	Unclear risk	No information available
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	The study was not blinded (visibly different interventions)
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	The study was not blinded (visibly different interventions)
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Quote: “Four patients in group 1 stopped taking duloxetine due to intolerable adverse effects (nausea, sleep disturbances, sedation) within 1 month after the beginning of the study". Comment: It is unclear if all outcome measures include these participants (unbalanced attrition)
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias were identified

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Goldmeier 2005.

Methods	Study design: Parallel‐group randomised trial Study dates: study dates not available Setting: outpatient ‐ single centre ‐ national Country: UK
Participants	Inclusion criteria: men aged 18 to 60 with symptoms suggestive of CP/CPPS Exclusion criteria: chronic bacterial prostatitis (4‐glass test), those with a diagnosis of > 2 years, who had taken medication in the past 4 weeks, HIV positive, prostatic carcinoma, allergic to zafirlukast or doxycycline, renal or hepatic impairment, men with a poor command of English and those with known eosinophilia or severe allergic rhinitis Sample size: 20 men Age (years): Group 1 mean 36.4 (SD 13.9); Group 2 mean 35.1 (SD 9.5) Baseline NIH‐CPSI score: Not available All participants were men
Interventions	Group 1 (n = 10): Zafirlukast 20 mg twice a day for 4 weeks Group 2 (n = 7): Placebo tablets twice a day for 4 weeks Co‐interventions: doxycycline 100 mg twice daily for 4 weeks was administered to all participants
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score (subscores) Time points measured: baseline, 4 weeks Time points reported: baseline, 4 weeks Adverse events How measured: Narratively
Funding sources	The Prostate Research Campaign UK and AstraZeneca, UK
Declarations of interest	Not available
Notes	Total score was not available Email: david.goldmeie@st‐marys.nhs.uk
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	A randomisation list was used to create permuted blocks of different sizes
Allocation concealment (selection bias)	Low risk	Central allocation by pharmacy
Blinding of participants and personnel (performance bias)   Subjective outcomes	Low risk	The participants and personnel were blinded
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Participants were blinded
Incomplete outcome data (attrition bias)   All outcomes	High risk	All outcomes: 3/7 participants (30%) were lost at follow‐up (missing outcome data) in the placebo arm
Selective reporting (reporting bias)	Unclear risk	Protocol was not available. Total NIH‐CPSI score was not reported
Other bias	Low risk	No other sources of bias were identified

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Gottsch 2011.

Methods	Study design: Parallel‐group randomised trial Study dates: not available Setting: outpatient ‐ single centre ‐ national Country: USA
Participants	Inclusion criteria: Men aged 18 – 65 years with CPPS type IIIA or IIIB were identified from the prostatitis clinic; at least 15 in the NIH‐CPSI score; all men had extensive previous treatment Exclusion criteria: active urinary tract infection, genitourinary malignancy, suicidal or overtly psychotic behaviour, post‐surgical pain, pain from another source in the genito‐urinary tract (e.g. renal calculi), history of radiation therapy, or history of genitourinary tuberculosis Sample size: 29 randomised Age (years): Group 1 mean 47 (range 25 ‐ 77); Group 2 54 (range 25 ‐ 80) NIH‐CPSI baseline score: Group 1 = 27.4 (SD 5.5); Group 2 = 24.5 (SD 5.2) All participants were men
Interventions	Group 1 (n = 13): onabotulinum toxin A was injected after sterile preparation of the perineal skin: 100 U BTX‐A was diluted in 2 ml normal saline and the injection was guided using an electromyography needle to instil the preparation into the bulbospongiosus muscle and the mid‐bulbospongiosus muscle Group 2 (n = 16): saline injection using the same procedure Co‐interventions: not described
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline and at 1 and 2 months Time points reported: baseline, 1 and 2 months (for the cross‐over phase) Adverse events How measured: narratively
Funding sources	Not available
Declarations of interest	Reported as “none”
Notes	10 participants in the saline injection group switched to open‐label Botulinum toxin A injection and these results are the one presented at 2 months C. C. Yang. E‐mail: cyang@u.washington.edu
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	“Randomization took place via random number generation”
Allocation concealment (selection bias)	Low risk	“blinded packaging by the research pharmacy.”
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	No information provided about blinding. Participants in the placebo group chose Botulinum injection at 1 month and “Patients were noted to have decreased spasm of the perineal musculature following injection”
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	No information provided about blinding. Participants in the placebo group chose Botulinum injection at 1 month and “Patients were noted to have decreased spasm of the perineal musculature following injection”
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data was available for all participants.
Selective reporting (reporting bias)	Unclear risk	Protocol not available
Other bias	Low risk	No other bias detected

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Gül 2001.

Methods	Study design: parallel group randomised trial Study dates: start date May 1997 ‐ end date October 1999 Setting: outpatient, national, single centre Country: Turkey
Participants	Inclusion criteria: diagnosed with CPPS Exclusion criteria: not specified Sample size: 91 recruited, probably 89 randomised Age (years): mean 39.6 (overall range 17‐48) NIH‐CPSI baseline score (PSSI score): Group 1 9.61 (SD 1.61) Group 2 9.27 (SD 1.88) All participants were men
Interventions	Group 1 (n = 39): terazosin 2 mg daily for three months Group 2 (n = 30): placebo for three months Co‐interventions: preventive measures (frequent sexual intercourse, avoid spicy food and constipation)
Outcomes	Prostatitis Symptoms How measured: PSSI Time points measured: before and after the treatment Time points reported: before and after treatment Adverse events How measured: Narratively
Funding sources	Not available
Declarations of interest	Not available
Notes	Address for correspondence: Osman Gül, MD, Y. Ziraat Mahallesi 14. sokak No: 8/C (Ok‐Ya Tıp Merkezi), Dı¸skapı, Ankara, Turkey Phone: +90 312 342 34 94; Fax: +90 312 384 02 83 91 participants were recruited, but then the authors say that 42 and 47 (89 participants) were randomised in two groups. It is not stated the reason for the two missing participants.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available
Allocation concealment (selection bias)	Unclear risk	No information available
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	No information available
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	They used placebo tablets but there is not mention of blinding
Incomplete outcome data (attrition bias)   All outcomes	High risk	All outcomes: 8/47 (17.0%) in terazosin and 12/42 (28.6%) in placebo lost to follow‐up
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias identified

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Hu 2015.

Methods	Study design: parallel group randomised trial Study dates: start date August 2012 ‐ end date August 2013 Setting: single center in China, outpatient Country: China
Participants	Inclusion criteria: Men aged 18‐56. Prostatic fluid examination: Lecithin body disappear or decrease in number, normal or raised WBC count, normal urine test, and prostatic fluid culture negative. Discomfort during urination. NIH‐CPSI pain subscore >= 10. Men who had not taken alpha‐blockers, steroids, or antibiotics recently. Exclusion criteria: Men aged below 18 or above 56. Patients who had serious primary diseases of the liver, kidney, cerebral blood vessels, cardiovascular system, or hematopoietic system. Patients who had BPH, prostate cancer, or serious psychiatric disorders. Patients who were allergic to the drugs concerning the trial. Patients who did not take medications according to trial protocol or whose treatment effect could not be evaluated. Patients who did no meet inclusion criteria. Sample size: 96 patients randomized Age (years): Intervention group: range 24‐48. Mean ± SD: 32.4 ‐ 5.8 Control group: range 25‐46. Mean ± SD: 31.9 ‐ 5.5 NIH‐CPSI baseline score: Intervention group: 27.63 ± 9.52 Control group: 27.16 ± 9.36 Sex (M/F): All participants were men.
Interventions	Intervention group: bazheng decoction. 320mL daily (160mL in the morning and 160mL in the evening). The course of treatment was 7 days. Treatment effect was observed after 2 treatment courses. Control group: only the co‐intervention Co‐interventions:Tamsolusin 0.2mg daily
Outcomes	Prostatitis symptoms How measured: NIH‐CPSI score Time points measured: Baseline, week 2 Time points reported: Baseline, week 2 Subgroups:None. Adverse events Not reported.
Funding sources	Not available
Declarations of interest	Not available
Notes	A composite clinical and biochemical outcome (white blood cells) is reported to indicate “improvement”. No contact information available. This study was written in Chinese.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "(In Chinese) 96 patients were randomly allocated to control group (48 patients) and trial group (48 patients) using random number table method".
Allocation concealment (selection bias)	Unclear risk	No information available.
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Visibly different intervention, blinding was unlikely
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Visibly different intervention, blinding was unlikely
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data were available for all participants
Selective reporting (reporting bias)	Unclear risk	No protocol available.
Other bias	Low risk	No other sources of bias were detected

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Iwamura 2015.

Methods	Study design: Parallel‐group randomised trial Study dates: start date 2009 ‐ end date 2013 Setting: outpatient ‐ multicentre ‐ national Country: Japan
Participants	Inclusion criteria: criteria (Propert) men aged 20 ‐ 80 with symptoms of pelvic pain for 3 months or more before study, with a total NIH‐CPSI score ≥ 15 points Exclusion criteria: documented urinary tract infection, urethritis, epididymitis and sexually transmitted disease, prostate surgery, urogenital cancer, treatment with phytotherapeutic agents, alpha blockers and antimicrobials and the presence of bladder outlet obstruction Sample size: 100 randomised Age (years): Group 1 mean 50.1 (SD 13.7); Group 2 mean 53 (SD 14.6) Baseline NIH‐CPSI score: Group 1 mean 22.3 (SD 4.7); Group 2 mean 20.3 (SD 5.8) All participants were men
Interventions	Group 1 (n = 50): Eviprostat 2 capsules 3 times a day (umbellate wintergreen Chimaphila umbellate extract 0.5 mg, aspen Populus tremula extract 0.5 mg, small pasque flower Pulsatilla pratensis extract 0.5 mg, field horsetail Equisetum arvense extract 1.5 mg and germ oil from wheat Tritium aestivum 15.0 mg) for 8 weeks Group 2 (n = 50): pollen extract 2 capsules 3 times a day (60 mg Cernitin T60 and 3 mg Cernitin GBX) for 8 weeks Co‐interventions: none described
Outcomes	Prostatitis symptoms How measured: NIH‐CPSI score Time points measured: baseline, 4 and 8 weeks Time points reported: baseline, 4 and 8 weeks Adverse events How measured: Narratively
Funding sources	not available
Declarations of interest	Quote: “The authors declare that they have no competing interests.”
Notes	Clinical Trial record: UMIN000019618. We wrote to study authors to obtain information for 'Risk of bias' judgements and standard deviations for the primary outcome. We wrote to goodwin@cc.hirosaki‐u.ac.jp, but the email bounced. We calculated the SD from exact P values
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “The allocation manager randomly determined” Comment: Not enough information to make judgement. We wrote to study authors
Allocation concealment (selection bias)	Low risk	Allocation using sealed numbered envelopes
Blinding of participants and personnel (performance bias)   Subjective outcomes	Low risk	Double‐blind study – identical regimens
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Double‐blind study – identical regimens
Incomplete outcome data (attrition bias)   All outcomes	High risk	9/50 were excluded after randomisation in the Eviprostat group, 11/50 were excluded after randomisation in the Pollen Extract group
Selective reporting (reporting bias)	Low risk	Protocol was published (UMIN000019618) and review outcomes were well described
Other bias	Low risk	No other sources of bias identified

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Jeong 2008.

Methods	Study design: Parallel‐group randomised trial Study dates: start date January 2004 ‐ end date December 2004 Setting: outpatient ‐ single centre ‐ national Country: South Korea
Participants	Inclusion criteria: men with a diagnosis of type III CP/CPPS, aged 20 ‐ 60 years old with experience of pelvic pain for > 3 months during the previous 6 months Exclusion criteria: benign prostatic hyperplasia, NIH consensus criteria (Propert), urinary tract surgery or previous treatment Sample size: 81 randomised Age (years): Group 1 mean 37.5 (range 30 ‐ 50); Group 2 mean 41.5 (range 23 ‐ 56) Group 3 mean 41.1 (range 27 ‐ 60) Baseline NIH‐CPSI score: Group 1 mean 22.6; Group 2 mean 22.4; Group 3 mean 24.1 All participants were men
Interventions	Group 1 (n = 26): levofloxacin 100 mg twice daily for 6 weeks Group 2 (n = 26): doxazosin 4 mg once daily before sleep for 6 weeks Group 2 (n = 29): levofloxacin 100 mg twice daily plus doxazosin once daily for 6 weeks Co‐interventions: none described
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline and 6 weeks Time points reported: baseline and 6 weeks. No SD available (we wrote to study authors) Adverse events How measured: Narratively
Funding sources	Not available
Declarations of interest	Not available
Notes	Contact information: Dr. Hyeon Jeong (drjh@brm.co.kr)
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Visibly different intervention, blinding was unlikely
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Visibly different intervention, blinding was unlikely
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data were available for all participants
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias were detected

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Jiang 2009.

Methods	Study design: Parallel‐group randomised trial Study dates: start date October 2007 ‐ end date October 2008 Setting: outpatient ‐ single centre ‐ national Country: China
Participants	Inclusion criteria: individuals with pelvic pain for > 3 months, mostly in regions such as the perineum, penis, crissum, urethra, lumbosacral region, etc. Abnormal urination, such as urinary urgency, frequent urination, difficult urination, dysuria, nocturia, etc. Normal or elevated WBC in EPS or VB3, culture‐negative. NIH‐CPSI ≥ 10. Patients who had NOT been treated with NSAIDs or alpha blockers before Exclusion criteria: Patients with gonococcal urethritis or non‐gonococcal urethritis, prostate cancer, hyperplasia of prostate, narrowing of the urethra, urolithiasis, neurogenic bladder, neuropsychiatric disorders, etc., which affected the function of lower urinary tract Sample size: 115 Age (years): Group 1 Mean 31.64 (SD 5.96) Group 2 Mean 33.56 (SD 5.61) Group 3 Mean 32.23 (SD 4.41) NIH‐CPSI baseline score: Group 1 = 23.38 (SD 4.01); Group 2 = 21.58 (SD 3.96); Group 3 = 22.34 (SD 4.21) All participants were men
Interventions	Group 1 (n = 40): Dexketoprofen trometamol (oral, 12.5 mg/tablet) 3 times a day Group 2 (n = 41): Indomethacin (oral, 25 mg) 3 times a day Group 3 (n = 42): only terazosin (see co‐interventions) Co‐interventions: Terazosin (oral, 2 mg) every night Participants in all 3 groups took medications for 4 weeks The second night, the dosage of terazosin for all groups was cut down to a half
Outcomes	Prostatitis symptoms How measured: NIH‐CPSI score and subscore Time points measured: before treatment, after treatment Time points reported: before treatment, after treatment (week 4) Subgroups: none Adverse events How measured: Narratively
Funding sources	Not mentioned
Declarations of interest	Not mentioned
Notes	This study was written in Chinese
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “115 patients were randomly allocated into 3 groups”, (p 826), but the method of randomisation was not reported
Allocation concealment (selection bias)	Unclear risk	Allocation concealment was not described
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Visibly different interventions. Blinding was unlikely
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Visibly different interventions. Blinding was unlikely
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data were available for all participants
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias were detected

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Jung 2006.

Methods	Study design: Parallel‐group randomised trial Study dates: start date January 2004 ‐ end date February 2005 Setting: outpatient ‐ single centre ‐ national Country: South Korea
Participants	Inclusion criteria: men aged ≤ 45 years old with prostate volume ≤ 25 mL, with a clinical diagnosis of CP/CPPS (III) Exclusion criteria: not reported Total number of participants randomly assigned: 127 Age (years): not reported. Wrote to study authors NIH‐CPSI baseline score: Group 1 = 21.8 (SD 5.5); Group 2 = 21.5 (SD 7.4) All participants were men
Interventions	Group 1 (n = 71): Terazosin 3 ‐ 4 mg/day during 12 weeks Group 2 (n = 56): No treatment Co‐interventions: levofloxacin 300 mg/day, tamiflunate 3 tablets/day for 12 weeks
Outcomes	Prostatitis Symptoms How measured: NIH CPSI questionnaire score and subscores Time points measured: baseline and 12 weeks after treatment Time points reported: baseline and 12 weeks after treatment
Funding sources	Ilyang Pharmaceutical
Declarations of interest	Not reported
Notes	Language of publication: Korean E‐mail: ircho@ilsanpaik.ac.kr (email bounced)
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. Wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. Wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	No information available. Wrote to study authors
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	No information available. Wrote to study authors
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data were available for all participants
Selective reporting (reporting bias)	Unclear risk	Protocol not available. Wrote to study authors
Other bias	Low risk	No other sources of bias detected

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Kaplan 2004.

Methods	Study design: Parallel‐group randomised trial Study dates: Not available Setting: outpatient ‐ single centre ‐ national Country: USA
Participants	Inclusion criteria: (Consensus criteria Alexander 2004a) age > 18 years old suffering from pelvic pain or discomfort for at least 3 months during the 6 months before entry, NIH‐CPSI > 20 and pain subscore > 4 Exclusion criteria: urinary tract infection in the previous 6 months, a history of cancer, neurological disorders, previous urological surgery, diabetes, nephrolithiasis, urinary retention and no medical treatment recently prescribed (alpha blockers, antibiotics and anti‐inflammatory drugs for 4 weeks and 5‐alpha‐reductase inhibitors for at least 6 months) Sample size: 64 were randomised Age (years): Group 1 mean 42.9 (SD 11.2); Group 2 mean 43.5 (SD 10.1) Baseline NIH‐CPSI score: Group 1 mean 24.7 (5.3); Group 2 mean 23.9 (5.7) All participants were men
Interventions	Group 1 (n = 32): Serenoa repens (saw palmetto) 325 mg daily for 12 months Group 2 (n = 32): finasteride 5 mg daily for 12 months Co‐interventions: not described
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline, 3, 6 and 12 months Time points reported: graphically; numerically in the abstract for total score Urinary Symptoms How measured: AUA score Time points measured: baseline, 3, 6 and 12 months Time points reported: subscore at 12 months Adverse events How measured: Narratively
Funding sources	Not available
Declarations of interest	Not available
Notes	Main findings were presented graphically. The total number randomised and the available at follow‐up were available, but there is no information about how many were allocated to each group (we assumed 32 in each group). We wrote to study authors (sk46@columbia.edu) but the email bounced
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available
Allocation concealment (selection bias)	Unclear risk	No information available
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	The study is described as single‐blind; but it is not specified who was blinded; participants or personnel could have been blinded
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	The study is described as single‐blind; but it is not specified who was blinded
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: there were 31, 29 and 28 participants evaluated at 3, 6 and 12 months, respectively, in the saw palmetto group, and 30, 28 and 28 were evaluated at 3, 6, 12 months in the finasteride group. Balanced attrition, at 3‐month follow‐up, missing outcome data < 10%
Selective reporting (reporting bias)	High risk	Most data were presented graphically, total NIH‐CPSI score in the abstract with no information on standard deviation. P values were selectively reported
Other bias	Low risk	No other sources of bias were identified

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Kim 2003.

Methods	Study design: Parallel‐group randomised trial Study dates: start date June 2001 ‐ end date March 2002 Setting: Outpatient ‐ single centre ‐ national Country: South Korea
Participants	Inclusion criteria: men aged ≥ 20 and ≤ 50 years old with symptoms of chronic prostatitis, with a clinical diagnosis of CP/CPPS (IIIb) Exclusion criteria: men with positive culture in urine or EPS, or positive culture in PCR (Chlamydia trachomatis, Trichomonas vaginalis, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum) Total number of participants randomly assigned: 63 Age: not reported. Wrote to study authors NIH‐CPSI baseline score: Group 1 = 18.83 (SD 6.57); Group 2 = 18.00 (SD 5.81); Group 3 = 18.09 (SD 6.75) All participants were men
Interventions	Group 1 (n = 18): tamsulosin (0.2 mg orally every day) Group 2 (n = 15): ibuprofen (600mg tid po) with Misoprostol (300 mcg orally 3 times a day) Group 3 (n = 22): tamsulosin (0.2 mg orally every day) + ibuprofen (600 mg orally 3 times a day) with Misoprostol (300 mcg orally 3 times a day) Duration: 8 weeks Co‐interventions: not described
Outcomes	Prostatitis Symptoms How measured: NIH CPSI questionnaire Time points measured: baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks after treatment Time points reported: baseline, 12 weeks after treatment Adverse events: clinically significant (not defined) How measured: visit to outpatient clinic
Funding sources	Not reported
Declarations of interest	Not reported
Notes	Language of publication: Korean Contact information. E‐mail: cyh0831@catholic.ac.kr
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “randomly assigned the patients consecutively”. Comment: The authors did not clarify the details in Korean. Wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. Wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	No information available. Wrote to study authors
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	No information available. Wrote to study authors
Incomplete outcome data (attrition bias)   All outcomes	High risk	All outcomes: missing outcome data in 8/63 due to follow‐up loss (no information on loss)
Selective reporting (reporting bias)	High risk	Analysis intentions are not available Favorable outcomes for the experimental intervention were likely to report in results (e.g. Qmax) and subdomains of NIH‐CPSI were omitted. Results of multiple measurements at different time points were omitted
Other bias	Unclear risk	No information of baseline characteristics

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Kim 2008.

Methods	Study design: Parallel‐group randomised trial Study dates: Not reported Setting: Outpatient ‐ single centre ‐ national Country: South Korea
Participants	Inclusion criteria: men aged ≥ 20 and ≤ 40 years old (mainly) with symptoms of discomfort or pain in the pelvic region for at least a 3‐month period, with negative urine or EPS culture. Participant has a clinical diagnosis of CP/CPPS (III). Participant with NIH‐CPSI has reported total score of 8 or more (pain domain must be 4 or more) Exclusion criteria: men with a history of neurogenic bladder or lower urinary tract surgery, or positive culture on urine or EPS culture. Men with prior treatment of chronic prostatitis or BPH. Men suspected prostate cancer or BPH on DRE Total number of participants randomly assigned: 46 Group 1 age (years): 40.8 ± 7.9 Group 2 age (years): 39.4 ± 8.2 NIH‐CPSI baseline score: Group 1 = 22.6 ± 4.2; Group 2 = 23.1 ± 5.2 All participants were men
Interventions	Group 1 (n = 31): propiverine (20 mg, once daily) for 2 months Group 2 (n= 15): only co‐intervention for 2 months Co‐interventions: all participants received gatifloxacin 200 mg, twice a day
Outcomes	Prostatitis Symptoms How measured: NIH CPSI questionnaire Time points measured: start, 1 month and 2 months Time points reported: start, 1 month and 2 months Subgroups: no Urinary Symptoms How measured: IPSS questionnaire Time points measured: start, 1 month and 2 months Time points reported: start, 1 month and 2 months Subgroups: no Adverse events How measured: Narratively
Funding sources	Grant from Dankook University
Declarations of interest	Not reported
Notes	Language of publication: Korean Contact information: e‐mail: killtumor@yahoo.co.kr
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. Wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. Wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	Single‐blinded: No information given, but usually participants were blinded in single‐blinded fashion. Wrote to study authors
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	Single‐blinded: No information given, but usually outcome assessors were blinded in single‐blinded fashion. Wrote to study authors.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data were available for all participants
Selective reporting (reporting bias)	Unclear risk	Analysis intentions are not available Clinically significant AEs were reported without the definition of which AEs counted as clinically significant. Clinically significant AEs were likely to be favourable outcomes to the experimental intervention. Wrote to study authors
Other bias	Low risk	No other sources of bias were detected

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Kim 2011a.

Methods	Study design: Parallel‐group randomised trial Study dates: 01 March 2008 to 28 February 2009 Setting: outpatient ‐ multicentre ‐ national Country: Republic of Korea
Participants	Inclusion criteria: Age < 55 years. Diagnosis of chronic prostatitis/chronic pelvic pain syndrome; “pain or discomfort in the pelvic region for at least 3 months, a total score of at least 12 on the NIH‐CPSI and anticipated improvement of symptoms with therapy.” Exclusion criteria: "urinary tract infection determined by urine study, hypoechoic lesions on transrectal ultrasonography (TRUS), a serum PSA level of 3 ng/dL or more, or a history of disease that could have affected the results of this study” Sample size: 107 randomised Age (years): Group A: mean 45.7; Group B: mean 46.5; Group C: mean 46.1 Baseline NIH‐CPSI score: Group A: mean 23.6 ± 5.5; Group B: mean 23.9 ± 5.9; Group C: mean 23.17 ± 5.5 All participants were men
Interventions	Group A (n = 40): Only co‐interventions Group B (n = 32): 50 mg of diclofenac twice daily for 12 weeks Group C (n = 28): 500 mg of ciprofloxacin twice daily for 12 weeks Co‐interventions: All participants underwent 2 weeks of wash‐out time from the first visit. All participants received tamsulosin 0.2 mg once daily for 12 weeks
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score and subscore Time points measured: baseline and 12 weeks after treatment Time points reported: baseline and 12 weeks after treatment Urinary symptoms How measured: International Prostate Symptom Score (IPSS) Time points measured: baseline and 12 weeks after treatment Time points reported: baseline and 12 weeks after treatment
Funding sources	Not available
Declarations of interest	none
Notes	Email: urogate@dau.ac.kr
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “Patients were enrolled to subgroup by the table of random sampling digit in each medical center.” Comment: No additional information provided. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information provided. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Quote: "We did not have placebo group, because the effects of each drugs such as a‐blocker, antibiotics and non‐steroidal anti‐inflammatory drugs were widely known to the standard drug for CP/CPPS treatment"
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Open‐label study
Incomplete outcome data (attrition bias)   All outcomes	High risk	5 participants excluded from analysis since they received “other anti‐inflammatory drugs or antibiotics while the study was in progress.” Additionaly, “Two patients opted for transurethral resection of the prostate.” Comment: No information available for what treatment arm they were assigned to
Selective reporting (reporting bias)	Unclear risk	No protocol available. We wrote to study authors
Other bias	Unclear risk	Some baseline characteristics were missing. We wrote to study authors

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Kim 2011b.

Methods	Study design: Parallel‐group randomised trial Study dates: study dates not available Setting: outpatient ‐ multicentre ‐ national Country: South Korea
Participants	Inclusion criteria: men aged 20 to 49 years old (to exclude benign prostate hyperplasia) diagnosed with CP/CPPS and with pelvic pain for 3 or more months, negative urine and prostate secretions cultures, post‐voiding residual volume < 100 mL, maximum urinary flow rate > 15 mL/sec or more and a total NIH‐CPSI score of 8 or more and an NIH‐CPSI pain score of 4 or more at baseline Exclusion criteria: prostate surgery, use of 5α‐reductase inhibitors for 3 or more months, anticholinergic use within 6 months of baseline, elevated PSA level (> 4.0 ng/mL), prostatic cancer, urethral stricture, diabetes mellitus, neurogenic bladder and hypersensitivity to ciprofloxacin or solifenacin Sample size: 96 randomised Age (years): Not available Baseline NIH‐CPSI score: Group 1 = 19.8 ± 6.4; Group 2 = 22.4 ± 6.0 All participants were men
Interventions	Group 1 (n = 49): only co‐intervention Group 2 (n = 47): solifenacin 5 mg daily for 8 weeks Co‐interventions: ciprofloxacin 1000 mg daily for 8 weeks
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score and subscores Time points measured: baseline, 4 weeks and 8 weeks Time points reported: baseline, 4 weeks and 8 weeks Urinary Symptoms How measured: IPSS score Time points measured: baseline, 4 weeks and 8 weeks Time points reported: baseline, 4 weeks and 8 weeks Sexual Dysfunction How measured: IIEF score Time points measured: baseline, 4 weeks and 8 weeks Time points reported: baseline, 4 weeks and 8 weeks
Funding sources	Not available
Declarations of interest	Quote: “No potential conflict of interest relevant to this article was reported”
Notes	Contact information: killtumor@yahoo.co.kr (Hyung‐Jee Kim)
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Single‐blind study.
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Single‐blind study, it is not clear whether this included participants, however there were visibly different interventions. Blinding was unlikely (outcome assessors)
Incomplete outcome data (attrition bias)   All outcomes	High risk	The Methods section stated that they recruited 49 participants in the ciprofloxacin group and 47 in the ciprofloxacin+solifenacin group, but outcome data (all outcomes) were available for 40 and 47 participants respectively. The authors have not specified the reasons for missing outcome data. We wrote to them asking for information
Selective reporting (reporting bias)	Unclear risk	No protocol available. We wrote to study authors
Other bias	Unclear risk	Baseline characteristics were not available. Small differences in baseline NIH‐CPSI score between groups

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Kong 2014.

Methods	Study design: Parallel‐group randomised trial Study dates: Not available Setting: outpatient ‐ single centre ‐ national Country: South Korea
Participants	Inclusion criteria: participants with CP/CPPS type III Exclusion criteria: symptoms lasting for < 3 months, proven urinary tract infection, invasive prostate‐related procedures (transurethral resection of the prostate, transurethral incision of the prostate, or transurethral needle ablation), LUTS without significant pain, significant signs and symptoms of obstructive voiding, or prostate volume of > 50 cm³ Sample size: 88 Age (years): Group 1 = 44.2 ± 6.9 years; Group 2 = 45.3 ± 7.0 years Baseline NIH‐CPSI score: Group 1 = 22.1 ± 1.5; Group 2 = 19.5 ± 1.6 All participants were men
Interventions	Group 1 (n = 40): only co‐interventions Group 2 (n = 48): Mirodenafil 50 mg daily for 6 weeks Co‐interventions: All participants received levofloxacin 500 mg daily for w6eeks
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline and at 6 weeks Time points reported: baseline and at 6 weeks (change from baseline) Urinary Symptoms How measured: IPSS score Time points measured: baseline and at 6 weeks Time points reported: baseline and at 6 weeks (change from baseline) Sexual Dysfunction How measured: International Index of Erectile Function 5 (IIEF‐5) Time points measured: baseline and at 6 weeks Time points reported: baseline and at 6 weeks (change from baseline) Adverse Events How measured: Narratively only for group 2
Funding sources	Pusan National University Hospital Clinical Research Grants (2014)
Declarations of interest	Not available
Notes	Contact: Hyun Jun Park. E‐mail: joon501@naver.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Single‐blind trial
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	Single‐blind trial. No information about whether participants were blinded
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data were available for all participants
Selective reporting (reporting bias)	Unclear risk	No protocol available. We wrote to study authors
Other bias	Unclear risk	Small differences in baseline NIH‐CPSI score between groups

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Kulovac 2007.

Methods	Study design: Parallel‐group randomised trial Study dates: start date January 2004 ‐ end date November 2004 Setting: outpatient ‐ single centre ‐ national Country: Bosnia and Herzegovina
Participants	Inclusion criteria: CP/CPPS was diagnosed after blood tests, urinary and sperm cultures Exclusion criteria: urinary tract infection, suspicion of prostate cancer, acute prostatitis, urethral disease, calculosis of the lower urinary tract, identified allergy to 1 of the medications, diagnosed psychiatric disorder, diabetes, kidney insufficiency, consumption of medications that affected voiding Sample size: 90 participants randomised Age (years): overall mean 40.3 (SD 8.23) NIH‐CPSI baseline score: overall mean 25.8 (SD 4.8) All participants were men
Interventions	Group 1 (n not available): ciprofloxacin 2 doses of 500 mg daily for 30 days Group 2 (n not available): doxazosin 2 mg daily for 30 days Group 3 (n not available): ciprofloxacin + doxazosin daily for 30 days Co‐interventions: none described
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline and after treatment Time points reported: baseline and after treatment
Funding sources	Not available
Declarations of interest	Not available
Notes	Contact information: www.researchgate.net/scientific‐contributions/33546794_Benjamin_Kulovac
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “patients were distributed in the three groups at random” Comment: no other information available. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	Quote: “patients were distributed in the three groups at random” Comment: no other information available. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Quote: “Prospective, comparative, open, clinical, manipulative study”
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Quote: “Prospective, comparative, open, clinical, manipulative study”
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Quote: “Patient list was made for all the patients in whom all the results were included.” Comment: No follow‐up information was reported. We wrote to study authors
Selective reporting (reporting bias)	High risk	The number of participants in each group was not reported. Baseline subscores were measured but they were not reported after treatment
Other bias	Unclear risk	Limited baseline characteristics

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Lacquaniti 1999.

Methods	Study design: Parallel‐group randomised trial Study dates: start date May 1997 ‐ end date October 1998 Setting: outpatient ‐ single centre ‐ national Country: Italy
Participants	Inclusion criteria: participants suffering from non‐bacterial prostatitis Exclusion criteria: patients with positive cultures of urine and prostate secretions; patients were evaluated to “exclude concurrent urinary diseases” Sample size: 80 patients randomised Age (years): mean 36.19 (SD 11.53) NIH‐CPSI baseline score: Not available All participants were men
Interventions	Group 1 (n not available): terazosine 5 mg daily for 60 days Group 2 (n not available): Tamsulosin 0.4 mg daily for 60 days Group 3 (n not available): placebo daily for 60 days Co‐interventions: No antibiotics were administered.
Outcomes	Prostatitis Symptoms How measured: PSSI (0 to 12 score) at 60 days Adverse events How measured: narratively
Funding sources	Not available
Declarations of interest	Not available
Notes	Email not available
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was done using a “computer‐generated list”
Allocation concealment (selection bias)	Unclear risk	No information available
Blinding of participants and personnel (performance bias)   Subjective outcomes	Low risk	Participants were blinded. Study doctors were blinded. Drugs were packaged in “anonymous boxes”
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Participants were blinded. Drugs were packaged in “anonymous boxes”
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	There is no information about how many participants had outcome data (all outcomes)
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Unclear risk	There is no information about how many participants were in each group

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Lee 2005.

Methods	Study design: Parallel‐group randomised trial Study dates: study dates not available Setting: outpatient ‐ single centre ‐ national Country: United Kindom
Participants	Inclusion criteria: individuals with symptoms compatible with CPPS Exclusion criteria: individuals with urethritis or positive prostate culture, symptoms suggestive of benign prostatic hyperplasia or significant abnormalities on baseline bloods were excluded. Additionally, current treatment with an antidepressant or anxiolytic drug, history of seizures, or any history of hypersensitivity or intolerance to a selective serotonin reuptake inhibitor were exclusion criteria Sample size: 14 participants randomised Age (years): not available. We wrote to study authors Baseline NIH‐CPSI score (PSS score): Group 1 = 23.4; Group 2 = 28 All participants were men
Interventions	Group 1 (n = 7): Sertraline 50 mg daily for 13 weeks. They were then unblinded and continued for a total of 26 weeks Group 2 (n = 7): Placebo. At 13 weeks they were offered the opportunity to cross over to sertraline Co‐interventions: Not described
Outcomes	Prostatitis Symptoms How measured: validated prostatic symptom frequency (PSF) and prostatic symptom severity (PSS) score Time points measured: 6, 13, 26 weeks Time points reported: 13 weeks (blinded), 26 weeks (unblinded) Anxiety and Depression How measured: Hospital Anxiety and Depression (HAD) scale, and a psychosexual (Psex) questionnaire Time points measured: 6, 13, 26 weeks Time points reported: 13 weeks (blinded), 26 weeks (unblinded) Sexual Dysfunction How measured: Psychosexual (Psex) questionnaire (unclear validity) Time points measured: 6, 13, 26 weeks Time points reported: 13 weeks (blinded), 26 weeks (unblinded) Adverse Events How measured: Narratively
Funding sources	Quote: “MSSVD for funding the manufacture of the matched placebo used in this study”
Declarations of interest	None
Notes	14 participants were randomised and divided “equally”; we assume 7 in each group R A Lee, email: rachel.lee@leedsth.nhs.uk (email bounced)
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	Double‐blind study; it is not clear who was blinded. We wrote to study authors
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Participants seem to have been blinded due to the use of a matched placebo.
Incomplete outcome data (attrition bias)   All outcomes	High risk	All outcomes: 1 participant was lost to follow‐up in the placebo group (very small trial)
Selective reporting (reporting bias)	Unclear risk	Protocol not available. We wrote to study authors
Other bias	Low risk	No other sources of bias were identified

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Lee 2006a.

Methods	Study design: Parallel‐group randomised trial Study dates: start date October 2003 ‐ end date April 2004 Setting: outpatient ‐ single centre ‐ national Country: Korea
Participants	Inclusion criteria: men aged 18 or older with CP/CPPS, NIH‐CPSI pain subscore of 4 or more, and a urinary subscore of 3 or less, with reported pain in the pelvic region for at least 3 months. Exclusion criteria: bacterial prostatitis, bacteriuria in the last three months, a history of cancer, neurological disorders, urological surgery, diabetes, abnormal digital rectal examination except for benign enlargement, nephrolithiasis, urinary retention and an abnormal peak urinary flow. Antibiotics, alpha blockers, a‐adrenergic agents, anticholinergic, antispasmodic or muscle relaxants, cimetidine, warfarin and herbal medications were interrupted 4 weeks prior the start of the study Sample size: 50 randomised Age (years): Group 1 mean 44.2 (SD 2.1); Group 2 mean 42.7 (SD 2.9) NIH‐CPSI (baseline): Group 1 mean 21.62 (SD 4.2); Group 2 mean 22.12 (SD 6.0) All participants were men
Interventions	Group 1 (n = 25): terpene mixture rowatinex® 200 mg (pinene 31%, camphene 15%, anethol 4%, borneol 10%, cineol 3% and fenchone 4% in olive oil) 3 times a day during 6 weeks Group 2 (n = 25): ibuprofen 600 mg 3 times a day during 6 weeks Co‐interventions: all participants underwent a 2‐week wash‐out period from previous analgesic medications
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: during wash‐out period, “baseline”, 15 days and 6 weeks Time points reported: 6 weeks, other time points were reported graphically Adverse Events How measured: Narratively
Funding sources	Not available
Declarations of interest	Not available
Notes	S. W. Kim. E‐mail: cyh0831@catholic.ac.kr
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	“Single blind”, at least participants or personnel were not blinded
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	“Single blind”, it’s not clear if participants were blinded. Visibly different interventions, blinding was unlikely
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	No information available. We wrote to study authors
Selective reporting (reporting bias)	High risk	Scores were presented graphically at most time points and in those who were reported, they did not include measure of variability (e.g. SD). We wrote to study authors
Other bias	Low risk	No other sources of bias were identified

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Leskinen 1999.

Methods	Study design: Parallel‐group assignment randomised trial Study dates: not available Setting: outpatient ‐ single centre ‐ national Country: Finland
Participants	Inclusion criteria: individuals who presented with subjective symptoms of pain and discomfort associated with the genitourinary tract and in the external genitalia, as well as irritative bladder symptoms; they were evaluated with urine sample after prostatic massage and included those who contained 10 or more white blood cells. All patients had received antibiotic regimens for their symptoms from their own doctors, with no relief Exclusion criteria: Urethritis, benign prostate hyperplasia, Evidence of prostate cancer, history of infection in the urinary tract Sample size: 41 Age (years): Placebo 46 years (range 33 ‐ 61); Finasteride 47 (range 32 ‐ 61) Baseline NIH‐CPSI score: not available All participants were men
Interventions	Placebo (n = 10): placebo 12 months. Medication was taken once‐a‐day in the morning before breakfast Finasteride (n = 31): finasteride 5 mg daily for 12 months. Medication was taken once‐a‐day in the morning before breakfast Co‐interventions: ketoprofene was provided to both group for pain relief. All participated had a 4‐week placebo tablets run‐in period
Outcomes	Prostatitis Symptoms How measured: PSSI Time points measured: −1 (baseline), 0, 1, 3, 6, 12 months Time points reported: −1 (baseline), 0, 1, 3, 6, 12 months Urinary Symptoms How measured: IPSS Time points measured: −1 (baseline), 0, 1, 3, 6, 12 months Time points reported: −1 (baseline), 0, 1, 3, 6, 12 months Adverse Events How measured: Narratively
Funding sources	None
Declarations of interest	None
Notes	Randomisation was 3:1. No contact information available
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available
Allocation concealment (selection bias)	Unclear risk	No information available
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	“Double blind”, It was not specified who was blinded
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	“Double blind”, It was not specified who was blinded
Incomplete outcome data (attrition bias)   All outcomes	High risk	All outcomes: 12% attrition in finasteride group, 20% attrition in placebo group
Selective reporting (reporting bias)	High risk	No protocol available. The rate of sexual adverse events was reported only in the finasteride group (narratively)
Other bias	Low risk	No other sources of bias were identified

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Li 2003.

Methods	Study design: Parallel‐group randomised trial Study dates: start date June 2002 ‐ end date December 2002 Setting: outpatient ‐ single centre ‐ national Country: China
Participants	Inclusion criteria: Age 20 to 50, patients who had symptoms of chronic prostatitis; course of disease: 3 months to 5 years, NIH‐CPSI ≥ 10, in the past 1 month, no history of antibiotics treatment because of infection of the urinary tract or any other reasons; in the past 1 week, patients did not take any drugs for treating chronic prostatitis or drugs that affect urination Exclusion criteria: Patients with neurogenic bladder, narrowing of the urethra, benign prostate hyperplasia, prostate cancer, urinary infection, tuberculosis, calculi, or other diseases that affect urination; Patients with serious diabetes, cardiovascular diseases, or insufficiency of the liver or kidney; Patients with psychiatric disorders, habitual diarrhoea, or inflammatory bowel disease Sample size: 125 participants, 76 with type III prostatitis Age (years): Overall 20 ˜ 50; mean 32.7 Baseline NIH‐CPSI score: Group 1 = 25.45 (SD 5.82); Group 2 = 22.87 (SD 5.79) All participants were men
Interventions	Group 1 (n = 41 with type III prostatitis): QianLieAnShuan (Prostat), rectal administration, 1 tablet each time, administer once every night for 30 days Group 2 (n = 35 with type III prostatitis): Substrate for QianLieAnShuan (placebo), rectal administration, 1 tablet each time, administer once every night for 30 days Co‐interventions: A wash‐out period of 7 days for all participants. Discontinue any other medications for prostatitis, including antibiotics, alpha blockers, TCM drugs, herbal medications, etc. Discontinue any other treatment options
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI Time points measured: before treatment, Day 30 Time points reported: before treatment, Day 30 Adverse Events How measured: Narratively
Funding sources	Not mentioned
Declarations of interest	Not mentioned
Notes	This study was written in Chinese. No contact information available
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “randomized, double‐blinded, placebo‐controlled, and multi‐center clinical trial” and “patients were randomly divided into trial group and control group” Comment: the exact method of randomisation is unknown
Allocation concealment (selection bias)	Unclear risk	Quote: “randomized, double‐blinded, placebo‐controlled, and multi‐center clinical trial”. Comment: The exact method for allocation concealment is not described
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	Blinding of participants and personnel is not described
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	Blinding of outcome assessment is not described
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: 1 patient in the active treatment group was lost to follow‐up, very low attrition
Selective reporting (reporting bias)	Unclear risk	Protocol not available
Other bias	Low risk	No other sources of bias were detected

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Li 2007.

Methods	Study design: Parallel‐group randomised trial Study dates: start date July 2004 ‐ end date January 2006 Setting: outpatient ‐ single centre ‐ national Country: China
Participants	Inclusion criteria: Patients who meet the diagnostic criteria for Chronic Pelvic Pain Syndrome. 2‐glass test: urine microscopy and culture for bacteria negative. Prostate fluid negative for Chlamydia, mycoplasma, fungi, and trichomonas. WBC in prostate fluid < 10/HP AND seminal WBC < 5/HP Exclusion criteria: Age > 40. Patients with tuberculosis of the prostate. Patients with prostate cancer Sample size: 108 participants Age (years): Group 1 (20 ˜ 40, Mean ± SD: 30.6 ± 5.3); Group 2 (21 ˜ 44, Mean ± SD: 29.3 ± 5.1) Baseline NIH‐CPSI score: Group 1 mean 26.3 (SD 4.9); Group 2 mean 25.8 (SD 5.1) All participants were men
Interventions	Group 1 (n = 56): Ingredients of 1 dose of Tiaoshen Tonglin decoction were decocted by machine, and packed into 2 bags (150 mL each), taking 1 bag (150mL) in the morning on an empty stomach and the other before going to bed, for 60 days Group 2 (n = 52): Terazosin hydrochloride tablet 2 mg once a day (before going to bed) for 60 days Co‐interventions: All other medications discontinued
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: before treatment, after treatment Time points reported: before treatment (60 days) Subgroups: none Adverse Events How measured: Narratively
Funding sources	Key Project of the Science and Technology Department of Hebei Province (Project No. 052761143)
Declarations of interest	Not mentioned
Notes	This study was written in Chinese. Email: libodoc@126.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “108 patients … were stratified by course of disease(≤ 3 months, 3˜12 months, ≥12 months) and Maximum Flow Rate(MFR, ≥15mL/s, <15mL/s), numbered according to date of admission, and randomly assigned to two groups by referring to random sequence chart” (p 252). Comment: We wrote to study authors.
Allocation concealment (selection bias)	Unclear risk	Allocation concealment was not described. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Masking of participants and personnel was not described. However, considering the visible difference between the two interventions, masking was unlikely
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Blinding was unlikely (visibly different interventions)
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data were available for all participants
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias were detected

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Li 2012.

Methods	Study design: Parallel‐group randomised trial Study dates: start date October 2010 ‐ end date March 2011 Setting: outpatient ‐ single centre ‐ national Country: China
Participants	Inclusion criteria: Patients were included with reference to NIH‐CPSI, i.e. patients with long‐term and recurrent pain or discomfort of the pelvic area, with or without urinary symptoms or sexual dysfunction, course of disease > 3 months, “Two‐glass test” culture for bacteria negative Exclusion criteria: Patients with other diseases of the lower urinary tract, psychiatric disorders or other serious conditions Sample size: 257 patients (37 lost to follow‐up) Age (years): Total (18 ˜ 42, mean ± SD: 30.6 ± 6.4) Baseline NIH‐CPSI score (mean±SD): Group 1 = 25.9 ± 5.8; Group 2 = 23.7 ± 6.7; Group 3 = 24.8 ± 7.2 All participants were men
Interventions	Group 1 (n = 98): Qianlieping capsule (2.0 g per capsule), by mouth, 3 times a day. Tamsulosin (0.2 mg), by mouth, once a day, for 6 weeks Group 2 (n = 56): Tamsulosin (0.2 mg), by mouth, once a day for 6 weeks Group 3 (n = 66 ): Qianlieping capsule (2.0 g per capsule), by mouth, 3 times a day for 6 weeks Co‐interventions: Not mentioned
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI, number of lecithin body in prostatic fluid Time points measured: before treatment, after treatment Time points reported: before treatment, after treatment (Week 6) Subgroups: none
Funding sources	1. Special project in Henan‐provincial Key Disciplines and Specialties of Traditional Chinese Medicine Academic Leaders Cultivation Program (2013ZY03032) 2. Zhengzhou Municipal Projects on Science and Technology Innovation Team (121PCXTD)
Declarations of interest	Not mentioned
Notes	This study was written in Chinese. Email: glutljp@163.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “Patients were randomly allocated into 3 groups upon complete informed consent” (p 857) Comment: The method of randomisation was not reported. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	Allocation concealment was not described. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Masking of participants and personnel was not described. However, it is easy for participants to know which intervention they are taking
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Blinding could not be achieved when assessing participant‐reported outcomes
Incomplete outcome data (attrition bias)   All outcomes	High risk	Outcome data (all outcomes) of 37/257 patients were missing (14% attrition). Not specified study arm
Selective reporting (reporting bias)	Unclear risk	No protocol available. We wrote to study authors
Other bias	Low risk	No other sources of bias were detected

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Lin 2007.

Methods	Study design: Parallel‐group randomised trial Study dates: not available Setting: outpatient ‐ single centre ‐ national Country: China
Participants	Inclusion criteria: Patients met the diagnostic criteria for CP/CPPS, complicated by erectile dysfunction; NIH‐CPSI symptoms subscore ≥ 9, EPS culture negative; IIEF‐5 ≤ 21 Exclusion criteria: Prostate tumour, other urogenital diseases, diabetes, hyperlipidaemia, chronic insufficiency of the liver or the kidney, severe disorders of cardiovascular system, infectious diseases, severe neurologic or psychiatric disorders Sample size: 138 participants Age (years): Group 1, trial group: 24 ˜ 51, mean 36; Group 2, control group: 23 ˜ 53, mean 38 NIH‐CPSI baseline score: Group 1 = 28.3 ± 4.5; Group 2 = 27.4 ± 7.6 All participants were men
Interventions	Group 1 (n = 70): Starting from Week 5: Vardenafil 10 mg once a day, taken orally, 30 mins before having sexual intercourse, for 8 weeks Group 2 (n = 68): Only co‐interventions Co‐interventions: Huafenqinutang orally twice a day; course of treatment: 8 weeks Discontinue any drugs for treating CP/CPPS and ED 2 weeks before and during the trial, including antibiotics, alpha blockers, TCM drugs, herbal medications, antidepressants, or neuropsychiatric medications
Outcomes	Prostatitis Symptoms How measured: drop in NIH‐CPSI (significantly effective: 60% ‐ 80%; effective: 30% ‐ 60%; not effective: < 30%) Time points measured: the end of Week 4, the end of Week 8 Time points reported: the end of Week 4, the end of Week 8 Subgroups: None Sexual Dysfunction How measured: IIEF‐5 (significantly effective: > 21; effective: 15 ‐ 20; not effective: < 10 ‐ 15) Time points measured: the end of Week 4, the end of Week 8 Time points reported: the end of Week 4, the end of Week 8 Subgroups: None Adverse events How measured: Narratively
Funding sources	Not reported
Declarations of interest	Not reported
Notes	This study was written in Chinese Email: achang333@126.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “138 patients were randomized to 2 groups” (in Chinese) Comment: It is unclear what method of randomisation was used. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Not described. However, considering the visible difference between the interventions of the 2 groups (2 drugs vs 1 drug), blinding could not be achieved
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Blinding of outcome assessment is not described. In participant‐reported outcomes, however, participants are not blinded
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data were available for all participants
Selective reporting (reporting bias)	Unclear risk	No protocol available. We wrote to study authors
Other bias	Low risk	No other sources of bias were identified

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Lu 2004.

Methods	Study design: Parallel‐group randomised trial Study dates: start date October 2000 ‐ end date March 2001 Setting: outpatient ‐ single centre ‐ national Country: China
Participants	Inclusion criteria: Patients who met the criteria of non‐bacterial prostatitis (NIH‐IIIa) according to the first International Prostatitis Collaborative Network Workshop (November 5 ‐ 6, 1998, Washington DC); Age > 20 AND at least 3 months after clinical diagnosis (pelvic or perineal pain or discomfort within the 3 months before inclusion is required) Exclusion criteria: Patients with infection of the urinary system or positive urine culture results, benign prostate hyperplasia, suspected prostate cancer (screening by PSA); Patients with other acute diseases or severe diseases of the heart, brain, liver, kidney or haematopoietic system Sample size: 60 participants Age (years): Group 1 “Bensylyt (Phenoxybenzamine Hydrochloride)” (22 ˜ 48, Mean ± SD: 39.8 ± 4.5) Group 2 “flavoxate hydrochloride” (23 ˜ 49, Mean ± SD: 38.5 ± 4.2) Group 3 “placebo” (23 ˜ 48, Mean ± SD: 39.1 ± 4.3) Baseline NIH‐CPSI score: Group 1 = 21.95 (SD 3.49); Group 2 = 21.75 (SD 4.27); Group 3 = 21.85 (SD 3.95) All participants were men
Interventions	Group 1 (n = 20): Placebo tablet (compound tablet of starch and Vitamin C, looks the same as Bensylyt) orally, twice a day for 1 month Group 2 (n = 20): Phenoxybenzamine (Bensylyt) tablet (10 mg) orally, twice a day for 1 month Group 3 (n = 20): Flavoxate hydrochloride (200mg) orally, three times a day for 1 month Co‐interventions: During the trial, all other options or medications for treating prostatitis were discontinued, including physical therapy, antibiotics, traditional Chinese medicine, etc.
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI Time points measured: before treatment, week 2, week 4, after treatment Time points reported: before treatment, after treatment Subgroups: none Adverse Events Possible adverse events were described but not their incidence
Funding sources	Special project of Ministry of Health (WKZ‐2000‐16)
Declarations of interest	Not mentioned
Notes	This study was written in Chinese No contact information available
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “starting from one particular row, the numbers (which do not end with zero) on a random sequence chart were assigned to patients according to their date of admission; patients assigned to numbers that end with 1˜3, 4˜6, and 7˜9 were assigned to Group I, II, and III respectively.” (p 170)
Allocation concealment (selection bias)	Unclear risk	Allocation concealment was not described
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	In the Discussion, Quote: “when designing this trial, we intended to do a double‐blinded, randomized, placebo‐controlled prospective clinical trial. However, due to technical problems, the placebo used in this trial was a combination of starch and Vitamin C, with the same appearance and method of administration as phenoxybenzamine hydrochloride tablet. We failed to acquire a placebo which has the same appearance and usage as flavoxate HCI‐neptumus.” (p 171)
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Blinding could not be achieved when assessing participant‐reported outcomes
Incomplete outcome data (attrition bias)   All outcomes	High risk	3/20 participants in placebo group dropped out because of serious symptoms of the disease. Outcome data (all outcome) not available for these participants. (p 170)
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias detected

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Macchione 2017.

Methods	Study design: Parallel‐group randomised trial Study dates: start date January 2016 ‐ end date August 2016 Setting: outpatient ‐ single centre ‐ national Country: Italy
Participants	Inclusion criteria: participants with CP/CPPS Exclusion criteria: patients who received medical treatment for lower urinary tract symptoms, major concomitant diseases and with residual urine volume > 50 ml were not included in this study Sample size: total randomised not available Age (years): not available NIH‐CPSI baseline score: not available All participants were men
Interventions	Group 1 (n = 29): Deprox 500 mg 2 tablets a day for 6 weeks Group 2 (n = 34): Serenoa repens 320 mg 1 tablet a day for 6 weeks Co‐interventions: not available
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline, 6 weeks Time points reported: baseline, 6 weeks Urinary Symptoms How measured: IPSS score Time points measured: baseline, 6 weeks Time points reported: baseline, 6 weeks
Funding sources	None
Declarations of interest	Not available
Notes	Abstract only
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available
Allocation concealment (selection bias)	Unclear risk	No information available
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	The interventions were visibly different, blinding was unlikely
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	The interventions were visibly different, blinding was unlikely
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Abstract only (no information available)
Selective reporting (reporting bias)	Unclear risk	Abstract only (no information available)
Other bias	Unclear risk	Abstract only (no information available)

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Maurizi 2019.

Methods	Study design: parallel group randomized trial Study dates: start date March 2016 – end date June 2016 Setting: outpatient, national, single centre Country: Italy
Participants	Inclusion criteria: the presence of persistent pelvic pain for at least 3 months, in the 6 months preceding the study according to the EAU guidelines; NIH‐CPSI pain score greater than 7 and a negative Meares‐Stamey test. Exclusion criteria: age < 18 or > 65 years old; presence of anatomical abnormalities of the urinary tract system; additional urologic diseases; post‐void residual urine volume > 50 cc; known allergy to the experimental treatment; participants who underwent (< 4 weeks) oral or parenteral antibiotics treatment or who were using prophylactic antibiotic treatment (< 4 weeks); positivity to Chlamydia Trachomatis test, Ureaplasma Urealyticum, Neisseria Gonorrhoeae, Herpes Virus (HSV 1/2) and Human Papillomavirus (HPV). Sample size: 54 participants randomized Age (years): Group 1 mean (SD) 34 ± 5.9 years Group 2 mean (SD) 33.7 ± 4.62 years NIH‐CPSI baseline score: Group 1 mean (SD) 25.67 ± 1.62 Group 2 mean (SD) 25.96 ± 1.63 Sex (M/F): All participants were men
Interventions	Group 1 (n = 27): flower pollen extract, two tablets in a single daily dose for four weeks: each dose contained 1 g of pollen extract and B1, B6, B2, B 9, B12, and PP vitamins. Group 2 (n = 27): quercetin (500 mg) complex twice daily for four weeks Co‐interventions: none described
Outcomes	Prostatitis symptoms How measured: NIH‐CPSI score Time points measured: baseline, 4 weeks Time points reported: baseline, 4 weeks Urinary symptoms How measured: IPSS score Time points measured: baseline, 4 weeks Time points reported: baseline, 4 weeks Adverse events How measured: Narratively
Funding sources	The study states “non‐sponsored”.
Declarations of interest	The authors declare no conflict of interest.
Notes	Contact information: Angela Maurizi, MD (Corresponding Author) angmau81@hotmail.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. We wrote to study authors.
Allocation concealment (selection bias)	Unclear risk	No information available. We wrote to study authors.
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Only the patients were blinded to the type of treatment.
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Quote: "The patients enrolled were blinded to the type of treatment."
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data were available for all participants.
Selective reporting (reporting bias)	Unclear risk	Protocol not available.
Other bias	Low risk	No other sources of bias were identified.

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Mehik 2003.

Methods	Study design: Parallel‐group randomised trial Study dates: study dates not available Setting: outpatient ‐ multicentre ‐ national Country: Finland
Participants	Inclusion criteria: participants fulfilling the diagnostic criteria of type III CP/CPPS, NIH‐CPSI score > 11 and pain score > 4 Exclusion criteria: patients with a history of symptoms for < 3 months, proven urinary tract infection during the past year, antibiotic treatment during the preceding 6 months were excluded, those who had undergone invasive prostate‐related procedures (transurethral resection of the prostate, transurethral incision of the prostate, transurethral needle ablation), patients who reported lower urinary tract symptoms without significant pain, patients with significant signs and symptoms of obstructive voiding, and patients with prostate volumes > 40 cm³ were also excluded Sample size: 40 participants randomised Age (years): Group 1 mean 49; Group 2 mean 50 NIH‐CPSI baseline score: Group 1 mean 26; Group 2 mean 23 All participants were men
Interventions	Group 1 (n = 19): alfuzosin 5 mg twice daily for 6 months Group 2 (n = 21): identical placebo in the same posology Co‐interventions: Quote: “Patients in the alfuzosin and placebo groups were allowed to take analgesics (ibuprofen, ketoprofen, diclofenac) up to three times daily for a maximum of 7 days during the 6‐month initial evaluation period, but antibiotics, 5‐alpha‐reductase inhibitors, and alpha‐blockers were not allowed in any of the three groups”
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline, 2, 4, 6, 9 and 12 months Time points reported: baseline, 6 months and 12 months, responders Adverse Events How measured: Narratively
Funding sources	Partially funded by NIH‐NIDDK (R01 DK5374601) Quote: “The study drugs, including the placebo, were supplied by Leiras OY, Turku, Finland. The tablets were packed and blinded by the pharmacy of the University of Helsinki.”
Declarations of interest	Quote: “J. C. Nickel is a paid consultant to, and study investigator funded by, Sanofi‐Synthelabo”
Notes	This was a pilot study. A third group of 30 participants who refused randomisation was included in the study (data not included in this review). Email: jcn@queensu.ca
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	No information available in the paper. The author communicated that the randomisation sequence was centrally generated
Allocation concealment (selection bias)	Low risk	No information available in the paper. The author communicated that the allocation was concealed
Blinding of participants and personnel (performance bias)   Subjective outcomes	Low risk	Participants were blinded with the use of placebo. The author specified that personnel were blinded too
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Participants were blinded with the use of placebo
Incomplete outcome data (attrition bias)   All outcomes	High risk	All outcomes: data were available: At 6 months: 17/19 participants in the alfuzosin group, 20/21 placebo At 12 months: 16/19 participants in the alfuzosin group, 20/21 placebo Unbalanced loss of outcome data
Selective reporting (reporting bias)	High risk	Some time points were not presented, and those presented had no standard deviation. Adverse events were presented as “No patients dropped out of the study because of an adverse event.”
Other bias	Low risk	No other sources of bias were identified

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Mo 2006.

Methods	Study design: Parallel‐group randomised trial Study dates: start date Jan 2004 ‐ end date March 2005 Setting: outpatient ‐ single centre ‐ national Country: South Korea
Participants	Inclusion criteria: men with symptoms of chronic prostatitis and without prior treatment of CP/CPPS. Participant has a clinical diagnosis of CP/CPPS (III). Participant with NIH‐CPSI has reported total score of 15 or more Exclusion criteria: Men with prior treatment of CP/CPPS or BPH, positive culture on urine or EPS culture, or prostate volume ≥ 30 gm on DRE Total number of participants randomly assigned: 54 Age: Group 1 age (years): 44.7 ± 7.5; Group 2 age (years): 45.8 ± 9.6 Baseline NIH‐CPSI score: Group 1 = 23.1 (SD 8.1); Group 2 = 23.9 (SD 8.3) All participants were men
Interventions	Group 1: alfusozin (10 mg, once a day) for 2 months Group 2: only co‐interventions for 2 months Co‐interventions: levofloxacin alone (100 mg, 3 times a day)
Outcomes	Prostatitis Symptoms How measured: NIH CPSI questionnaire Time points measured: baseline, 2 months after treatment Time points reported: baseline, 2 months after treatment Subgroups: no Adverse events How measured: Narratively
Funding sources	Not reported
Declarations of interest	Not reported
Notes	Language of publication: Korean. Email: delommd@hanmail.net
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	No information available. We wrote to study authors
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	No information available. We wrote to study authors
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	No information available. We wrote to study authors
Selective reporting (reporting bias)	Unclear risk	Protocol not available. We wrote to study authors
Other bias	Low risk	No other sources of bias were identified

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Morgia 2010.

Methods	Study design: Parallel‐group randomised trial Study dates: start date September 2006 ‐ end date March 2007 Setting: outpatient ‐ multicentre ‐ national Country: Italy
Participants	Inclusion criteria: men with type IIIA CP/CPPS with NIH‐CPSI score > 15, WBC count > 10, age 20 ‐ 50 Exclusion criteria: proven urinary tract infection in the last year, antibiotic treatment or other medications (non‐steroidal anti‐inflammatory drugs or corticosteroids therapy, alfuzosin, tamsulosin, doxazosin, terazosin, anticholinergics, finasteride, or dutasteride) during the previous 6 months; prior prostate surgery; urogenital diseases; neurologic disease affecting the bladder Sample size: 102 patients randomised Age (years): Group 1 mean 40.96 (SD 8.33); Group 2 mean 35.9 (SD 6.76) NIH‐CPSI baseline score: Group 1 mean 27.45 (SD 5); Group 2 mean 27.76 (SD 3.3) All participants were men
Interventions	Group 1 (n not available): a capsule of Profluss which consisted of 320 mg of S. repens oil extract (85%), 5 mg oil extracted lycopene (6%) 50 ug seleniated sodium for 8 weeks Group 2 (n not available): a capsule of 320 mg of S. repens for 8 weeks  Co‐interventions: Not available
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline, 4, 8 and 16 weeks Time points reported: baseline, 4, 8 and 16 weeks (graphically in the latter case) Urinary Symptoms How measured: IPSS score Time points measured: baseline and 16 weeks Time points reported: baseline and 16 weeks (graphically in the latter case) Adverse events How measured: Narratively
Funding sources	Not available
Declarations of interest	Not available
Notes	Prof. Carlo Magno. E‐Mail cmagno@unime.it
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “Patients were divided by a computerized, centralized randomization into two equally sized groups”
Allocation concealment (selection bias)	Low risk	Quote: “Patients were divided by a computerized, centralized randomization into two equally sized groups”
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	“Double‐Blind”, did not fully describe the masking process. We wrote to study authors
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	“Double‐Blind”, did not fully describe the masking process. We wrote to study authors
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: “All enrolled patients completed this study.”
Selective reporting (reporting bias)	High risk	Primary outcome was presented without variability measurement; some time points were only presented graphically
Other bias	Unclear risk	Number of participants in each arm are not available. We wrote to study authors

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Morgia 2017.

Methods	Study design: Parallel‐group randomised trial Study dates: start date June 2015 ‐ end date January 2016 Setting: outpatient ‐ single centre ‐ national Country: Italy
Participants	Inclusion criteria: participants aged 20 to 50 with symptoms of pelvic pain for 3 months or more, negative 4‐glass test, Meares‐Stamley test and a total NIH‐CPSI score ≥ 15 Exclusion criteria: participants with urinary tract infections, sexually transmitted diseases, treatment with phytotherapeutic agents, alpha blockers, antibiotics and urogenital cancer Sample size: 55 participants Age (years): Group 1 median 32 (IQR 29 ‐ 38); Group 2 median 32 (IQR 28.75 ‐ 38.75) NIH‐CPSI baseline score: Group 1 median 20.5 (IQR 15 ‐ 24.5); Group 2 median 20 (IQR 15 ‐ 25) All participants were men
Interventions	Group 1 (n = 27): rectal suppositories of curcumin extract 350 mg (95%) and calendula extract 80 mg, 1 suppository daily for 1 month Group 2 (n = 28): identical looking placebo suppositories in the same regimen Co‐interventions: not available
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline and 12 weeks Time points reported: baseline and 12 weeks Sexual Dysfunction How measured: IIEF score, PEDT score Time points measured: baseline and 12 weeks Time points reported: baseline and 12 weeks Adverse Events How measured: narrative, only in the placebo group
Funding sources	None
Declarations of interest	No conflict of interests declared
Notes	None
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available
Allocation concealment (selection bias)	Unclear risk	No information available
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Single‐blind study, only participants were blinded
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Participants were blinded
Incomplete outcome data (attrition bias)   All outcomes	High risk	All outcomes: outcome data were available in 24/27 participants in group A and in 24/28 participants in group B
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias were detected

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Nickel 2003a.

Methods	Study design: Parallel‐group randomised trial Study dates: study dates not available Setting: outpatient ‐ multicentre ‐ national Country: Canada
Participants	Inclusion criteria: participants of 18 years of age who had experienced symptoms of discomfort or pain in the pelvic region for at least 3 months during the 6 months before study entry, and had no documented history of cystitis or positive cultures in the past 12 months and had not been receiving any antibiotic treatment for any reason in the previous month. In addition, all participants had to discontinue all analgesic medications for a minimum of 1 week and no changes in any prostatitis‐specific medication in the previous 4 weeks was allowed Exclusion criteria: see Alexander 2004 Sample size: 80 Age (years): Group 1 = 56,2 years (range 36 to 78); Group 2 = 56 years (39 to 77) Baseline NIH‐CPSI score: Group 1 = 21.3 (SD 7.2); Group 2 = 24.4 (SD 8.2) All participants were men
Interventions	Group 1 (n = 35): placebo 1 tablet a day during 6 weeks Group 2 (n = 45): levofloxacin 500 mg a day during 6 weeks Co‐interventions: not described
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI Time points measured: baseline, 3, 6 weeks Time points reported: baseline, 3, 6 weeks Adverse Events How measured: Narratively
Funding sources	Janssen‐Ortho Canada and the National Institutes of Health
Declarations of interest	Not available
Notes	Email: jcn@queensu.ca
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “The medications were prepackaged according to a computer‐generated, randomized allocation schedule”
Allocation concealment (selection bias)	Low risk	Quote: “The medications were prepackaged according to a computer‐generated, randomized allocation schedule”
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	“Double blind” study, but who was blinded is not defined (not specified whether personnel were blinded). We wrote to study authors and to the NIH/NIDDK but they could not provide additional data
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Participants were blinded with the use of placebo
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: 1 participant withdrew from the study (not specified study arm)
Selective reporting (reporting bias)	Low risk	Protocol not available. We wrote to study authors and to the NIH/NIDDK but they could not provide additional data
Other bias	Low risk	No other sources of bias detected

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Nickel 2003b.

Methods	Study design: Parallel group randomised trial Study dates: study dates not available Setting: outpatient ‐ multicenter ‐ international Country: USA and Canada
Participants	Inclusion criteria: patients > 18 years old, with symptoms of discomfort or pain in the pelvic region for at least 3 months during the 6 months before entry, with a score of 4 or more on the NIH‐CPSI average pain score (question 4) for baseline and week 1 Exclusion criteria: "1. Treatment with BCG, or has unilateral orchialgia without pelvic symptoms, active urethral stricture, neurological disease or disorder affecting the bladder, a history of prostate, bladder or urethral cancer, or has a history of pelvic radiation, systemic or intravesical chemotherapy.  2. Serum creatinine is greater than 1.5 times the upper limit of normal.  3. Uncontrolled hypertension.  4. Clinically significant abnormalities on prestudy clinical examination or laboratory safety tests.  5. History of neoplastic disease. 6. Currently a user (including “recreational use”) of any illicit drugs, or has a history (within the past 5 years) of drug or alcohol abuse.  7. Neurological impairment or psychiatric disorder preventing his understanding of consent and his ability to comply with the protocol.  8. History of any illness that, in the opinion of the investigator, might confound the results of the study or pose additional." (sic) Sample size: 161 participants randomised Age (years): Group 1 mean = 45.8 (SD 12); Group 2 mean = 44.1 (SD 12); Group 3 mean = 48 (SD 13.3) NIH‐CPSI baseline score: Group 1 mean = 22.9 (SD 5.2); Group 2 mean = 22.5 (SD 6.5); Group 3 mean = 20.5 (SD 6) All participants were men
Interventions	Group 1 (n = 59): placebo (in the images of rofecoxib 25 and 50 mg) Group 2 (n = 53): rofecoxib 25 mg and placebo (image of 50 mg) Group 2 (n = 49): rofecoxib 50 mg and placebo (image of 25 mg) Co‐interventions: discontinue all previous medication 1 week before taking the study drug, with a 1 week of run‐in period with placebo. All participants were permitted to take up to 2.6 g of paracetamol for rescue analgesia (except the placebo run‐in period)
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: −1, 0, 3 and 6 weeks Time points reported: −1, 0, 3 and 6 weeks Adverse Events How measured: Narratively
Funding sources	Supported by Merck Research Laboratories, White House Station, New Jersey
Declarations of interest	Financial interest and/or other relationship with Merck, Pharmacia, Alza, Ortho‐McNeil, Janssen‐Ortho Canada, Bayer Canada, Sanofi Synthelabo Canada and Glaxo Smith Kline, Boehringer‐ Ingleheim, Zeneca, Abbott, Lilly, Sepracor, Pfizer, Vivus, Nexmed, Praecis, Watson, Unimed, Myriad, Macrochem, Interneuron, Yamanouchi
Notes	Email: jcn@queensu.ca
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “Investigators received randomized blocks of study drug labeled with allocation numbers and balanced by treatment group”
Allocation concealment (selection bias)	Low risk	Quote: “Investigators received randomized blocks of study drug labeled with allocation numbers and balanced by treatment group” (Central allocation)
Blinding of participants and personnel (performance bias)   Subjective outcomes	Low risk	“Double blind” study, but who was blinded is not defined (not specified whether personnel were blinded). We wrote to study authors: personnel were blinded
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Participants were blinded with the use of placebo
Incomplete outcome data (attrition bias)   All outcomes	High risk	Quote: “Four patients were excluded from analysis of the primary end point, NIH‐CPSI pain score, because they provided no data during the 6‐week treatment period and the last value carried forward method was used to estimate data for 20 patients (6 to 7 per group)”
Selective reporting (reporting bias)	High risk	SD was not reported for the identified outcomes in the study
Other bias	Low risk	No other sources of bias were identified

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Nickel 2004a.

Methods	Study design: Parallel‐group randomised trial Study dates: study dates not available Setting: outpatient ‐ multicentre ‐ national Country: USA
Participants	Inclusion criteria: men aged “≥ 18 years and had symptoms of discomfort or pain in the pelvic region for ≥ 3 months during the 6 months before entry.” With “presence of any white blood cells per high‐power microscopic field in the expressed prostatic secretion (EPS) or in the sediment of the post‐prostatic massage urine sample” Exclusion criteria: a history of cystitis with a positive culture of an uropathogen or previous positive culture of expressed prostatic secretion or semen; history of urinary tract cancer, genital herpes, inflammatory bowel disease. Participants who had received chemotherapy or radiation. Participants with unilateral orchialgia with no pelvic symptoms, with active urethral stricture, neurological disease or disorder affecting the bladder, with a neurological impairment or psychiatric disorder preventing his understanding of consent and his ability to comply with the protocol. Participants with a history of any sexually transmitted disease in the past 3 months, a history of TURP, or other transurethral intervention, balloon dilation of the prostate, open prostatectomy, or any other prostate surgery or treatment such as cryotherapy or thermal therapy. Patients who had previously or concurrently received 5a‐reductase therapy Sample size: 76 participants were randomised Age (years): Group 1 mean = 46.9 (SD 1.7, range 27 – 63); Group 2 mean = 41.7, (SD 2.1, range 26 – 71) NIH‐CPSI baseline score: Group 1 = 20.1 (SD 1.4); Group 2 = 22.5 (SD 1.6) All participants were men
Interventions	Group 1 (n= 31): finasteride 5 mg daily for 6 months Group 2 (n= 33): matching placebo for 6 months Co‐interventions: Not available.
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline, 3 and 6 months Time points reported: baseline, 3 and 6 months Adverse Events How measured: Narratively
Funding sources	Quote: “This study was funded by the University Grants Program (Merck Inc.) as an independent investigator initiated research project. All the authors Prostatitis Research Centers are funded by grants from the NIH/NIDDK”
Declarations of interest	Quote: “J.C. Nickel is a study investigator/consultant; D.A. Shoskes is a study investigator. Source of funding: Investigator Initiated Independent Research Grant from Merck.”
Notes	The report states that there were 76 participants, but only 64 were available for outcome assessment. There is no information about how many participants were lost to follow‐up in each study arm. Participants had a placebo run‐in period Email: jcn@queensu.ca
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. We wrote to study authors and to the NIH/NIDDK but they could not provide additional data
Allocation concealment (selection bias)	Unclear risk	No information available. We wrote to study authors and to the NIH/NIDDK but they could not provide additional data
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	No information about blinding of personnel. Participants were blinded (placebo), We wrote to study authors and to the NIH/NIDDK but they could not provide additional data
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Participants were blinded with the use of placebo
Incomplete outcome data (attrition bias)   All outcomes	High risk	All outcomes: the report states that there were 76 participants, but only 64 were available for outcome assessment. There is no information about how many participants were lost to follow‐up in each study arm
Selective reporting (reporting bias)	Unclear risk	No protocol available. We wrote to study authors and to the NIH/NIDDK but they could not provide additional data
Other bias	Low risk	No other sources of bias identified

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Nickel 2004b.

Methods	Study design: Parallel‐group randomised trial Study dates: start date July 2000 ‐ end date May 2001 Setting: outpatient ‐ multicenter ‐ national Country: USA
Participants	Inclusion criteria: men ≤ 55 years old with a diagnosis CP/CPPS; NIH‐CPSI score of 15 or more, pain subscore score of 8 or more at screening and baseline, and pain in the pelvic region for 3 or more months were required for study inclusion Exclusion criteria: participants with chronic or acute bacterial prostatitis, acute urinary retention within 4 weeks of screening, urethral stricture, abnormal digital rectal examination except for benign enlargement, bacteriuria within 3 months of screening, significant urogenital disease, prior prostate surgery or pelvic radiotherapy, abnormal serum chemistries or complete blood count, history of allergy to alpha‐adrenergic antagonists or hypersensitivity to tamsulosin, postural hypotension, cancer diagnosed within 5 years of baseline, finasteride use within 3 months, or significant cardiac, endocrine, or neurological disorders “Medications that could interfere with the study drug or influence symptoms of CP/CPPS were not permitted (such as alpha‐adrenergic blocking drugs, alpha‐adrenergic agents, drugs with anticholinergic activity, antispasmodics or muscle relaxants, parasympathomimetics or cholinomimetics, antibiotics, nonsteroidal anti‐inflammatory drugs, cimetidine, warfarin, herbal medications and intravesical bacillus Calmette‐Guerin)" Sample size: 58 participants randomised Age (years): Group 1 mean = 40.8 (range 21 ‐ 56); Group 2 mean = 40.9 (range 21 ‐ 54) NIH‐CPSI baseline score: Group 1 mean = 26.4 (SD 4.9); Group 2 mean = 26.2 (SD 6.5) All participants were men
Interventions	Group 1 (n = 28): 0.4 mg tamsulosin HCl capsule daily for 6 weeks (days 1 to 45) after a 2‐week wash‐out period with placebo; 30 minutes after breakfast Group 2 (n = 30): matching placebo in the same posology Co‐interventions: Not available
Outcomes	Prostatitis symptoms How measured: baseline, and 6 weeks (day 45) Time points measured: baseline, and 6 weeks (day 45) Adverse events How measured: narratively
Funding sources	Personal communication with the author: Pfizer
Declarations of interest	Not available
Notes	Email: jcn@queensu.ca
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	“sequentially”, no other information available. We wrote to study authors and they confirmed it was generated at random
Allocation concealment (selection bias)	Low risk	No information available. We wrote to study authors and they confirmed that allocation was concealed
Blinding of participants and personnel (performance bias)   Subjective outcomes	Low risk	Participants were blinded, not specified if study personnel were blinded. We wrote to study authors: personnel were blinded
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Participants were blinded using placebo
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes (outcome assessment at 6 weeks) 5/30 participants did not complete study in the placebo group; 2 participants did not complete study in the tamsulosin group, but they included outcome data using "last observation carried forward" (LOCF)
Selective reporting (reporting bias)	Low risk	No protocol available. We wrote to study authors: all outcomes were prespecified and only short‐term data were obtained
Other bias	Low risk	No other sources of bias were identified

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Nickel 2005.

Methods	Study design: Parallel‐group randomised trial Study dates: study dates not available Setting: outpatient ‐ multicentre ‐ international Country: Canada and USA
Participants	Inclusion criteria: Men of 18 to 50 years old with a clinical diagnosis of CP/CPPS at least 3 months in duration, with a score > 6 on questions 1 to 4 and 3 or more on question 4 of the NIH‐ CPSI score Exclusion criteria: a history of cystitis with an associated positive urine culture, prostate, bladder or urethral cancer, genital herpes in the last year, “any sexually transmitted disease in the last 3 months, inflammatory bowel disease, pelvic radiation or chemotherapy, unilateral orchialgia without pelvic symptoms, active urethral stricture; neurological diseases or disorders of the bladder, surgery on or physical treatment of the prostate, renal failure, pelvic or rectal surgery other than hemorrhoidectomy, hemostasis disorders, occult blood in the stool, anticoagulant use, that is greater than 1 gm aspirin or opioids (United States Schedule II), medication for sexual dysfunction, sensitivity to PPS or capsule components and planned surgery during or within 4 weeks of the study.” Sample size: 100 participants randomised Age (years): Group 1 = 40.8 (range 21 ‐ 59); Group 2 = 37.5 (range 25 ‐ 55) NIH‐CPSI baseline score: Group 1 mean = 27.1 (SD 1.1); Group 2 mean = 25.8 (SD 1.13) All participants were men
Interventions	Group 1 (n = 51): Oral pentosan polysulfate sodium capsules of 300 mg 3 times a day for 16 weeks Group 2 (n = 49): Identical‐looking placebo in the same doses for 16 weeks Co‐interventions: not available
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline, 4, 8, 12 and 16 weeks Time points reported: baseline, 4, 8, 12 and 16 weeks Adverse Events How measured: Narratively
Funding sources	Ortho‐McNeil/Alza
Declarations of interest	Financial interest and/or other relationship with Ortho‐McNeil, Bayer, Boehringer‐Ingelheim, Sanofi‐Synthelabo, Merck, Glaxo‐SmithKline, Farr Laboratories, Novartis, Abbott and Lilly/ICOS, Pfizer, and Abbott
Notes	The study used stratified randomisation by disease severity but there was no subgroup analysis by disease severity. ClinicalTrial.gov identifier NCT00236990 refers to a similar study (see studies awaiting classification). Personal contact with the author (Dr. Nickel) could neither confirm nor reject that this is the registration record of the trial Email: jcn@queensu.ca
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “Randomization was stratified according to symptom severity at screening, as measured by the SSI” Comment: no further information was provided
Allocation concealment (selection bias)	Unclear risk	Quote: “Randomization was stratified according to symptom severity at screening, as measured by the SSI” Comment: no further information was provided
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	“double‐blind”, but it was not specified who was blinded (regarding personnel)
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	“double‐blind”, but it was not specified who was blinded; however, identical‐looking placebo was used (participants were blinded)
Incomplete outcome data (attrition bias)   All outcomes	High risk	Quote: “Of the enrolled patients 73% completed the 16‐week study. Of 27 patients who did not complete the study 11 in the PPS group and 4 in the placebo group discontinued due to adverse events or intercurrent illnesses”
Selective reporting (reporting bias)	Unclear risk	Protocol not available (See notes in Characteristics of study)
Other bias	Low risk	No other sources of bias were identified

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Nickel 2008.

Methods	Study design: Parallel‐group randomised trial6 Study dates: start date February 2005 ‐ end date January 2008 Setting: outpatient ‐ multicentre ‐ internationalCountry: United States, Canada and Malaysia
Participants	Inclusion criteria: participants who had signed the informed consent, male aged 18 years of older who had symptoms of discomfort or pain in the pelvic region for at least 6 weeks and symptoms being present in the last 2 years Exclusion criteria: Participants with positive gram‐negative or enterococcus culture of midstream urine, previous treatment with the study drug or other alpha blockers in the past 2 years, presence of a history of prostate, penile, testicular, bladder, or urethral cancer or has undergone pelvic radiation, systemic chemotherapy, or intravesical chemotherapy, moderate or severe hepatic impairment, severe renal sufficiency, severe or unstable cardiovascular, respiratory, hematological, endocrinological, neurological or other somatic disorders, those who had unilateral orchialgia without pelvic symptoms, active urethral stricture, or neurological disease or disorder affecting the bladder. Additional criteria were uninvestigated, significant haematuria, previous treatment with TURP, TUIP, TUIBN, TUMT, TUNA, balloon dilation of the prostate, open prostatectomy or any other prostate surgery or treatment such as cryotherapy or thermal therapy. Participants with neurological impairment or psychiatric disorder preventing his understanding of consent and his ability to comply with the protocol Due to medication interactions, those who were taking potent CYP3A4 inhibitors Sample size: 272 participants randomised Age (years): Group 1 mean = 40.1 (SD 12.3); Group 2 = 40.1 (SD 11.4) Baseline NIH‐CPSI score: Group 1 mean = 25.1 (SD 5.9); Group 2 = 23.8 (SD 6.3) All participants were men
Interventions	Group 1 (n = 138): alfuzosin 10 mg once daily for 12 weeks Group 2 (n = 134): identical‐looking placebo of the same posology Co‐interventions: not specified
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline and 12 weeks Time points reported: baseline and 12 weeks Adverse events How measured: All were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Time points measured: baseline, 6 and 12 weeks Time points reported: baseline and 12 weeks Sexual Dysfunction How measured: IIEF and Male Sexual Health Questionnaire Time points measured: baseline and 12 weeks Time points reported: baseline and 12 weeks Quality of Life How measured: SF‐12 Time points measured: baseline and 12 weeks Time points reported: baseline and 12 weeks Depression and Anxiety How measured: Hospital Anxiety and Depression scale Time points measured: baseline and 12 weeks Time points reported: baseline and 12 weeks
Funding sources	Quote: “sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, and Sanofi‐Aventis provided the study drug and placebo at no cost. Sanofi‐Aventis was not involved in the design of the study, the analysis of the data, or the preparation of the manuscript”
Declarations of interest	"Dr. Nickel reports receiving a lecture fee from Sanofi‐Aventis, consulting fees from Pfizer and Farr Labs, and research support from Allergan and American Medical Systems; Drs. O’Leary and Landis, receiving consulting and advising fees from Sanofi‐Aventis; Dr. Krieger, receiving consulting and advising fees from Pfizer; Dr. Alexander, receiving lecture fees from Boehringer Ingelheim; Dr. Shoskes, receiving consulting fees from Farr  Labs and holding stock in Triurol; Dr. Kusek, holding stock in Eli Lilly, Pfizer, and deCODE Genetics; and Dr. Schaeffer, receiving consulting fees from Alita Pharmaceuticals, NovaBay Pharmaceuticals, IMS Health, and Regeneron and lecture fees from the Wright Resource and cme2. No other potential conflict of interest relevant to this article was reported"
Notes	ClinicalTrials.gov number: NCT00103402. Email: jcn@queensu.ca
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “with the use of a centrally controlled, web based data‐management system. A permuted‐block randomization procedure with randomly assigned block sizes of 4, 6, and 8 was used”
Allocation concealment (selection bias)	Low risk	Quote: “with the use of a centrally controlled, web based data‐management system. A permuted‐block randomization procedure with randomly assigned block sizes of 4, 6, and 8 was used”
Blinding of participants and personnel (performance bias)   Subjective outcomes	Low risk	Participants received identical‐looking matched placebo and study investigators were unaware of the treatment assignments
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Participants were blinding using placebo
Incomplete outcome data (attrition bias)   All outcomes	High risk	Loss of follow‐up CPSI Experimental 22 (15.9%) placebo 17/134 (13.6%)/ IIEF 28/138 (20.3%) placebo 25/134 (18.7%)/ SF12 Experimental 23/138 (16.7%) placebo 21/134 (15.7%)/ Depression Experimental 23/138 (16.7%) placebo 17/134 (12.7%)
Selective reporting (reporting bias)	Low risk	Outcomes matched those described in the clinical trial registry
Other bias	Low risk	No other sources of bias were identified

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Nickel 2011a.

Methods	Study design: Parallel‐group randomised trial Study dates: start date September 2008 ‐ end date October 2009 Setting: outpatient ‐ multicentre ‐ national Country: Canada
Participants	Inclusion criteria: Men at least 18 years of age, total NIH‐CPSI total score of 15, NIH‐CPSI pain score of 8 with pain in the pelvic region for at least 3 months prior to screening Exclusion criteria: previous experience with silodosin or alpha blockers or participated in an investigation in the last 30 days, ≥ 2 urinary tract infections within the previous 12 months, the presence of medical condition that in the opinion of the investigator precludes safe participation in the study or could confound the efficacy evaluation. Concurrent use of ketoconazole, or other known potent inhibitors of cytochrome P450 3A4 or any medication in the opinion of the investigator that precludes safe participation in the study or could confound the efficacy evaluation Sample size: 151 participants randomised Age (years): Group 1 mean = 49.2 (SD 13.3); Group 2 = 46.7 (SD 15.6); Group 3 = 49 (SD 11.6) NIH‐CPSI baseline score: Group 1 mean = 26 (SD 6.3); Group 2 mean = 26.8 (SD 5.9); Group 3 mean = 27.9 (SD 6.2) All participants were men
Interventions	Group 1 (n = 52): Silodosin 4 mg daily for 12 weeks Group 2 (n = 45): Silodosin 8 mg daily for 12 weeks Group 3 (n = 54): Daily placebo Co‐interventions: Not specified
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline, 4, 8 and 12 weeks. Time points reported: baseline and 12 weeks Quality of life How measured: SF‐12 Time points measured: baseline, 4, 8 and 12 weeks. Time points reported: baseline and 12 weeks Adverse events How measured: Narratively
Funding sources	Watson Laboratories, Inc
Declarations of interest	Quote: “Financial interest and/or other relationship with GlaxoSmithKline, Johnson & Johnson, Pfizer, Watson, Taris Biomedical, Ferring, Farr Labs, Triton, Trillium Therapeutics and Astellas.”
Notes	Clinical Trial Registry: NCT00740779 Email: jcn@queensu.ca
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomisation schedule created by the sponsor. Not specified how it was generated. We wrote to study authors: the authors had no data on this topic
Allocation concealment (selection bias)	Low risk	Central pharmacy allocation
Blinding of participants and personnel (performance bias)   Subjective outcomes	Low risk	Both participants and personnel were blinded using placebo
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Participants were blinded using placebo
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	All outcomes: 43/52, 31/45 and 41/54 of participants in each study arm completed the study. The results are reported as intention‐to‐treat, but it is unclear if all participants had outcome data at 12 weeks follow‐up. We wrote to study authors: the authors had no data on this topic
Selective reporting (reporting bias)	Low risk	Outcomes matched clinical trial registry
Other bias	Low risk	No other sources of bias were identified

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Nickel 2016.

Methods	Study design: Parallel‐group randomised trial Study dates: start date March 2009 ‐ start date March 2010 Setting: outpatient ‐ multicentre ‐ national Country: USA, Canada, France, Sweden and Switzerland
Participants	Inclusion criteria: Diagnosis of chronic prostatitis, men at least 18 years of age, moderate to severe chronic prostatitis (total NIH‐CPSI score ≥ 15), with an average pain score above a predefined level; to use contraception Exclusion criteria: History of symptoms for < 3 of the last 6 months, recurrent urinary tract infections, or genito‐urinary cancer, use of finasteride or dutasteride within 6 months, history of hepatitis B, C or human immunodeficiency virus (HIV) Sample size: 62 participants randomised Age (years): Group 1 mean = 50.5 (SD 11.9); Group 2 mean = 43.2 (SD 13.5) NIH‐CPSI baseline score: Not available. All participants were men
Interventions	Group 1 (n = 30): single dose of 20 mg of IV tanezumab (monoclonal antibody directed against the pain‐mediating neurotrophin, nerve growth factor) Group 2 (n = 32): single dose of IV placebo Co‐interventions: All other medications for CP/CPPS were permitted provided they had started using it > 3 months before screening
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline, 6 weeks, 16 weeks Time points reported: baseline, 6 weeks, 16 weeks Adverse events How measured: Narratively
Funding sources	Quote: “This study was sponsored by Pfizer, Inc.; editorial/medical writing support was provided by Joseph Oleynek of UBC Scientific Solutions and was funded by Pfizer, Inc.”
Declarations of interest	Quote: “J. C. Nickel is a consultant/investigator for GlaxoSmithKline, Johnson & Johnson, Pfizer, Inc., Watson Pharmaceuticals, Ferring Pharmaceuticals, Tocris Bioscience, Farr Laboratories, Astellas Pharma, Triton Pharma, Trillium Therapeutics, and Eli Lilly; M. Pontari is a consultant for Eli Lilly and Azcan; D. A. Shoskes is a consultant for Farr Laboratories and an investor in, and receives compensation from, Triurol; G. Atkinson, I. W. Mills, and T. J. Crook are employees of, and hold stock or options, in Pfizer, Inc. J. N. Krieger declares that he has no relevant financial interests”
Notes	This is part of a series of 3 trials Study A4091010 (ClinicalTrials.gov identifier: NCT00601484) tanezumab vs placebo in patients with IC/BPS Study A4091035 (ClinicalTrials.gov identifier: NCT00999518) tanezumab in 200 patients with IC/BPS. Study A4091019 (ClinicalTrials.govidentifier: NCT00826514) tanezumab vs placebo in male patients with CP/CPPS (data was extracted for this trial from three journal articles and the clinical trial record) Participants had a run‐in period Quote: “Patients were stratified according to their baseline mean daily NRS “average” pain (moderate, 4 to <7; severe, ≥7)”, this was not reported in outcomes Email: jcn@queensu.ca
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Central randomization "The subject’s daily pain numeric ratings scale (NRS) was collected via interactive voice response system (IVRS) commencing from the evening of the first day of the screening assessment period, and was used to assess inclusion into the study and to determine stratification at randomization" (Clinical trial record) EUCTR2008‐004861‐25‐SE.
Allocation concealment (selection bias)	Low risk	Central allocation (see above)
Blinding of participants and personnel (performance bias)   Subjective outcomes	Low risk	Participants and personnel were blinded
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Participants were blinded (using placebo)
Incomplete outcome data (attrition bias)   All outcomes	High risk	Outcome data (NIH‐CPSI score) were available for 25/30 and 26/32 of participants in Groups 1 and 2 respectively For adverse events, the denominator in the table mentions complete outcome data (low risk of bias)
Selective reporting (reporting bias)	High risk	NIH‐CPSI scores are not reported; only change from baseline. The report states that the measurement of NIH‐CPSI score extended to 16 weeks, but the report only mentions 6 weeks
Other bias	High risk	Editorial support was provided by Pfizer (industry bias)

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Okada 1985.

Methods	Study design: Parallel‐group randomised trial Study dates: March 1983 to August 1983 Setting: outpatient ‐ multicentre ‐ national Country: Japan
Participants	Inclusion criteria: Non‐specific chronic prostatitis patients. Diagnosis was determined by subjective symptoms, observation of the prostate palpation site, urethral secretion after the prostatic gland muscle and urine findings comprehensively Exclusion criteria: No detail Sample size: 76 Age (years): No details Baseline NIH‐CPSI score: not available. All participants were men
Interventions	Group 1 (n = 32): PPCI (aminoacid preparation) 6 capsules daily and placebo C agent 6 tablets daily divided in three doses, one after each meal, 2 capsules and 2 tablets were administered concomitantly Group 2 (n = 30): C agent (probably pollen extract) 6 tablets a day, PPC placebo 6 capsules daily divided in three doses, one after each meal, 2 capsules and 2 tablets were administered concomitantly Co‐interventions: not available. Interventions probably lasted 4 weeks (follow‐up period)
Outcomes	None of the outcomes prespecified in this review
Funding sources	No details
Declarations of interest	No details
Notes	No email available
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No details in the text. Insufficient information to make judgement
Allocation concealment (selection bias)	Low risk	Test drugs and control drugs are randomly allocated and distributed by a control roller (Hirakata citizen Role of pharmacist Sano Yukiro Hospital). Central allocation
Blinding of participants and personnel (performance bias)   Subjective outcomes	Low risk	Each drug had a placebo version, identical in appearance
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Each drug had a placebo version, identical in appearance
Incomplete outcome data (attrition bias)   All outcomes	High risk	All outcomes: outcome data available for: Group 1: n = 32 (84.2%), Group 2: n = 30 (78.9%), Dropout: n = 14
Selective reporting (reporting bias)	Unclear risk	The protocol was not available
Other bias	Low risk	No other sources of bias identified

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Park 2005.

Methods	Study design: Parallel‐group randomised trial Study dates: start date November 2002 ‐ end date September 2003 Setting: outpatients ‐ single institute ‐ national Country: South Korea
Participants	Inclusion criteria: men with symptoms of discomfort or pain in the pelvic region for at least a 3‐month period. Participant has a clinical diagnosis of CP/CPPS (IIIb). After 8 weeks conventional treatment (run‐in), men with symptom improvement and WBC < 10/HPF in EPS were included Exclusion criteria: Before 8 weeks conventional treatment, men with WBC ≥ 10/HPF in EPS, a positive urine analysis or culture, or positive EPS culture Total number of participants randomly assigned: 50 Age: Group 1 (years): 36.2 (24 ‐ 45); Group 2 (years): 35.2 (23 ‐47) Baseline NIH‐CPSI score: Group 1 = 23.1 (SD 4.4); Group 2 = 22.4 (SD 3.7) All participants were men
Interventions	Group 1: Cranberry Juice (Ocean Spray^®) 150 mL twice a day for 12 weeks Group 2: No treatment during the same time Co‐interventions: all participants underwent an 8 week‐run‐in period with levofloxacin 100m g 3 times a day, NSAID, Alpha blocker, behaviour therapy, and hot sitz bath. For non‐responders, 4 weeks of same treatments were added
Outcomes	Prostatitis Symptoms How measured: NIH CPSI questionnaire Time points measured: baseline, 12 weeks after treatment Time points reported: baseline, 12 weeks after treatment Subgroups: no Adverse events How measured: Narratively
Funding sources	Not reported
Declarations of interest	Not reported
Notes	Language of publication: Korean E‐mail: bonstone@ewha.ac.kr
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Participants in the control group did not receive placebo, while those in the treatment group received intervention
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Participants in the control group did not receive placebo, while those in the treatment group received intervention
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data were available for all participants
Selective reporting (reporting bias)	Unclear risk	No protocol available. We wrote to study authors
Other bias	High risk	Active run‐in (After 8 weeks conventional treatment, men with symptom improvement and WBC < 10/HPF in EPS were included)

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Park 2012.

Methods	Study design: Parallel‐group randomised trial Study dates: not available Setting: outpatient ‐ single centre ‐ national Country: South Korea
Participants	Inclusion criteria: not available Exclusion criteria: not available Sample size: 78 Age (years): Group 1 = 41.2 ± 6.7 years Group 2 = 43.3 ± 7.1 years Baseline NIH‐CPSI score: not available All participants were men
Interventions	Group 1 (n = 40): Only co‐intervention Group 2 (n = 38): tadalafil 10 mg daily for 4 weeks Co‐interventions: Levofloxacin 500 mg daily for 4 weeks
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline and at 4 weeks Time points reported: baseline and at 4 weeks Urinary Symptoms How measured: IPSS Time points measured: baseline and at 4 weeks Time points reported: baseline and at 4 weeks Sexual Dysfunction How measured: International Index of Erectile Function 5 (IIEF‐5) Time points measured: baseline and at 4 weeks Time points reported: baseline and at 4 weeks Adverse events How measured: Narratively
Funding sources	None
Declarations of interest	Not available
Notes	We extracted this information from an abstract presentation; We contacted the author: Dr Park (joon501@naver.com) and he mentioned that there was no publication available
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available
Allocation concealment (selection bias)	Unclear risk	No information available
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	No information available
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	No information available
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	No information available
Selective reporting (reporting bias)	Unclear risk	No information available
Other bias	Unclear risk	No information available

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Park 2017.

Methods	Study design: Paralle‐ group randomised trial Study dates: study dates not available Setting: outpatient ‐ single centre ‐ national Country: South Korea
Participants	Inclusion criteria: men with NIH diagnosis of CP/CPPS Exclusion criteria: not available Sample size: 86 participants randomised Age (years): Group 1 = 49.2 (SD 6.7); Group 2 = 48.3 (SD 7.1) NIH‐CPSI baseline score: Not available All participants were men
Interventions	Group 1 (n = 40): only co‐interventions Group 2 (n = 46): tadalafil 5 mg/day for 6 weeks Co‐interventions: Levofloxacin 500 mg daily for 6 weeks
Outcomes	Prostatitis symptoms How measured: NIH‐CPSI score Time points measured: baseline, 6 weeks Time points reported: change from baseline at 6 weeks Urinary symptoms How measured: IPSS score Time points measured: baseline, 6 weeks Time points reported: change from baseline at 6 weeks Sexual dysfunction How measured: IIEF score Time points measured: baseline, 6 weeks Time points reported: change from baseline at 6 weeks Adverse events How measured: narrative, only in tadalafil arm
Funding sources	Not available
Declarations of interest	Not available
Notes	From abstract of the Proceedings of the EAU
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not available (abstract only)
Allocation concealment (selection bias)	Unclear risk	Not available (abstract only)
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	The abstract states “single‐blind”
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	The abstract states “single blind”, but it is unclear how participants were blinded (visibly different interventions)
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Not available (abstract only)
Selective reporting (reporting bias)	Unclear risk	Not available (abstract only)
Other bias	Unclear risk	Not available (abstract only)

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Peng 2003.

Methods	Study design: Parallel‐group randomised trial Study dates: start date August 1999 ‐ end date June 2002 Setting: outpatient ‐ possibly single centre ‐ national Country: China
Participants	Inclusion criteria: Not clearly stated. Common characteristics included: perineal pain or discomfort, frequent urination, secretion at the opening of urethra; WBC/EPS > 10/HP, lecithin body < + + /HP, urine and EPS bacterial culture‐negative Exclusion criteria: Patients with narrowing of the urinary tract, hyperplasia of the prostate, or prostate tumour; patients with serious primary diseases of the cardiovascular system, cerebral‐vascular system, liver, kidney, or haemopoietic system; patients with psychiatric disorders; patients who did not meet the diagnostic criteria of non‐bacterial prostatitis, OR patients who did not take medications as instructed Sample size: 160 participants Age (years): Overall: 23 ˜ 49, Age 20 ˜ 29: 61 participants; age 30 ˜ 39: 72 participants; Age 40 ˜ 49: 27 participants Baseline NIH‐CPSI score: not available All participants were men
Interventions	Group A (n = 40): Oral antiphlogistic medicinal granules, 1 pack, 3 times a day; Duration: 30 days Group B (n = 40): Oral antiphlogistic medicinal granules, 1 pack, 3 times a day, plus enema using anti‐inflammatory mixture 100 ‐ 150 mL, 33 ℃, 15 cm into the anus; Duration: 30 days Group C (n = 40): Oral antiphlogistic medicinal granules, 1 pack, 3 times a day, plusrectal administration of anti‐inflammatory capsule; Duration: 30 days Group D (n = 40): Oral antiphlogistic medicinal granules, 1 pack, 3 times a day, plusrectal administration of anti‐inflammatory capsule, plus water bath and fumigation‐and‐washing using anti‐inflammatory mixture 250 mL, 20 ‐ 30 mins; after that, irradiate the lower abdomen using microwave for 15 mins; Duration: 30 days Co‐interventions: Participants were instructed to discontinue all other treatment options during the trial and observational period
Outcomes	There was no report of outcomes relevant to this review
Funding sources	Shantou Municipal Special project in Science and Technology (2001‐52)
Declarations of interest	Not mentioned
Notes	A combination of subjective clinical parameters alongside laboratory findings formed a composite outcome (not relevant for our review) This study was written in Chinese. Email: stpsf@stinfo.net
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “(160 patients with CNP) were randomly assigned to 4 groups: A, B, C, and D” (in Chinese) Comment: However it is not clear what method was used
Allocation concealment (selection bias)	Unclear risk	Allocation concealment is not described
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Blinding of participants and personnel is not described. However, the difference among the 4 interventions is visible, thus blinding cannot be achieved
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Blinding of outcome assessment is not described. Self‐reported outcomes, participants are not blinded
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data were available for all participants
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias detected

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Persson 1996.

Methods	Study design: Parallel‐group randomised trial Study dates: study dates not available Setting: Outpatient ‐ single centre ‐ national Country: Sweden
Participants	Inclusion criteria: participants with a diagnosis of CP/CPPS Exclusion criteria: not available. Sample size: 54 participants randomised Age (years): Not available NIH‐CPSI baseline score: Not available All participants were men
Interventions	Group 1 (n = 20): Placebo twice a day Group 2 (n = 18): Allopurinol 300 mg in the morning and placebo in the evening Group 2 (n = 16): Allopurinol 600 mg (in 2 doses of 300 mg) Treatment duration: after the 240‐day visit or 8 months of treatment Co‐interventions: not available
Outcomes	No outcomes relevant to this review were reported (see Notes)
Funding sources	Not available
Declarations of interest	Not available
Notes	There is a reported 12‐point symptom scale. This scale evaluated symptoms of prostate discomfort. It’s not clear that it’s validated and does not include the domains of the NIH‐CPSI score. Other outcomes were PSA levels and urine parameters.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were randomised using a spreadsheet
Allocation concealment (selection bias)	Low risk	Central allocation (in another country)
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	Double‐blind study. Not specified if personnel were blinded
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Double‐blind study. Participants were blinded using placebo
Incomplete outcome data (attrition bias)   All outcomes	High risk	All outcomes: Only 34 out of the 54 patients completed the study
Selective reporting (reporting bias)	High risk	Most of the data are presented graphically
Other bias	Low risk	No other sources of bias were identified

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Pontari 2010.

Methods	Study design: Parallel‐group randomised trial Study dates: start date 2006 ‐ end date 2007 Setting: outpatient ‐ multicentre ‐ national Country: USA
Participants	Inclusion criteria: men aged > 18 years, with symptoms of discomfort or pain in the pelvic region during at least 3 of the previous 6 months, and had a total score of at least 15 of 43 on the NIH‐CPSI at screening and randomisation visits approximately 2 weeks apart Exclusion criteria: kidney insufficiency, thrombocytopenia, allergy to any anti‐seizure medication, known sensitivity to pregabalin, treatment with thiazolidinedione or antidiabetic agents, NYHA class III or IV congestive heart failure, a history of thrombocytopenia or bleeding diathesis, and a history of alcohol abuse. “Participants were not excluded if they had previous treatment for CP/CPPS or for taking analgesics for another condition if they continued to have pelvic pain despite the analgesic therapy and had a score of at least 15 on the NIH‐CPSI. Previous treatment with gabapentin or pregabalin was allowed if it was completed at least 2 weeks before study enrolment.” Sample size: 324 Age (years): Group 1 mean = 48 (SD 13); Group 2 mean = 45.2 (SD 12.2) NIH‐CPSI baseline score: Group 1 mean = 26.2 (SD 5.6); Group 2 mean = 25.9 (SD 6.1) All participants were men
Interventions	Group 1 (n = 218): pregabalin 150 mg/day (50 mg orally 3 times daily) for 2 weeks, then 300 mg/day (100 mg orally 3 times daily) for 2 weeks, and then 600 mg/d (200 mg orally 3 times daily) for 2 weeks Group 2 (n = 106): same escalation procedure with placebo Co‐interventions: If a participant could not tolerate the dosage increase, he was allowed to remain at the previous tolerated dosage
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline, and 6 weeks Time points reported: baseline, and 6 weeks Quality of Life How measured: SF‐12 Time points measured: baseline, and 6 weeks Time points reported: baseline, and 6 weeks Anxiety and Depression How measured: Hospital Anxiety and Depression Scale (HADS) Time points measured: baseline, and 6 weeks Time points reported: baseline, and 6 weeks Sexual Dysfunction How measured: IIEF‐Sexual Health Inventory for Men (SHIM) Time points measured: baseline, and 6 weeks Time points reported: baseline, and 6 weeks Adverse Events How measured: Narratively
Funding sources	Quote: “No author received compensation for the performance of this study except as salary support from a grant from the National Institutes of Health. This study was supported by cooperative agreements U01DK65209,UO1DK65268, U01 DK65297, U01 DK65187, U01 DK65277, U01 DK65189, U01 DK65174, U01 DK65266, U01 DK65257, U01 DK65186, and U01 DK65287 from the National Institute of Diabetes and Digestive and Kidney Diseases and the National Center for Minority Health and Health Disparities. Pregabalin and matching placebo capsules were provided by Pfizer Inc.”
Declarations of interest	Consulting fees from Sanofi‐Aventis, Pfizer, GlaxoSmithKline, Pfizer, Bioness Inc, Boston Scientific, Allergan, Astella, Merck, Ortho Women’s Health, Farr Labs, Watson, Medtronic, NeurAxon, and Genyous Biomed, American Medical Systems, Roche, Triuro, Boehringer‐Ingelheim, Decode Genetics, Alita Pharmaceuticals, NovaBay Pharmaceuticals, Regeneron Pharm Inc, IMS Health, Exoxemis Inc, CombinatoRx Inc, Monitor Company Group LP and Advanstar Communications
Notes	Clinicaltrials.gov Identifier: NCT00371033 Email: Pontarm@tuhs.temple.edu
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “randomly assigned 2:1 in each clinical site via a centrally controlled Web‐based data management system to receive treatment with either pregabalin or matching placebo using a permuted block randomization”
Allocation concealment (selection bias)	Low risk	Quote: “randomly assigned 2:1 in each clinical site via a centrally controlled Web‐based data management system to receive treatment with either pregabalin or matching placebo using a permuted block randomization”
Blinding of participants and personnel (performance bias)   Subjective outcomes	Low risk	Quote: “Study investigators and participants were unaware of treatment assignment”
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Quote: “Study investigators and participants were unaware of treatment assignment”
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data were available for all but 8/218 and 3/106 participants in each group
Selective reporting (reporting bias)	Low risk	All outcomes matched the clinical registry
Other bias	Low risk	No other sources of bias were identified

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Reissigl 2004.

Methods	Study design: Parallel‐group randomised trial Study dates: study dates not available Setting: outpatient ‐ multicentre ‐ national Country: Austria
Participants	Inclusion criteria: men with category A CP/CPPS Exclusion criteria: not available Sample size: 142 randomised Age (years): not available NIH‐CPSI baseline score: not available All participants were men
Interventions	Group 1 (n = 72): Permixon (Serenoa repens) Group 2 (n = 70): Placebo Co‐interventions: not described
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline, 6 weeks, 12 weeks, 6, 12 and 18 months Time points reported: none Urinary Symptoms How measured: IPSS score Time points measured: baseline, 6 weeks, 12 weeks, 6, 12 and 18 months Time points reported: none
Funding sources	None
Declarations of interest	Not available
Notes	These characteristics were extracted from an abstract. No full text was available
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available
Allocation concealment (selection bias)	Unclear risk	No information available
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	No information available
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	No information available
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	No information available
Selective reporting (reporting bias)	Unclear risk	No information available
Other bias	Unclear risk	No information available

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Ryu 2007.

Methods	Study design: Parallel‐group randomised trial Study dates: Not reported Setting: Out patients ‐ single institute ‐ national Country: South Korea
Participants	Inclusion criteria: men aged ≥ 20 and ≤ 40 years old (mainly) with symptoms of discomfort or pain in the pelvic region for at least a 3‐month period, with negative urine or EPS culture. Participant has a clinical diagnosis of CP/CPPS (III). Participant with NIH‐CPSI has reported total score of 8 or more (pain domain must be 4 or more) Exclusion criteria: men with a history of neurogenic bladder or lower urinary tract surgery, or positive culture on urine or EPS culture. Men with prior treatment of chronic prostatitis or BPH. Men suspected prostate ca. or BPH on DRE Total number of participants randomly assigned: 57 Age (years) Group 1 = 41.6 ± 9.2 (13 ‐ 53); Group 2 = 38.5 ± 7.8 (31 ‐ 57) The lower range of age for group 1 is 13 in the text, but the correct number might be correct number might be 31 (digit inversion) Baseline NIH‐CPSI score: Group 1 = 21.9 (1.3); Group 2 = 19.5 (1.2) All participants were men
Interventions	Group 1: tosulfoxacin (150 mg, 3 times a day) and alfuzosin (10 mg/day) for 2 months Group 2: tosulfoxacin (150 mg, 3 times a day) for 2 months Co‐interventions: not available
Outcomes	Prostatitis Symptoms How measured: NIH CPSI questionnaire Time points measured: start, 1 month and 2 months of the study Time points reported: start, 1 month and 2 months of the study Subgroups: no Urinary Symptoms How measured: IPSS questionnaire Time points measured: start, 1 month and 2 months of the study Time points reported: start, 1 month and 2 months of the study Subgroups: no Sexual Dysfunction How measured: IIEF‐5 questionnaire Time points measured: start, 1 month and 2 months of the study Time points reported: start, 1 month and 2 months of the study Subgroups: no Adverse events How measured: Narratively
Funding sources	Grant of Dankook University
Declarations of interest	Not reported
Notes	Language of publication: Korean Email: killtumor@yahoo.co.kr
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	Single‐blinded: No information available.. We wrote to study authors
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	Single‐blinded: No information available. We wrote to study authors
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	No information available. We wrote to study authors
Selective reporting (reporting bias)	Unclear risk	Protocol not available.. We wrote to study authors
Other bias	Low risk	No other sources of bias detected

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Shi 1994.

Methods	Study design: Parallel‐group randomised trial Study dates: in 1994, exact dates not mentioned Setting: outpatient ‐ may be single centre ‐ national Country: China
Participants	Inclusion criteria: Not mentioned. According to the paper, participants included should at least be nonbacterial prostatitis Exclusion criteria: Not mentioned Sample size: 60 participants Age (years): not reported Baseline NIH‐CPSI score: not available. All participants were men
Interventions	Group 1 (n = 30): QianLieAnWan was administered orally 2 ˜ 3 times a day, 9 g each time for 30 days Group 2 (n = 30): QianLieKang tablet was administered regularly combined with thermotherapy for 30 days Co‐interventions: Not mentioned
Outcomes	There was no report of outcomes relevant to this review
Funding sources	Not mentioned
Declarations of interest	Not mentioned
Notes	A combination of subjective clinical parameters alongside laboratory findings formed a composite outcome (not relevant for our review). This study was written in Chinese. No contact information available
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “patients were randomly assigned to two groups”(in Chinese) Comment: the method for randomisation is not mentioned
Allocation concealment (selection bias)	Unclear risk	Allocation concealment is not described
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Blinding of participants and personnel is not described. However, considering the visible difference between the 2 interventions (with or without massage), blinding was unlikely
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Blinding of participants and personnel is not described. However, considering the visible difference between the two interventions (with or without massage), blinding was unlikely.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data were available for al participants
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias were detected

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Shoskes 1999.

Methods	Study design: Parallel‐group randomised trial Study dates: study dates not available Setting: outpatient ‐ single centre ‐ national Country: USA
Participants	Inclusion criteria: participants with CPPS for at least 6 months (they might not have met the 1999 consensus criteria for CP/CPPS) Exclusion criteria: positive culture in urine, prostatic secretion, urethral swab, first voided and midstream urine Sample size: 30 Age (years): Group 1 mean = 43.5 (SD 3.7); Group 2 mean = 46.2 (SD 4) NIH‐CPSI baseline score: Group 1 mean = 20.2 (SD 1.1); Group 2 mean = 21.0 (SD 1.8) All participants were men
Interventions	Group 1 (n = 15): quercetin capsules 500 mg orally twice daily for 1 month Group 2 (n = 15): placebo capsules orally twice daily for 1 month Co‐interventions: not available
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline and 1 month Time points reported: baseline and 1 month Adverse Events How measured: Narratively
Funding sources	No information available.
Declarations of interest	Quote: “D. A. Shoskes and J. Rajfer own stock in companies that will benefit from sales of the supplements reported in this study.”
Notes	A second open‐label period was continued with 17 participants, these results were not included in this review due to insufficiencies in the report. No contact information available
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “Patients were randomized 1:1 in a double‐blind fashion” Comment: no other information available
Allocation concealment (selection bias)	Unclear risk	Quote: “Patients were randomized 1:1 in a double‐blind fashion” Comment: no other information available
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	Quote: “Patients were randomized 1:1 in a double‐blind fashion” Comment: it is not clear if personnel were blinded
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Quote: “Patients were randomized 1:1 in a double‐blind fashion” and “Both quercetin and placebo capsules were identical in appearance.”
Incomplete outcome data (attrition bias)   All outcomes	High risk	All outcomes: 2/15 participants in the placebo group left due to worsening symptoms (no outcome data)
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias were identified

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Singh 2017.

Methods	Study design: Parallel‐group randomised trial Study dates: study dates not available Setting: outpatient ‐ single centre ‐ national Country: India
Participants	Inclusion criteria: men diagnosed with chronic prostatitis or chronic pelvic pain syndrome, aged 15 to 65 years Exclusion criteria: not available Sample size: 68 participants randomised Age (years): not available NIH‐CPSI baseline score: not available All participants were men
Interventions	Group 1 (n = 36): tadalafil 5 mg in once‐daily dose for 6 weeks plus standard medical therapy Group 2 (n = 32): standard medical therapy Co‐interventions: standard medical therapy comprised: levofloxacin 500 mg for 6 weeks and alfuzosin 10 mg for 6 weeks
Outcomes	Prostatitis symptoms How measured: NIH‐CPSI score Time points measured: baseline, 6 weeks Time points reported: 6 weeks (change from baseline with P value) Urinary symptoms How measured: IPSS score Time points measured: baseline, 6 weeks Time points reported: 6 weeks (change from baseline with P value) Sexual dysfunction How measured: baseline, IIEF score Time points measured: baseline, 6 weeks Time points reported: 6 weeks (change from baseline with P value) Adverse events How measured: narratively, reported by the author in personal communication
Funding sources	None
Declarations of interest	Not available
Notes	The information was combined from an abstract from a medical conference and the clinical trial registry (CTRI/2016/08/007208). We wrote to study authors to complete the missing information: shuki_79@yahoo.co.in. The author replied with additional information
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Author replied that it was generated by a computer
Allocation concealment (selection bias)	Low risk	Author replied that it was a central allocation
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Author replied that the study was not blinded
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Author replied that the study was not blinded
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: author replied that there was a "5‐10% fall out"
Selective reporting (reporting bias)	Unclear risk	No information available (abstract only)
Other bias	Unclear risk	No information available (abstract only)

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Sivkov 2005.

Methods	Study design: Parallel‐group randomised trial Study dates: study dates not available Setting: outpatient Country: Russia
Participants	Inclusion criteria: men with a diagnosis of CP/CPPS (type IIIa) for 2 years and more; age 25 ‐ 45; absence of urinary/reproductive tract infections; altered prostate secretion which is commonly found in CP/CPPS cases; symptoms of CP/CPPS Exclusion criteria: not specified Sample size: 64 patients were randomised Age (years): not reported NIH‐CPSI baseline total score: Group 1 mean = 25.66 (SD 6.55); Group 2 mean = 25.73 (SD 4.97) All participants were men
Interventions	Group 1 (n = 29): terazosin orally, gradually increasing from 1 to 5 mg/day for 2 weeks, and then 8 weeks of 5 mg/day terazosin Group 2 (n = 22): placebo orally, imitation of the gradual increase of the active drug for 2 weeks, and then 8 weeks of placebo
Outcomes	Prostatitis Symptoms How measured: NIH‐total score and pain, urinary, and QoL domains Time points measured: baseline, 12 months Time points reported: baseline, 12 months Adverse events How measured: narratively
Funding sources	None
Declarations of interest	None
Notes	Prior to randomisation, all recruited volunteers (n = 64) were treated with placebo for 2 weeks to identify placebo responses. So in total 64 participants entered the study, but the follow‐up was documented for 29 and 22 men in active treatment group and placebo group, respectively. No contact information available
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information provided other than "patients were randomized into 2 groups.." statement
Allocation concealment (selection bias)	Unclear risk	No information available
Blinding of participants and personnel (performance bias)   Subjective outcomes	Low risk	The packaging for the 2 alternative treatments was identical with exception of labels A1 and A2 (for active treatment)/ B1 and B2 (for placebo). Neither participants nor investigators were aware about the labelling
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	The packaging for the 2 alternative treatment was identical with exception of labels A1 and A2 (for active treatment)/ B1 and B2 (for placebo). Neither patients nor investigators were aware about the labelling
Incomplete outcome data (attrition bias)   All outcomes	High risk	All outcomes: missing outcome data in 3/29 from active group vs 10/22 from placebo group
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Unclear risk	Some of baseline parameters (age, duration of symptoms) were not reported

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Sun 2008.

Methods	Study design: Parallel‐group randomised trial Study dates: start date May 2007 ‐ end date February 2008 Setting: Outpatient ‐ possibly single centre ‐ national Country: China
Participants	Inclusion criteria: men aged 18 to 55 years old with symptoms of chronic prostatitis, such as frequent urination, discomfort urination, or perineal pain or discomfort, which lasted for at least 4 weeks, WBC/EPS ≥ 10/HP, decreased counting or disappearance of lecithin bodies, bacteria culture negative; routine urine analysis normal. Patients who did not take any other medication for chronic prostatitis or drugs that interfere with urination Exclusion criteria: Acute prostatitis, benign hyperplasia of the prostate, prostate cancer, neurogenic bladder, urethral malformation or narrowing or serious neurosis, stones of the ureter or bladder, inguinal hernia, inflammation of the ulna, varicocoele, epididymitis, or diseases of the colon or rectum, serious primary diseases of the heart, brain, liver and haemopoietic system, patients with “allergic constitution” or allergic to multiple drugs, patients who could not co‐operate, say, patients with mental disorders, patients who had any of the following conditions which could influence the effectiveness of treatment or the assessment of safety: (1) patients who did not meet the inclusion criteria; (2) patients who did not take medications as instructed; (3) patients whose effectiveness of treatment could not be assessed, or whose information is incomplete Sample size: 115 participants Age (years): Overall: 19 ˜ 47, Mean: 31.6 NIH‐CPSI baseline total score: Group 1 = 24.46 (SD 5.38); Group 2 = 23.51 (SD 4.86) All participants were men
Interventions	Group 1 (n = 73): QianLieAnTong tablet (0.38 g per tablet), by mouth 3 times a day, 4 tablets each time for 1 month Group 2 (n = 42): Only co‐interventions Co‐interventions: Terazosin hydrochloride tablet (2 mg per tablet), by mouth once a day, 1 tablet each time; taking the tablet before going to bed No other medications or physical therapies allowed during the trial
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI global and subscore Time points measured: before treatment, after treatment Time points reported: before treatment, after treatment Subgroups: none Adverse Events How measured: Narratively
Funding sources	Not mentioned
Declarations of interest	Not mentioned
Notes	This study was written in Chinese No contact information available.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “we conducted a randomized controlled clinical trial”. Comment: However, the method for randomisation is not described
Allocation concealment (selection bias)	Unclear risk	Allocation concealment is not described
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Blinding of participants and personnel is not described. However, considering the visible differences between the two interventions, blinding cannot be achieved
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Blinding of outcome assessment is not described. Self‐reported outcomes, participants are not blinded
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data were available for all participants
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias were detected

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Tan 2009.

Methods	Study design: Parallel‐group randomised trial Study dates: start date March 2006 ‐ end date December 2006 Setting: outpatient ‐ possibly single centre ‐ national Country: China
Participants	Inclusion criteria: men aged 20 to 50 years old, with a course of disease > 3 months, diagnosed with type III chronic prostatitis according to NIH‐1999 criteria and volunteered to participate in this clinical trial Exclusion criteria: type I, II or IV prostatitis, patients with haemorrhoids, anal fissure, anal fistula or other anorectal diseases. Patients with diseases of the urinary system, such as hyperplasia of the prostate, prostate cancer, epididymitis, gonorrhoea, etc. Patients who could not tolerate the medications for this trial Sample size: 90 participants Age (years): Group 1: Trial group: 33.56 ± 8.43; Group 2: Control group: 33.00 ± 8.46 NIH‐CPSI baseline total score: Group 1 = 24.53 (SD 4.90); Group 2 = 25.07 (SD 4.19) All participants were men
Interventions	Group 1 (n = 45): Tamsulosin tablet 0.2 mg, by mouth once a day; take the medication before going to bed. QianLie AnShuan (Prostat) 2 g once a day; participants took the lateral position and inserted the drug into the anus for about 3 ˜ 4 cm after stool each night before going to bed Group 2 (n = 43): Terazosin 2 mg by mouth once a day, take the medication before going to bed Co‐interventions: Duration of treatment: 6 weeks. Avoid alcohol and staying up late during the trial. A regular lifestyle is recommended during the trial
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI global and subscore Time points measured: before treatment, after treatment Time points reported: before treatment, after treatment Subgroups: none Adverse Events How measured: Narratively
Funding sources	Not mentioned
Declarations of interest	Not mentioned
Notes	This study was written in Chinese No contact information available
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “starting from a particular row, the numbers on a random sequence chart were assigned to the patients according to the date of admission. If the number was odd then patient was assigned to the trial group, if even then control group”
Allocation concealment (selection bias)	Unclear risk	Allocation concealment is not described
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Blinding of participants and personnel is not described. However, considering the visible differences between the 2 interventions, blinding cannot be achieved
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Blinding of outcome assessment is not described. Self‐reported outcomes, participants are not blinded
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Missing outcome (all outcomes) data: Quote: “2 patients of the control group dropped out because of intolerable adverse effects and drug withdrawal” (2/45 = 4.4% of attrition)
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias were detected

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Tugcu 2006.

Methods	Study design: Parallel‐group randomised trial Study dates: January 2003 ‐ February 2004 Setting: Hospital outpatient ‐ multicentre Country: Turkey
Participants	Inclusion criteria: Type IIIB chronic prostatitis; NIH CPSI scores in articles 1. and 2. to be 1 or higher, and score in article 9 to be 4 or higher; symptoms for longer than 3 months Exclusion criteria: Diagnosed as chronic bacterial prostatitis by lower urinary system localisation test, history of urinary tract infection within last year, having important medical problems, having any of the NIH consensus exclusion criteria and history of treatment with alpha blockers Sample size: 45 Age (years): 34.1 ± 8.39 years. Groups : No group mean ages were reported NIH‐CPSI baseline total score: not available All participants were men
Interventions	Group 1 (n = 23): Thiocolchicoside 120 mg/day and ibuprofen 1200 mg/day. For 6 months. Possibly oral, once a day Group 2 (n = 22): Only co‐intervention Co‐interventions: Both groups received terazosin 5 mg a day
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI subscores Time points measured: Pre‐treatment, end of treatment and 6 months after the end of treatment Time points reported: Pre‐treatment, end of treatment and 6 months after the end of treatment
Funding sources	Not reported
Declarations of interest	Not reported
Notes	Dose of thiocolchicoside seems high, since it usually ranges from 8 to 16 mg a day, but this was extracted textually from the report Email: cekmd@doruk.net.tr
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Open‐label study
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Open‐label study
Incomplete outcome data (attrition bias)   All outcomes	High risk	Outcome data were not available for 6 participants, who were excluded from the study because of the side effects of the drug (hypotension 3 participants, gastric complaints 3 participants)
Selective reporting (reporting bias)	Unclear risk	Total NIH‐CPSI score not reported. No protocol available. We wrote to study authors
Other bias	Unclear risk	Participants' baseline characteristics were not described

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Turkington 2002.

Methods	Study design: Parallel‐group randomised trial Study dates: "study dates not available" Setting: outpatient ‐ single centre ‐ national Country: UK
Participants	Inclusion criteria: male participants aged 18 or older, with perigenital pain of > 1 year, absence of local or systemic inflammation or infection Exclusion criteria: the presence of kidney or bladder stones, urethral stricture or bladder pathology, abnormal ultrasound; neuropsychiatric illness, suicide risk, previous treatment with fluvoxamine and current treatment with antidepressants Sample size: 42 participants were randomised Age (years): median age 41 (range 18 ‐ 72) NIH‐CPSI baseline score: not available. All participants were men
Interventions	Group 1 (n = 21): fluvoxamine 50 mg daily for 8 weeks Group 2 (n = 21): matching placebo tablets of the same posology Co‐interventions: dose was duplicated in both arms if there was no improvement in symptoms. Compliance was checked
Outcomes	Anxiety and depression How measured: Montgomery‐Asberg Depression Rating Scale, Hamilton Rating Scale for Anxiety, Hospital Anxiety and Depression Scale, General Health Questionnaire Time points measured: baseline and 8 weeks Time points reported: baseline and 8 weeks Adverse events How measured: Narratively
Funding sources	Supported by a grant from Solvay/Duphar, Southampton, UK
Declarations of interest	Dr. Rao has received honoraria from Lilly, Organon, Pfizer and Lundbeck
Notes	Prostatitis symptoms were not assessed. A pain score was used as an outcome Email: douglas.turkington@ncl.ac.uk
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation
Allocation concealment (selection bias)	Unclear risk	Quote: “allocated in a double‐blind design”. Comment: No other information available. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	Double‐blind. Not specified if study personnel were blinded. We wrote to study authors
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Participants were blinded using placebo
Incomplete outcome data (attrition bias)   All outcomes	High risk	All outcomes: outcome data were not available in 8/21 and 5/21 participants in each group, due to adverse events
Selective reporting (reporting bias)	Unclear risk	No protocol available. We wrote to study authors
Other bias	Low risk	No other sources of bias were identified

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Tuğcu 2007.

Methods	Study design: Parallel‐group randomised trial Study dates: start date September 2004 ‐ end date December 2005 Setting: outpatient ‐ possible single centre ‐ national Country: Turkey
Participants	Inclusion criteria: a diagnosis of Category IIIB CPPS, aged 20 – 45 years old, with a NIH‐CPSI score of > 1 on items 1 and 2 (pain and discomfort); a score of > 4 on item 9 (quality of life), symptoms for > 3 months and a desire to be treated Exclusion criteria: criteria for chronic bacterial prostatitis, Category IIIA CPPS, history of a previous urinary tract infection or a uropathogen documented within the last year, those with significant medical problems, NIH consensus exclusion criteria and those who had been treated or were taking medications that could affect lower urinary tract function Sample size: 90 participants randomised Age (years): overall mean 29.1 (SD 5.2) NIH‐CPSI baseline score: Group 1 mean = 23.1 (SD 1.8); Group 2 = 21.9 (SD 1.5); Group 3 mean = 22.9 (SD 1.2) All participants were men
Interventions	Group 1 (n = 30): only co‐interventions Group 2 (n = 30): ibuprofen 400 mg and thiocolchicoside 12 mg daily for 6 months + co‐interventions Group 3 (n = 30): 1 placebo tablet a day for 6 months Co‐interventions: Both groups 1 and 2 received doxazosin 4 mg a day
Outcomes	Prostatitis symptoms How measured: NIH‐CPSI score Time points measured: baseline, 6 and 12 months Time points reported: baseline, 6 and 12 months Adverse events How measured: Narratively
Funding sources	Not available
Declarations of interest	Not available
Notes	We wrote to study author. We received a response through our Turkish collaborator (see Acknowledgements) Email: cekmd@doruk.net.tr.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “were randomised into three groups in order of appearance” Comment: no additional information available. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	Quote: “were randomised into three groups in order of appearance” Comment: no additional information available. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Quote: “Placebo tablets compounded of lactose had a similar, appearance to doxazosin tablets. Ibuprofen was given at a low dose, with an effort to avoid side‐effects during the long period of treatment”; Comment: the interventions in group 1 and 2 were visibly different. No information on blinding of personnel. Author stated that there was no blinding (personal communication)
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	The interventions in group 1 and 2 were visibly different. No information on blinding of participants. Author stated that there was no blinding (personal communication)
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Quote: “Eighty‐three of the initial 90 patients were eligible for evaluation after 6 mo, and 79 patients were eligible at the end of 12 mo”, then the author states that at 6 months 1, 1 and 2 participants had dropped out in each study arm. It is unclear how many participants were evaluated at each time point and study arm. We wrote to study authors
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias were identified

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Wagenlehner 2009.

Methods	Study design: Parallel‐group randomised trial Study dates: start date December 1999 ‐ end date January 2004 Setting: Outpatient ‐ multicentre ‐ national Country: Germany
Participants	Inclusion criteria: men aged 18 ‐ 65 with symptoms of pelvic pain for at least 3 months during the 6 months before the trial; pain domain score of NIH‐CPSI ≥ 7; leukocytes of ≥10 in VB3 (field of vision: x 400) Exclusion criteria: Quote: “(1) urinary tract infection; (2) acute bacterial or chronic bacterial prostatitis at study entry (bacteriuria ≥104 colony‐forming units (CFU)/ml in mid‐stream urine (VB2) or ≥103 CFU/ml in VB3); (3) history of urethritis, with discharge 4 week prior to study entry; (4) a history of epididymitis or sexually transmitted disease (STD); (5) residual urine volume >50 ml resulting from bladder outlet obstruction (BOO); (6) indication for or history of prostate surgery, including prostate biopsy; (7) history of urogenital cancer; (8) treatment with phytotherapeutic agents, a‐blocker agents, or antimicrobial substances with prostatic penetration 4 wk prior to study entry; (9) treatment with agents influencing intraprostatic hormone metabolism 6 months prior to study entry.” Sample size: 139 participants Age (years): Group Pollen extract: mean age = 39.7 ± 7.2 Group Placebo: mean age = 39.3 ± 9.1 Baseline NIH‐CPSI score: Group 1 = 19.3 (SD 5.1); Group 2 = 20.3 (SD 5.2) All participants were men
Interventions	Group 1 Pollen extract (n = 70): "two capsules every 8 hours, with the active substance consisting of 60 mg Cernitin T60 (water soluble fraction) and 3 mg Cernitin GBX (fat soluble fraction)" Duration: 12 weeks Group 2 Placebo (n = 69): “two capsules every 8 hours, with identical capsulation and weight only containing the inactive substances in proportional doses as compared with the pollen extract". Duration: 12 weeks Co‐interventions: Patients included in the screening phase were pre‐treated with azithromycin (250 mg every 6 hours for 1 day) to eliminate atypical pathogens
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI total score and subscores in pain, micturition, and quality of life domains Time points measured: baseline, 6,and 12 weeks Time points reported: baseline, 6, and 12 weeks Urinary symptoms How measured: International Prostate Symptom Score (IPSS) Time points measured: baseline, 6, and 12 weeks Time points reported: baseline, 6, and 12 weeks Adverse events How measured: Narratively
Funding sources	Quote: “This study was supported by an unrestricted grant by Strathmann AG&Co”
Declarations of interest	“None”
Notes	Sexual dysfunction was collected but not in a validated scale We contacted Dr. Wagenlehner for clarification but the author replied that he no longer has the study data
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “Randomisation was carried out in blocks (n = 4) within the centre using a random number generator.”
Allocation concealment (selection bias)	Low risk	Quote: “The investigators were instructed to use the study drug in ascendant order of random numbers available in the respective trial centre.”
Blinding of participants and personnel (performance bias)   Subjective outcomes	Low risk	Double‐blind study. Using “identical capsulation and weight” capsules
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Double‐blind study. Using “identical capsulation and weight” capsules
Incomplete outcome data (attrition bias)   All outcomes	High risk	Missing outcome data (all outcomes) Post‐randomisation exclusion of 9 patients due "to wrong allocation" and 12 participants due to outcome data not being available (no treatment arm specified)
Selective reporting (reporting bias)	High risk	Clinical trial record specified outcome measurements at week 6 (presented only graphically)
Other bias	High risk	The pharmaceutical company participated in the conduct of the study: Quote: “These sponsors contributed to the design and conduct of the study as well as data collection.” Additionally, there were post‐randomisation exclusions for “wrong allocation”. This could indicate that there were problems in the allocation concealment. We requested further explanations from the authors, but they no longer had the data set

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Wagenlehner 2014.

Methods	Study design: Parallel‐group randomised trial Study dates: start date July 2008 ‐ end date December 2010 Setting: outpatient ‐ multicentre ‐ international Country: Austria, Germany, Poland, Portugal
Participants	Inclusion criteria: Men aged 30 to ≤ 60 years, presenting CP/CPPS (type II or type III): pain or discomfort in the pelvic region for at least 3 months in the previous 6 months; corresponding symptoms could be perineal, lower abdominal, testicular and/or penile, rectal and lower back, or suprapubic, and might be associated with ejaculatory discomfort or voiding (associated voiding symptoms are irritative or obstructive in nature, similar to symptoms associated with benign prostatic hyperplasia); with a total NIH‐CPSI ≥ 15; having signed a written informed consent Exclusion criteria: Consensus NIH criteria: 1. Any prostate, bladder, or urethral cancer, seizure disorder 2. Presence of a concurrent inflammatory bowel disease, disorder affecting the bladder, liver disease 3. Prior 12 months diagnosed with or treated for symptomatic genital herpes 4. Prior 3 months Urinary Tract Infection, with a urine culture value of >100,000 CFU/mL; clinical evidence of urethritis, sexually transmitted diseases, symptoms of acute or chronic epididymitis 5. Any pelvic radiation, systemic chemotherapy; intravesical chemotherapy; intravesical BCG, TURP, TUIP, TUIBN, TUMT, TUNA, any other prostate surgery or treatment such as cryotherapy or thermal therapy; prior treatment for orchialgia without pelvic symptoms to treatment 6. Prior 3 months prostate biopsy 7. Treatment by the following concomitant medication: immunosuppressive medication, e.g. systemic corticosteroids (>15 mg prednisolone); methotrexate; any other immunostimulant medication or live vaccine 8. Prior 6‐month treatment by the following medication: initiated or stopped finasteride or other androgen hormone inhibitors 9. Prior 4‐week treatment by the following medication: immunosuppressive medication or immunostimulant medication or live vaccine; antimicrobial agents (oral or parenteral); started, stopped, or changed dose level of any prostatitis‐specific medications 10. Prior 2‐week treatment by bioflavonoid agents, zinc or iron supplements 11. Inability to comply with the requirements of the protocol (e.g. psychiatric problems; knowledge of language, unable to complete a patient diary, etc...) 12. Known allergy or previous intolerance or known hypersensitivity to the trial drug 13. Participation in another clinical trial and/or treatment with an experimental drug within 3 months before study start and during the present trial Sample size: 185 participants randomised Age (years): Group 1 mean = 47.8 (SD 8.7); Group 2 mean = 47.6 (SD 8.1) NIH‐CPSI baseline score: Group 1 mean = 21.8 (SD 3.8); Group 2 mean = 23.0 (SD 5.6) All participants were men
Interventions	Group 1 (n = 94): OM‐89 (OM Pharma SA., Geneva, Switzerland) containing 6 mg of E. coli lysate from 18 strains; 1 capsule daily for 3 months, then 3 months without treatment, followed by 1 capsule daily for 10 days a month for 3 months Group 2 (n = 91): Same posology of placebo (matched capsule) Co‐interventions: other medications were allowed in both groups (alpha blockers, antibiotics, analgesics, relaxants, sedatives, etc.)
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline, 3, 9, 12 months Time points reported: baseline, 3, 9, 12 months Adverse Events How measured: Narratively
Funding sources	Quote: “The study was supported by Vifor Pharma/OM Pharma SA, Geneva. Data management and statistical analysis were performed by ICTA, Fontaines‐les‐Dijon (France), a contract research organization.”
Declarations of interest	Quote: “Florian M.E. Wagenlehner has served as a paid consultant for Astellas, AstraZeneca, Bionorica, Cernelle, Cubist, OM‐Pharma, Lilly Pharma, Pierre Fabre, Rosen‐Pharma. He has received lecture honoraria from AstraZeneca, Bionorica, OM‐Pharma, Pierre Fabre, Rosen Pharma, Serag Wiessner, Zambon. He has been paid for performing clinical trials on behalf of Astellas, AstraZeneca, Calixa, Cerexa, Cernelle, Cubist, GSK, Merlion, OM‐Pharma, Janssen‐Cilag, Johnson & Johnson, Lilly Pharma, Pharmacia, Pierre‐Fabre, Rosen Pharma, Sanofi‐Aventis, Strathmann, Zambon. Stefania Ballarini is a Vifor Pharma/OM Pharma Global Medical Affairs employee. Kurt G. Naber has served as paid consultant for Basilea, Bionorica, Cubist, Galenus, MerLion, OM Pharma/Vifor, Paratek, Pierre Fabre, Rempex, Rosen Pharma, Zambon. He has received lecture honoraria from Angelini, Daiichi Sankyo, OM Pharma/Vifor, Pierre Fabre, Zambon. He has been paid for performing clinical trials on behalf of Basilea, Bionorica, MerLion, OM Pharma/Vifor, Rosen Pharma, Zambon.”
Notes	Clinical Trial registry: EudraCT number: 2007‐004609‐85 Contact information: Wagenlehner@aol.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	No information available in the paper but the author described random blocks in personal communication
Allocation concealment (selection bias)	Low risk	No information available in the paper but the author described concealed allocation in personal communication
Blinding of participants and personnel (performance bias)   Subjective outcomes	Low risk	Participants were blinded with the use of placebo. No information about study personnel in the paper, but the author described blinding of personnel in personal communication
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Participants were blinded with the use of placebo
Incomplete outcome data (attrition bias)   All outcomes	High risk	At 3 months follow‐up outcome data (prostatitis symptoms) were available for 87/94 (active treatment) and 79/91 (placebo) participants, at 12 months, 81/94 (active treatment) and 73/91 (placebo). Unbalanced attrition For adverse events outcome data were available for all participants (low risk of bias) at complete follow‐up
Selective reporting (reporting bias)	Low risk	All outcomes planned in the clinical trial registry were reported
Other bias	Low risk	No other sources of bias were identified

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Wang 2004.

Methods	Study design: Parallel‐group randomised trial Study dates: start date September 2002 ‐ end date March 2003 Setting: outpatient ‐ single centre ‐ national Country: China
Participants	Inclusion criteria: According to Nickel 1998. NIH‐CPSI > 8 Exclusion criteria: According to Nickel 1998. Sample size: 38 participants Age (years): Overall 20 ˜ 48; mean 28 Baseline NIH‐CPSI score: not available. All participants were men
Interventions	Group 1 (n = 24): 6 mL of mixed solution of Chuanshentong (4 mL) and 2% lidocaine (2 mL) was trans‐perineally injected into one lobe of the prostate, once a day for 6 days Group 2 (n = 14): 6 mL of lidocaine and saline solution was trans‐perineally injected into one lobe of the prostate, once a day for 6 days Co‐interventions: not available.
Outcomes	Prostatitis Symptoms How measured: changes in NIH‐CPSI Time points measured: before treatment, Week 4 ‐ 12 Time points reported: Week 4, Week 6 Subgroups: none Adverse Events How measured: Narratively
Funding sources	Not mentioned
Declarations of interest	Not mentioned
Notes	This study was written in Chinese Email: urology@sohu.com (email bounced)
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote:“Patient s were randomly divided into 2 groups…”, Comment: the exact method for randomisation is unknown. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	Allocation concealment is not described. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Patients were not blinded
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Blinding of outcome assessment is not described. Self‐reported outcomes, participants are not blinded
Incomplete outcome data (attrition bias)   All outcomes	Low risk	1 participant in trial group (1/24 = 4.2%) and 1 participant in control group (1/14 = 7.1%) lost follow‐up at week 3
Selective reporting (reporting bias)	High risk	It seemed that the authors had follow‐up data from Week 4 to Week 12, but only those of Week 4 and Week 6 were reported
Other bias	Low risk	No other sources of bias were detected

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Wang 2016.

Methods	Study design: Parallel‐group randomised trial Study dates: start date January 2011 ‐ end date January 2014 Setting: outpatient ‐ possible single centre ‐ national Country: China
Participants	Inclusion criteria: men suffering from urinary symptoms (frequent urination, dribbling urine sense) and pain or discomfort in the perineum, testicles, and lumbosacral region for over 3 months with negative results of urinary and prostatic secretions culture and no history of treatment with antibiotics and alpha receptor blocker Exclusion criteria: a history of urinary tract infection, benign prostatic hyperplasia and other pelvic organic diseases Sample size: 115 randomised Age (years): Group 1 mean = 36.6 (SD 8.1); Group 2 mean = 38.5 (SD 8.3); Group 3 mean = 37.8 (SD 7.9) NIH‐CPSI baseline score: Group 1 mean = 24.2 (SD 7.1); Group 2 = 22.3 (SD 6.6); Group 3 = 22.6 (SD 6.8) All participants were men
Interventions	Group 1 (n = 38): levofloxacin 200 mg twice daily for 6 weeks Group 2 (n = 38): terazosin 2 mg once daily for 6 weeks Group 3 (n = 39): levofloxacin 200 mg twice daily and terazosin 2 mg once daily for 6 weeks Co‐interventions: All participants received dietary advice (to avoid spicy food and alcohol consumption, increase water intake), received prostatic massage once a week and were advised to take warm baths
Outcomes	Prostatitis symptoms How measured: NIH‐CPSI score Time points measured: baseline and 6 weeks Time points reported: baseline and 6 weeks Sexual Dysfunction How measured: IIEF‐5 Time points measured: baseline and 6 weeks Time points reported: baseline and 6 weeks Adverse Events How measured: Narratively
Funding sources	None
Declarations of interest	None
Notes	Clinical Trial Registry: ChiCTR‐IPR‐15006189 This study was written in Chinese Email: Zhonghua Xu zg9800@163.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random blocks
Allocation concealment (selection bias)	Unclear risk	No information available
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Open‐label study
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Open‐label study
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data were available for all participants
Selective reporting (reporting bias)	Low risk	Predefined outcomes were reported (Clinical Trial Registry)
Other bias	Low risk	No other sources of bias were identified

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Wedren 1987.

Methods	Study design: Parallel‐group randomised trial Study dates: start date October 1984 ‐ end date February 1985 Setting: outpatient ‐ single centre ‐ national Country: Sweden
Participants	Inclusion criteria: score with typical history > 9, score of signs and symptoms > 9, age between 20 and 50 years old, normal blood testing, no earlier isolation of bacteria in prostate secretion and urine and informed consent Exclusion criteria: other diseases except Reiter syndrome and ankylosing spondylitis (for their relationship with prostatitis), receiving other medication during the study period Sample size: 30 participants randomised Age (years): Group 1 mean = 37.3; Group 2 mean = 37.9 NIH‐CPSI baseline score: Not available All participants were men
Interventions	Group 1 (n = 15): Elmiron® (Pentosan polysulphate) 100 mg, 2 capsules twice daily for 3 months Group 2 (n = 15): Placebo with the same posology for 3 months Co‐interventions: not available
Outcomes	Adverse events How measured: Narratively
Funding sources	Not available
Declarations of interest	Not available
Notes	The study included several outcomes on clinical improvement, but it was not measured on any validated scale. No contact information available
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available
Allocation concealment (selection bias)	Unclear risk	No information available
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	The study is described as “double blind”, but it is not clear who was blinded (it is not clear whether personnel were blinded)
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Quote: “the study is described as double blind” There was use of identical placebo
Incomplete outcome data (attrition bias)   All outcomes	High risk	3 participants (2 in Pentosan and 1 in placebo) were excluded due to the presence of E. coli in the culture. 1 participant stopped treatment in the pentosan group due to adverse events. 2 participants in the Pentosan group were excluded because they decided to use antibiotics. In total, 5 participants dropped out in the Pentosan group and 1 in the placebo group
Selective reporting (reporting bias)	Unclear risk	Protocol not available
Other bias	Low risk	No other sources of bias were identified

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Wu 2008.

Methods	Study design: Parallel‐group randomised trial Study dates: start date January 2006 ‐ end date December 2007 Setting: outpatient ‐ single centre ‐ national Country: China
Participants	Inclusion criteria: (not specified clearly, drawn from participant’s characteristics) Diagnostic criteria: with reference to NIH standard (J Urol 2004) and Chinese standard (2007) [Refs 1,5]. Age 20 ˜ 50, first and second score of NIH‐CPSI > 1, course of disease > 3 months and patients actively sought medical treatment. Patients did not receive any treatment before admission, did not take any alpha blockers or cyclo‐oxygenase inhibitors. In an effort to exclude chronic bacterial prostatitis, all patients undertook routine urine test, urine culture, EPS routine test and EPS culture before and after prostate massage Exclusion criteria: Patients who received analgesics, had a history of acute urinary infection, had serious cardiovascular or cerebrovascular diseases, or were allergic to alpha blockers or cyclo‐oxygenase inhibitors Sample size: 123 participants Age (years): Group 1: doxazosin group: 34.5 ± 8.5; Group 2: diclofenac group: 35.0 ± 8.8; Group 3: combination group: 34.9 ± 8.4 Baseline NIH‐CPSI score: Group 1 = 24.1 ± 2.2; Group 2 = 23.95 ± 2.17; Group 3 = 23.82 ± 1.72 All participants were men
Interventions	Group 1 (n = 43): Doxazosin 4 mg by mouth once a day for 12 weeks Group 2 (n = 39 ): Diclofenac 75 mg by mouth once a day for 12 weeks Group 3 (n = 41): Doxazosin 4 mg by mouth once a day + diclofenac 75 mg by mouth once a day for 12 weeks Co‐interventions: no information
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI global and subscore Time points measured: before treatment, after treatment Time points reported: before treatment, after treatment Subgroups: none Adverse Events How measured: Narratively
Funding sources	Not mentioned
Declarations of interest	Not mentioned
Notes	This study was written in Chinese E‐mail: xsj@citiz.net
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “123 patients were randomly divided into 3 groups”. Comment: However, the exact method for randomisation is unknown. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	Allocation concealment is not described. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Blinding of participants and personnel is not described. However, considering the visible differences between the interventions (single drug versus combination), blinding cannot be achieved
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Blinding of outcome assessment is not described. Self‐reported outcomes, participants are not blinded
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: “8 patients lost follow‐up and the attrition is 6.5%”, and “3 of them lost follow‐up because they did not have adequate time for the treatment; the other 5 of them lost follow‐up for unknown reason”
Selective reporting (reporting bias)	Unclear risk	No protocol available. We wrote to study authors
Other bias	Low risk	No other sources of bias were detected

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Xia 2014.

Methods	Study design: Parallel‐group randomised trial Study dates: start date November 2011 ‐ start date November 2012 Setting: outpatient ‐ possibly single centre ‐ national Country: China
Participants	Inclusion criteria: Age > 18; Course of disease > 3 months; NIH‐CPSI > 15; The article reported that the participants included were already diagnosed with type III CP/CPPS Exclusion criteria: Patients who had a history of infection of the urinary system within 3 months; patients with history of tumour of the urinary system or the rectum; patients with diseases of the nervous system; patients with narrowing of the urinary tract or history of transurethral surgery; patients with acute diseases or other diseases which needed treatment; Age > 55 Sample size: 88 participants Age (years, mean, SD): Group 1: experimental group 33.88 ± 5.68; Group 2: control group 34.54 ± 6.45. Baseline NIH‐CPSi score: Group 1 = 28.32 ± 4.90; Group 2 = 28.54 ± 5.03 All participants were men
Interventions	Group 1 (n = 44): Usual care (see Co‐interventions) + YuLeShu Oral Mixture 3 times a day, 20 mL each time Group 2 (n = 44): Usual care only (see co‐interventions) Co‐interventions: Common clinical practice for CP/CPPS in that setting, which includes: Anaibiotics: levofloxacin tablet 0.2 g twice a day, course of treatment is 4 weeks; alpha blockers: doxazosin hydrochloride tablet 2 mg once a day, course of treatment is 4 weeks; Chinese patent medicine: QianLieTongYu capsule 3 times a day, 4 capsules each time, course of treatment is 4 weeks; prostate massage: once a week Duration: 1 course of treatment (total: 4 weeks)
Outcomes	Prostatitis symptoms How measured: NIH‐CPSI global and pain subscore Time points measured: before treatment, after treatment Time points reported: before treatment, after treatment Subgroups: none Sexual Dysfunction How measured: IIEF‐5 Time points measured: before treatment, after treatment Time points reported: before treatment, after treatment Subgroups: none Anxiety and depression How measured: HAM‐D, HAM‐A Time points measured: before treatment, after treatment Time points reported: before treatment, after treatment Subgroups: none
Funding sources	Not mentioned
Declarations of interest	Not mentioned
Notes	This study was written in Chinese Email: flyman880@163.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	The paper reported that the randomisation was achieved by using computer, but it is unclear what software was used and what the exact method of randomisation was. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	Allocation concealment is not described. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Blinding of participants and personnel is not described. However, considering the visible difference between the 2 different interventions, blinding was unlikely
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Blinding was unlikely (See above)
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data were available for all participants.
Selective reporting (reporting bias)	Unclear risk	No protocol available. We wrote to study authors
Other bias	Low risk	No other sources of bias were identified

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Xu 2000.

Methods	Study design: Parallel‐group randomised trial Study dates: start date December 1998 ‐ end date May 1999 Setting: Outpatient Country: China
Participants	Inclusion criteria: Not clearly specified. Patient characteristics: main clinical manifestation: suprapubic or perineal discomfort, frequent urination, discomfort during urination, etc. Tenderness during prostate massage, no special body sign otherwise. Routine urine test: WBC < 10/HP. Routine EPS test: WBC > 10/HP. Mid‐stream urine and EPS culture before, during and after the treatment negative. Ultrasound test revealed no bladder or ureter diseases Exclusion criteria: Hyperplasia of the prostate, prostate cancer, tuberculosis of the prostate, etc. Sample size: 60 participants Age (years): Group 1: Antibacterial drugs group (18 ˜ 64, mean: 27.8); Group 2: Prostat group (19 ˜ 63, mean: 28.7) Baseline NIH‐CPSI score: not available All participants were men
Interventions	Group 1 (n = 30): Antibacterial treatment: Trimethoprim plus sulfamethoxazole 2 tablets, by mouth twice a day, 10 days, ofloxacin 0.2 g, by mouth twice a day, 10 days (some of the participants took norfloxacin levofloxacin instead 0.2 g, by mouth twice a day, for 10 days); minocycline 0.1 g, by mouth twice a day, for 10 days (a few of the participants took erythromycin instead 0.5 g, by mouth 4 times a day, for 10 days); sequential therapy of the 3 drugs; repeat every month, duration: 3 months Group 2 (n = 30): Prostat 0.375 g, twice a day, 90 days Co‐interventions: Bland diet; avoid alcohol or tobacco Hip bath with hot water
Outcomes	None of the outcomes relevant to this review
Funding sources	Not mentioned
Declarations of interest	Not mentioned
Notes	Outcomes included: "self‐reported symptomatic relieves, changes in symptomatic scores (SFQ)" with no reference to a validated scale and WBC cell count in prostatic secretions This study was written in Chinese No contact information available
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “60 patients were randomly assigned to 2 groups”. Comment: However, the method for randomisation is not described.
Allocation concealment (selection bias)	Unclear risk	Allocation concealment is not described
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Blinding of participants and personnel is not described. However, considering the visible differences between the 2 interventions, blinding cannot be achieved
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Blinding of outcome assessment is not described. Self‐reported outcomes, participants are not blinded
Incomplete outcome data (attrition bias)   All outcomes	High risk	The paper reported that “in Antibacterial‐drugs Group, the numbers of patients who kept follow‐up at the end of the first, second and third month were 27, 26, and 23, respectively. In Prostat Group, the numbers were 29, 27, and 23 respectively.” 7 participants lost follow‐up in each group, which is 23% attrition
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias were identified

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Yang 2009.

Methods	Study design: Parallel‐group randomised trial Study dates: start date June 2007 ‐ end date December 2007 Setting: outpatient ‐ possibly single centre ‐ national Country: China
Participants	Inclusion criteria: NIH‐CPSI > 10, OR CPSI > 6 plus WBC in EPS > 10/HP; symptoms lasting for at least 6 weeks, such as frequent urination, discomfort urination, perineal pain or discomfort, etc.; routine urine test normal, EPS bacteria culture negative; age 18 to 50 years; patients who did not take any antibiotics, alpha blockers or other herbal medications within 2 weeks; OR patients who took these medications, but agreed to take a 1‐week wash‐out period Exclusion criteria: Patients who have already undertaken intra‐prostate or intra‐vas deferens injection therapy; patients with benign prostate hyperplasia above moderate degree; patients with urethritis, cystitis, pyelonephritis or calculi of the urinary system; patients with organic urination disorders, such as neurogenic bladder; patients with suspected prostate tuberculosis, prostate tumour or eosinophilic granuloma; patients with mental diseases or tumour; patients with chronic or severe diseases of other systems; patients who could not continue treatment or refused examinations; patients who were considered not appropriate for this clinical trial by the researchers Sample size: 160 participants Age (years): Group 1: experimental group: Mean ± SD: 29. 4 ±7.7; Group 2: control group: Mean ± SD: 29.1 ± 7.0) Baseline NIH‐CPSI score: Group 1 = 22.79 (SD 2.56); Group 2 = 22.43 (SD 3.63) All participants were men
Interventions	Group 1 (n = 80): For the first 2 weeks, prednisone acetate tablet 15 mg by mouth once a day For the next 2 weeks, levofloxacin 0.1 g by mouth twice a day for 4 weeks Group 2 (n = 80): For the first 2 weeks, placebo tablet (looks the same as prednisone acetate) by mouth once a day For the next 2 weeks, levofloxacin 0.1 g by mouth twice a day for 4 weeks Co‐interventions: Not specified
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI global and subscore Time points measured: before treatment, Week 2, Week 4 Time points reported: before treatment, Week 2, Week 4 Subgroups: none Adverse Events How measured: Narratively
Funding sources	Not mentioned
Declarations of interest	Not mentioned
Notes	This study was written in Chinese Email: zhaoxiaokun50@163.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “randomized, placebo‐controlled and double‐blinded”, and that “patients were randomly divided into trial group and control group”. Comment: However, we do not know what the method for randomisation is. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	Quote: “randomized, placebo‐controlled and double‐blinded” Comment: Method for allocation concealment is not described. We wrote to study author.
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	Blinding of personnel not described. Participants were blinded. We wrote to study author.
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Quote: “the appearance, packaging design, and taste of the placebo tablet is not significantly different from those of the prednisone acetate tablet”
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: “missing 2 patients of the trial group because of lost follow‐up” Comment: 2.5% attrition in the trial group
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias were identified

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Yang 2010.

Methods	Study design: Parallel‐group randomised trial Study dates: start date June 2009 ‐ end date August 2009 Setting: outpatient ‐ possibly single centre ‐ national Country: China
Participants	Inclusion criteria: NIH‐CPSI > 10, OR NIH‐CPSI > 6 together with WBC/EPS > 10/HP; frequent urination, discomfort during urination, perineal pain/discomfort, or other symptoms lasting for at least 6 weeks; routine urine test normal, EPS bacteria culture negative; age 18 ˜ 50 Exclusion criteria: Men who undertook intra‐prostate, intra‐urethra, or intra‐ureter therapy; men with benign prostate hyperplasia above moderate degree; urethritis, cystitis, pyelonephritis, or stones of the urinary system; patients with neurogenic bladder or other organic urinary dysfunction; patients with suspected prostate tuberculosis, prostate tumour or eosinophilic granuloma; patients who could not persist with the treatment or refused follow‐up; patients who were considered inappropriate for the trial by researchers Sample size: 156 participants Age (years): Group 1: Placebo: Mean ± SD: 30.1 ± 6.2; Group 2: Terazosin: Mean ± SD: 31.0 ± 6.6; Group 3: Tamsulosin ; Mean ± SD: 31.1 ± 6.4 Baseline NIH‐CPSI score: Group 1 = 25.38 (SD 3.73); Group 2 = 25.45 (SD 3.25); Group 3 = 25.49 (SD 3.11) All participants were men
Interventions	Group 1 (n = 52): Placebo tablet (with the same appearance, packaging and taste as tamsulosin tablet) by mouth once a day, 12 weeks Group 2 (n = 52 ): terazosin 1 mg by mouth once a day, 12 weeks Group 3 (n = 52 ): tamsulosin 0.2 mg by mouth once a day, 12 weeks Co‐interventions: 1 week of wash‐out period
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI Time points measured: before treatment, Week 4, Week 8, Week 12 Time points reported: before treatment, Week 4, Week 8, Week 12
Funding sources	Not mentioned
Declarations of interest	Not mentioned
Notes	This study was written in Chinese No contact information available.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “we used random, double‐blinded measures to assign the patients included to 3 groups” (in Chinese) Comment: however it is unclear what the exact method is
Allocation concealment (selection bias)	Unclear risk	The paper reported that they used double‐blinded measures, but the exact method for allocation concealment is not described
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	The paper reported that the placebo tablet shared the same appearance, packaging, taste, and usage as tamsulosin tablet. However it is not clear that participants and personnel were unaware of assignments
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	Blinding of outcome assessment is not described
Incomplete outcome data (attrition bias)   All outcomes	Low risk	2/52 in Group 1 because lost to follow‐up (3.8% attrition) 1/52 each in Groups 2 and 3 because lost to follow‐up (1.9%)
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias detected

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Ye 2006.

Methods	Study design: Parallel‐group randomised trial Study dates: From September 2005 to March 2006 Setting: Outpatient Country: China
Participants	Inclusion criteria: Individuals between 18 and 50 years old who had a NIH‐CPSI > 10, OR NIH‐CPSI > 6 plus WBC in expressed prostatic secretion > 10/HP; symptoms lasting for > 6 weeks. Patients did not take antibiotics, alpha blockers, or other herbal medications within 2 weeks before the trial starts, OR patients who took medications but agreed to undertake a 1‐week wash‐out Exclusion criteria: Patients who have already undertaken intra‐prostate or intra‐vas deferens injection therapy. Patients with benign prostate hyperplasia above moderate degree. Patients with urethritis, cystitis, pyelonephritis or calculi of the urinary system. Patients with organic urination disorders, such as neurogenic bladder. Patients with suspected prostate tuberculosis, prostate tumour or eosinophilic granuloma. Patients with mental diseases or tumour. Patients with chronic or severe diseases of other systems. Patients who could not continue treatment or refused re‐examinations. Patients who were considered not appropriate for this clinical trial by the researchers Sample size: 160 participants Age (years): Group 1: trial group: Mean ± SD: 31.23 ± 8.03; Group 2: control group: Mean ± SD: 31.84 ± 6.39 Baseline NIH‐CPSI score: not available All participants were men
Interventions	Group 1 (n = 80 ): For 8 weeks, Prostat^® 1 tablet(0.375 g) by mouth twice a day (Serenoa repens) Group 2 (n = 80): For 8 weeks, Placebo 1 tablet by mouth twice a day Co‐interventions: Levofloxacin 1 tablet (0.1 g) by mouth twice a day for the first 4 weeks
Outcomes	Prostatitis symptoms How measured: NIH‐CPSI subscore Time points measured: before treatment, Week 4 after treatment, Week 8 after treatment Time points reported: before treatment, Week 4 after treatment, Week 8 after treatment Subgroups: none Adverse events How measured: Narratively
Funding sources	Not mentioned
Declarations of interest	Not mentioned
Notes	This study was written in Chinese Contact information not available
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “multi‐center, double‐blinded, parallel randomized controlled trial”. Comment: We do not know what the method for randomisation is
Allocation concealment (selection bias)	Unclear risk	Quote: “randomized, placebo‐controlled and double‐blinded”, Comment: Method for allocation concealment is not described.
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	Quote: “the appearance, packaging design, and taste of the placebo tablet is not significantly different from those of the Prostat®”
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Blinding of outcome assessment is not described. Self‐reported outcomes, participants are not blinded
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: “one patient from the trial group dropped out”, 1.25% attrition in the trial group, but we do not know the reason
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias were detected

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Ye 2008.

Methods	Study design: Parallel‐group randomised trial Study dates: start date December 2002 ‐ end date August 2004 Setting: outpatient ‐ possibly single centre ‐ national Country: China
Participants	Inclusion criteria: men, aged 18 – 50 years, with a diagnosis of chronic nonbacterial prostatitis were eligible for inclusion, NIH‐CPSI score of > 10 or a total NIH‐CPSI score of > 6 with a WBC count of > 10 cells/high power field and continuous symptoms of prostatitis for 6 weeks Exclusion criteria: participants who had been treated with alpha‐adrenergic antagonists or antibiotics in the period 4 weeks prior to the start of the study Sample size: 105 participants randomised Age (years): Not available. NIH‐CPSI baseline score: Group 1 (n = 42, comprised 2 groups of 21 participants with type IIIA and type IIIB) 15.19 (SD 4.78) and 15.38 (SD 4.12); Group 2 (comprised 2 groups of 21 participants with type IIIA and type IIIB) 24.9 (SD3.16) and 17.38 (SD 3.22); Group 3 = 16.05 (SD 3.99) All participants were men
Interventions	Participants were divided in 5 groups according their subtype of CP/CPPS (type A and type B). For this review, we group them in three categories according to their received treatment Group 1 (n = 42, comprised of two groups of 21 participants with type IIIA and type IIIB): tamsulosin 0.2 mg daily for 90 days Group 2 (n = 42, comprised of two groups of 21 participants with type IIIA and type IIIB): tamsulosin 0.2 mg daily and levofloxacin 0.2 g after breakfast daily for 90 days Group 3 (n = 21, only type IIIA participants): Levofloxacin 0.2 g after breakfast daily for 90 days Co‐interventions: Not available
Outcomes	Prostatitis symptoms How measured: NIH‐CPSI score Time points measured: baseline, 45 and 90 days Time points reported: baseline, 45 and 90 days Adverse events How measured: Narratively
Funding sources	Quote: “This research was supported by funds from Astellas Pharma China Inc”
Declarations of interest	Quote: “The authors had no conflicts of interest to declare in relation to this article.”
Notes	Contact information: ruzhulan@yahoo.cn (email bounced)
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Quote: “Patients and healthcare workers were not blinded to the treatment regimens.”
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Quote: “Patients and healthcare workers were not blinded to the treatment regimens.”
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: Quote: "All patients completed the treatments and were scored according to prostatitis symptoms in follow‐up checks"
Selective reporting (reporting bias)	Unclear risk	No protocol available. We wrote to study authors
Other bias	High risk	Large baseline differences in NIH‐CPSI scores. No other baseline characteristics were reported

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Youn 2008.

Methods	Study design: Parallel‐group randomised trial Study dates: start date October 2005 ‐ end date May 2006 Setting: outpatient ‐ single institute ‐ national Country: South Korea
Participants	Inclusion criteria: men with symptoms of chronic prostatitis, EPS WBC ≥ 10/HPF (IIIa). Participant with NIH‐CPSI has reported total score of 15 or more Exclusion criteria: Men with prior treatment of chronic prostatitis, positive culture on urine or EPS culture, or prostate volume ≥ 30 gm on DRE Sample size: 69 Age (years) Group 1 = 41.3 ± 9.5 (21 ‐ 57); Group 2 = 41.8 ± 9.2 (23 ‐ 60) Baseline NIH‐CPSI score: Group 1 = 24.0 ± 6.3; Group 2 = 24.7 ± 6.9 All participants were men
Interventions	Group 1: gatifloxacin (200 mg, twice a day, Gatiflo^Ⓡ) and doxazosin (Cardura^Ⓡ, dose was not defined) for 6 weeks Group 2: gatifloxacin alone (200 mg, twice a day, Gatiflo^Ⓡ) for 6 weeks Co‐interventions: no information
Outcomes	Prostatitis Symptoms How measured: NIH CPSI questionnaire Time points measured: baseline, 6 weeks Time points reported: baseline, 6 weeks Subgroups: no
Funding sources	Not reported
Declarations of interest	Not reported
Notes	Language of publication: Korean Email: sbryu@chonnam.ac.kr
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	No information available. We wrote to study authors
Blinding of outcome assessment (detection bias)   Subjective outcomes	Unclear risk	No information available. We wrote to study authors
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	No information available. We wrote to study authors
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias detected

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Zeng 2004.

Methods	Study design: Parallel‐group randomised trial Study dates: Start date 15 June 2003 ‐ end date 26 August 2003 Setting: outpatient ‐ possibly single centre ‐ national Country: China
Participants	Inclusion criteria: According to the diagnostic criteria of chronic prostatitis by NIH‐CPCRN (Alexander 2004a) Exclusion criteria: Patients who had suspected or confirmed urethritis or cystitis; Patients with suspected or confirmed prostate hyperplasia or prostate cancer by intra‐rectal ultrasound exam; 3‐cup test or PPMT test confirmed VB3 or bacterial infection; EPS immunologic test for chlamydia or mycoplasma positive; antibiotics treatment effective in the early stages; Patients complicated by other serious diseases which necessitate medication; Patients allergic to sulfanilamide drugs Sample size: 64 participants Age (years): Group 1: 21 ˜ 48, mean 34.4; Group 2: 19 ˜ 53, mean 36.8 Baseline NIH‐CPSI score: Group 1 = 29.6 (SD 1.8); Group 2 = 27.1 (SD 1.5) All participants were men
Interventions	Group 1 (n = 32): For 6 weeks, celecoxib 200 mg by mouth once a day Group 2 (n = 32): For 6 weeks, celecoxib 200 mg by mouth twice a days Co‐interventions: Discontinue any medication for at least 1 week before the trial started. Not to take any other medication for prostatitis during the trial period
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI global and pain subscore Time points measured: 1 day before treatment, Weeks 2, 4, and 6 after taking medication Time points reported: 1 day before treatment, Weeks 2, 4, and 6 after taking medication Subgroups: none Adverse Events How measured: Narratively
Funding sources	Not mentioned
Declarations of interest	Not mentioned
Notes	This study was written in Chinese Email: xyzeng@tjh.tjmu.edu.cn
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “64 patients were randomly assigned to two groups”. Comment: We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Blinding of participants and personnel is not described. However, the difference between the interventions of the 2 groups is visible
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	Blinding of outcome assessment is not described. Self‐reported outcomes, participants are not blinded
Incomplete outcome data (attrition bias)   All outcomes	Low risk	In Group A, 2 participants dropped out (2/30); In Group B, 1 participant dropped out (1/30); Reasons for dropping out are not adequately described
Selective reporting (reporting bias)	Unclear risk	No protocol available. We wrote to study authors
Other bias	Low risk	No other sources of bias were detected

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Zhang 2007.

Methods	Study design: Parallel‐group randomised trial Study dates: start date January 2005 ‐ end date May 2007 Setting: Outpatient ‐ possibly single centre ‐ national Country: China
Participants	Inclusion criteria: Western Medicine criteria: patients who met the CP/CPPS criteria and PPMT criteria. (Krieger JN, Nyberg L Jr, Nickel JC. NIH consensus definition and classification of prostatitis. JAMA 1999] [Nickel JC. The Pre and Post Massage Test(PPMT): a simple screen for prostatitis. Tech Urol 1997) Traditional Chinese Medicine criteria: patients who met the “combination of TCM and Western Medicine criteria for chronic prostatitis” (www.adpycn.com, 2004) Exclusion criteria: Patients who had urinary infection, chronic epididymis, hyperplasia of the prostate, or suspected or confirmed prostate cancer; Patients with diseases of other systems or psychiatric disorders Sample size: 248 participants (30 participants dropped out) Age (years): Group A: 25 ˜ 50 (Mean ± SD: 32.42 ± 7.29); Group B: 23 ˜ 48 (Mean ± SD: 29.44 ± 5.28); Group C: 22 ˜ 50 (Mean ± SD: 31.23 ± 8.83); Group D: 22 ˜ 50 (Mean ± SD: 30.79 ± 7.64) Baseline NIH‐CPSI score: Group A = 22.98 ± 5.95; Group B = 20.98 ± 7.27; Group C = 21.61 ± 6.69; Group D = 20.05 ± 7.43 All participants were men
Interventions	Group A (n = 58): For 4 weeks, Aike decoction twice a day, 1 pack each time Group B (n = 50): For 4 weeks, Bazhengsan decoction twice a day, 1 pack each time Group C (n = 62): For 4 weeks, Prostatitis decoction twice a day, 1 pack each time Group D (n = 48): For 4 weeks, Placebo capsule 3 times a day, 3 capsules each time Co‐interventions: No information
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI global and subscore Time points measured: before treatment, Week 2, Week 4 Time points reported: before treatment, Week 2, Week 4 Subgroups: none Adverse Events How measured: Narratively
Funding sources	Subsidisation Programme of Department of Education of Fujian Province (No. JA02229)
Declarations of interest	Not mentioned
Notes	This study was written in Chinese Email:zmj83@tom.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “218 patients were randomly assigned to 4 groups according to random sequence chart” Comment: However, the exact method for using the random sequence chart is not clear. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	The article reported that there was allocation concealment, but the exact method for concealment is unknown. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	Quote: “the decoctions was uniformly packaged, shared the same appearance, and had a number printed on the package. The doctors gave out the drug to the patients according to the number of the drugs, and did not know what is contained in the package”. Comment: However, different decoctions could vary in taste; additionally, the placebo tablet used in Group D was visibly different from decoction, and therefore blinding was not possible
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	The article reported that there was blinding of outcome assessment. Self‐reported outcomes, however, participants are not blinded
Incomplete outcome data (attrition bias)   All outcomes	High risk	Quote: “30 patients dropped out in the middle of the trial and were not included in the statistics”(30/248), 12% attrition
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias were identified

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Zhang 2017.

Methods	Study design: Parallel‐group randomised trial Study dates: start date January 2011 ‐ end date January 2012 Setting: outpatient ‐ possibly single centre ‐ national Country: China
Participants	Inclusion criteria: > 18 years and diagnosed with CP/CPPS with discomfort or pain symptoms in the pelvic area for at least 3 months NIH‐CPSI score ≥ 15 points; pain score should be ≥ 4 points Exclusion criteria: previous treatment with doxazosin or other alpha‐adrenergic receptor blockers for CP/CPPS or for any other reason in the past; urinary tract infection; genital herpes in the past 3 months; 5‐alpha‐reductase inhibitor for 3 months in the past year; unilateral testicular pain without pelvic area symptoms; urinary or reproductive system cancer; inflammatory bowel disease; active urethral stricture; prostate or bladder operation history; neurogenic bladder; or the usage of a strong P‐3A4 enzyme inhibitor (ketoconazole, itraconazole, ritonavir, etc.) or erythromycin; additionally, patients with mania, bipolar disorder, psychosis, or who were identified as a suicide risk by researchers were excluded; plus, those patients who used monoamine oxidase inhibitors or who had liver disease or other serious diseases in the 2 weeks before screening were also excluded Sample size: 150 participants randomised Age (years): Group 1 = 32.51 (22.58); Group 2 = 33.59 (range 20 ‐ 67); Group = 32.78 (range 23 ‐ 62) NIH‐CPSI baseline score: Group 1 = 21.78; Group 2 = 22.18; Group 3 = 21.85 All participants were men
Interventions	Group 1 (n = 50): sertraline 50 mg daily, adjusted to 25 or 100 mg according to efficacy and tolerability + doxazosin; 6 months Group 2 (n = 50): duloxetine 30 mg daily, titrated to 60 mg and then 120 mg daily if tolerated (otherwise 60 mg daily + doxazosin); 6 months Group 3 (n = 50): doxazosin 4 mg daily; 6 months Co‐interventions: not available
Outcomes	Prostatitis symptoms How measured: NIH‐CPSI score Time points measured: baseline, 1, 3 and 6 months Time points reported: baseline, 1, 3 and 6 months Anxiety and Depression How measured: Hospital Anxiety and Depression scale (HAD) Time points measured: baseline, 1, 3 and 6 months Time points reported: baseline, 1, 3 and 6 months Adverse events How measured: Narrative
Funding sources	None
Declarations of interest	None
Notes	Phase I: run‐in period Phase II: 6‐month treatment period Phase III: withdrawal of treatment for 2 weeks Email: zmxyansu@126.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	The interventions were visibly different, and personnel actively manipulated the interventions differently. Blinding was unlikely
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	The interventions were visibly different, and personnel actively manipulated the interventions differently. Blinding was unlikely
Incomplete outcome data (attrition bias)   All outcomes	High risk	All outcomes: outcome data were not available for 9/50 participants in the doxazosin group, 9/50 in the sertraline group and 6/50 in the duloxetine group
Selective reporting (reporting bias)	Unclear risk	No protocol available
Other bias	Low risk	No other sources of bias were identified

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Zhao 2009.

Methods	Study design: Parallel‐group randomised trial Study dates: start date August 2006 ‐ end date January 2008 Setting: outpatient ‐ possibly single centre ‐ national Country: China
Participants	Inclusion criteria: Participants with CP/CPPS diagnosis refractory (patient unsatisfied with their clinical response) to standard conventional therapy (antibiotics, α‐blockers); aged 18 to 58 years, symptoms > 6 months with ≥ 1 month of treatment with appropriate antibiotics or/and alpha blockers; negative infection screening, including the 4‐glass test and bacterial localisation studies; total NIH‐CPSI score of 14 or more; NIH‐CPSI pain score of 8 or more at baseline Exclusion criteria: “presence of chronic bacterial prostatitis after a 4‐glass lower urinary tract localization test; previous urinary tract infection or a uropathogen documented within the last year; cancer of the genitourinary tract; a history of active genital herpes within the previous year; active urethral stricture; inflammatory bowel disease; a history of pelvic radiation or systemic chemotherapy; a history of intravesical chemotherapy; prostate or bladder surgery, and neurologic disease affecting the bladder” Sample size: 64 participants were randomised Age (years): not available NIH‐CPSI baseline score: not available All participants were men
Interventions	This study included a 2‐week placebo run‐in. Group 1 (n = 32): Celecoxib 200 mg daily for 8 weeks Group 2 (n = 32): Matching placebo for 8 weeks Co‐interventions: not available
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score and responder analysis Time points measured: baseline and weekly for 8 weeks Time points reported: baseline and weekly for 6 (numerically) and 8 weeks (graphically) Adverse Events How measured: Narratively
Funding sources	Not available
Declarations of interest	Not available
Notes	Contact information: zwpzju@yahoo.cn (email bounced)
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated (Excel spreadsheet)
Allocation concealment (selection bias)	Unclear risk	No information available. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	Double‐blind study. Participants were blinded, no information about blinding of study personnel. We wrote to study authors
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Participants were blinded using placebo
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: outcome data were available for all participants
Selective reporting (reporting bias)	High risk	NIH‐CPSI scores were presented graphically. We wrote to study authors
Other bias	Unclear risk	Baseline characteristics not available. We wrote to study authors

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Zhao 2019.

Methods	Study design: parallel group randomized trial Study dates: not available Setting: outpatient, national, multicentre Country: China
Participants	Inclusion criteria: participants with type IIIB prostatitis (following the 2014 Chinese Urological Association CUA guidelines: long‐term or repeated pelvic pain or discomfort with varying degrees of micturition symptoms and sexual dysfunction for a duration ≥3 months, normal prostatic fluid and negative VB3 testing) and premature ejaculation (lifelong premature ejaculation or a clinically significant reduction in latency time, often up to approximately 3 min or less (acquired premature ejaculation) and accompanied by associated distress such as annoyance, depression and/or avoidance of intimacy), aged between 18 and 45 years old, with a fixed sexual partner and a regular sex life for at least 6 months (and three or more sexual encounters in the past month) and had 1–2 sexual encounters per week during the treatment process. Exclusion criteria: participants with comorbid mental disorders, cardio‐cerebrovascular diseases, liver and kidney insufficiency, alcohol dependence, hepatitis B/HCV/HIV infection, etc.; erectile dysfunction; those who had received serotoninergic drugs, SSRIs, TCAs, PDE5i or P450 3A4 inhibitor in the last 4 weeks or received these drugs during the study period; and intolerance to dapoxetine or tamsulosin. Sample size: 251 participants randomized Age (years): Group 1 mean 33.9 (SD 6.56) years Group 2 mean 31.2 (SD 5.96) years NIH‐CPSI baseline score: Group 1 mean 24.29 (SD 5.92) Group 2 mean 26.15 (SD 7.76) Sex (M/F): All participants were men
Interventions	Group 1 (n = 168): 30 mg dapoxetine before sexual activity and 0.2 mg tamsulosin once a day for 12 weeks. Group 2 (n = 83): only co‐interventions for the same period. Co‐interventions:tamsulosin hydrochloride sustained‐release capsule (0.2 mg, once a day)
Outcomes	Prostatitis symptoms How measured: NIH‐CPSI score Time points measured: baseline, 4 and 8 weeks Time points reported: baseline, 4 and 8 weeks Subgroups: none Sexual dysfunction How measured: Premature Ejaculation Profile (PEP) Time points measured: baseline, 4, 8 and 12 weeks Time points reported: baseline, 4, 8 and 12 weeks Subgroups: none Adverse events How measured: Narratively
Funding sources	National Key R&D Plan of China (2017YF1002003); National Natural Science Foundation of China (81671512, 81701524 and 8170060493).
Declarations of interest	Not available
Notes	Baseline characteristics were available for participants who completed the 12‐week follow‐up (see risk of bias judgements for details regarding attrition). Most outcome data were available graphically at 4 and 8 weeeks. Contact information: Shujie Xia and Zheng Li Emails: xsjurologist@163.com (SX); lizhengboshi@sjtu.edu.cn (ZL) Clinical Trial Registry: ChiCTR1800019441
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Patients were randomly divided into two treatment groups in a ratio of 1:2." Insufficient information to make a judgement.
Allocation concealment (selection bias)	Unclear risk	Quote: "Patients were randomly divided into two treatment groups in a ratio of 1:2." Insufficient information to make a judgement.
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	The interventions were visibly different. Blinding was unlikely.
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	The interventions were visibly different. Blinding was unlikely.
Incomplete outcome data (attrition bias)   All outcomes	High risk	Quote: "Follow‐up data were available for 228, 182 and 114 participants at 4 weeks, 8 weeks and 12 weeks of treatment respectively". Attrition of outcome data (all outcomes) was 10%, 27% and 55% respectively. Reasons for withdrawal were not specified.
Selective reporting (reporting bias)	Unclear risk	The clinical trial registry offered insufficient information regarding timepoints and outcomes measured and reported in the trial.
Other bias	Low risk	No other sources of bias were identified.

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Zhou 2008.

Methods	Study design: Parallel‐group randomised trial Study dates: start date October 2005 ‐ end date March 2007 Setting: outpatient ‐ possibly single centre ‐ national Country: China
Participants	Inclusion criteria: Participants diagnosed with CPPS who had undergone conventional clinical treatment, including antibiotics, anti‐inflammatory agents, alpha blockers, phytotherapy, prostatic massage and transrectal ultrasonography of prostate and for whom the treatments had failed and who had no allergy to tetracycline Exclusion criteria: not available. Sample size: 48 participants randomised Age (years): range 29 to 50 NIH‐CPSI baseline score: available graphically All participants were men
Interventions	Group 1 (n = 24): 500 mg tetracycline HCL orally plus 0.4 g vitamin C and 0.2 g co‐vitamin B daily for 3 months. Group 2 (n = 24): only vitamin B (as “placebo”) for the same period Co‐interventions: not available
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline and 3 months Time points reported: baseline and 3 months (graphically)
Funding sources	Not available
Declarations of interest	Not available
Notes	This study focused on the detection of nano‐bacteria (this outcome was not included in our review) Contact information: song‐bo‐2007@hotmail.com (email bounced)
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. We wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. We wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	High risk	The study refers to the use of placebo in the control group, but the interventions were visibly different. Blinding was unlikely
Blinding of outcome assessment (detection bias)   Subjective outcomes	High risk	The study refers to the use of placebo in the control group, but the interventions were visibly different. Blinding was unlikely
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcome: outcome data were available for all participants
Selective reporting (reporting bias)	High risk	Data were presented graphically. NIH‐CPSI scores were available only in 1 group. We wrote to study authors
Other bias	Unclear risk	Baseline characteristics were missing. We wrote to study authors

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Ziaee 2006.

Methods	Study design: Parallel‐group randomised trial Study dates: start date September 2002 ‐ end date September 2004 Setting: outpatient ‐ possibly single centre ‐ national Country: Iran
Participants	Inclusion criteria: Participants with pain in penis, perineal region, supra‐pubic, testis and/or pelvis after ejaculation alongside voiding symptoms such as dysuria, frequency and sense of incomplete urination; symptoms duration > 1 year and NIH‐CPSI score > 14; aged 20 to 40 years; normal abdominal palpation; negative 4‐glass study Exclusion criteria: Men with a medical history of documented urinary tract infection, sexually transmitted disease, urethral stricture, neurological disease, drugs which mimic these symptoms (for example, anticholinergics and psychotropics), haematuria and pyuria; abnormal ultrasonography or other imaging; urinary system disease and genitourinary system surgery Sample size: 56 participants randomised Age (years): Group 1 mean = 33.28 (SD 6.4); Group 2 mean = 33.52 (SD 6.15) NIH‐CPSI baseline score: Group 1 mean = 26.28 (SD 5.5); Group 2 mean = 25.07 (SD 6.53) All participants were men
Interventions	Group 1 (n = 29): allopurinol 100 mg 3 times a day for 3 months in addition to ofloxacin for the first 3 weeks Group 2 (n = 27): matching placebo and ofloxacin in the same posology Co‐interventions: not available
Outcomes	Prostatitis Symptoms How measured: NIH‐CPSI score Time points measured: baseline, 1, 2 and 3 months Time points reported: baseline, 1, 2 and 3 months Adverse Events How measured: Narratively
Funding sources	Not available
Declarations of interest	None
Notes	Dr. Amir Mohsen Ziaee: ziaee@hotmail.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information available. Wrote to study authors
Allocation concealment (selection bias)	Unclear risk	No information available. Wrote to study authors
Blinding of participants and personnel (performance bias)   Subjective outcomes	Unclear risk	Double‐blind study. No information regarding the blinding of personnel. Participants were blinded. Wrote to study authors
Blinding of outcome assessment (detection bias)   Subjective outcomes	Low risk	Participants were blinded using placebo
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All outcomes: Quote: “All patients were followed to the end of the study (no loss to follow‐up)."
Selective reporting (reporting bias)	Unclear risk	No protocol available. Wrote to study authors
Other bias	Low risk	No other sources of bias identified

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AUA: American Urological Association; BCG: bacillus Calmette‐Guerin; BPH: benign prostatic hyperplasia; DRE: digital rectal examination; EPS: expressed prostatic secretions IPSS: International Prostatic Symptom score;s LUTS: lower urinary tract symptom; TURP: transurethral resection of the prostate

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Abdel‐Meguid 2018	Controlled clinical trial. Participants were assigned to control by preference.
Aliaev 2006	Non‐randomised comparative study for Sabal serrulata plant extract (study in Russian)
Allen 2017	Non‐randomised controlled trial of thermobalancing therapy for CP/CPPS
Barbalias 1998	Includes participants with bacterial prostatitis. CP/CPPS definition does not include pain
Bschleipfer 2007	"Intraprostatic botulinum toxin A injection" trial. Personal contact with the author confirmed that the trial was stopped due to problems in recruiting (prospective participants with high levels of liver enzymes)
Chen 2016	The study included participants with type II, IIIA, and IIIB chronic prostatitis in their trials and did not present disaggregated results.
Colleen 1975	Non‐randomised cross‐over comparative study for minocycline
DRKS00009352	Non‐randomised controlled trial for a physiotherapeutic device and thermobalancing therapy
El‐enen 2015	Non‐controlled study for botulinum toxin A
Evliyaoğlu 2002	Quasi‐randomised study of doxazosin vs placebo
Feng 2011	This trial of nursing interventions included participants with bacterial prostatitis
Galeone 2012	Prolexan trial. 60% had bacterial prostatitis, no disaggregated results were available
Glybochko 2014	Electrode plasmapheresis for chronic bacterial prostatitis
Golubchikov 2005	Non‐randomised controlled trial for a "combined treatment including complex physical factors"
Hong 2008	Abdominal cluster needle, quasi‐randomised trial (randomisation is based on date of admission)
Ikeuchi 1990	This study was assessed by Cochrane Japan collaborators. It was found to be a non‐randomised study for kampo medicine
ISRCTN43221600	Non‐randomised study for a "combined psycho‐ and physiotherapeutic treatment program for patients with chronic pelvic pain syndrome (CPPS)"
Kalinina 2015	Non‐randomised trial for a dietary supplement Prostatinol
Kamalov 2006	Non‐randomised trial for rectal suppositoria Vitaprost
Kogan 2010	Non‐randomised controlled trial for "magnetolaser therapy"
Kotarinos 2009	Observational study secondary to a myofascial trigger point release RCT (included in the twin review Non‐Pharmacological Interventions for treating chronic prostatitis/chronic pelvic pain syndrome)
Lee 2006b	Non‐randomised study for "Uro‐Vaxom"
Leng 2007	Non‐randomised study for a combination of traditional Chinese medicine and Western medicine
Lokshin 2010	Trial for "combination (ciprofloxacin+doxazosin) vs monotherapy (ciprofloxacin)". This trial included participants with bacterial prostatitis
Lopatkin 2009	Non‐randomised controlled study for vitaprost (translated from Russian)
Loran 2003	Non‐randomised controlled study for Gentos
Ma 2015	Quasi‐randomised study for "catgut embedding therapy"
Marx 2013	Report of a single arm of the osteopathy trial after 5 years (included in the twin review Non‐Pharmacological Interventions for treating chronic prostatitis/chronic pelvic pain syndrome)
Minjie 2017	The definition of the study population was not according to NIH criteria
NCT00194597	Trial for viagra (Sildenafil). This study has been terminated due to illness of PI
NCT00194623	This study on botox has been terminated since re‐organisation of personnel forced termination
NCT00194636	This study on "Sympathetic Plexus Block" has suspended participant recruitment. (PI health issues)
NCT00301405	This study on thalidomide has been terminated. (Study closed. Difficult enrollment of patients with prostatitis)
NCT00464373	Trial of Botulinum Toxin Type A as a single intrasphincteric injection. This study was terminated due to slow accrual
NCT00529386	Personal contact with the author (Dr. Nickel): trial stopped for futility before endpoint, it was never published, "8 patients received botox as per protocol 1 patient had mild improvement". Based on slow enrollment, poor results, the trial was discontinued. No follow‐up or report other than to the Institutional Review Board
NCT01678911	This study on Gralise(R) has been terminated due to difficulties in recruitment and low enrollment
NCT01830829	This study was terminated due to difficulty in enrolling participants. Study for JALYN (dutasteride‐tamsulosin combination)
NCT02042651	This study has been withdrawn prior to enrolment
NCT03500159	Study on the effects of AQX‐1125. This study was terminated due to the decision of the Sponsor
Nickel 2011b	Analysis of the effects of dutasteride in participants with CP/CPPS symptoms. The included participants were not evaluated to reach a diagnosis of CP/CPPS. The randomised controlled trial's objective is the prevention of prostate cancer
Nishino 2017	Single‐arm trial of tadalafil for CP/CPPS
Osborn 1981	Non‐randomised study cross‐over trial of muscle relaxants
Pavone 2010	Non‐randomised study of Serenoa repens for people with lower urinary tract symptoms (LUTS)
Pushkar' 2006	The active treatment and the comparison groups comprised 27% (6 out of 22) of bacterial prostatitis patients. There were no disaggregated data for CP/CPPS participants
Razumov 2005	Non‐randomised study of "combined physiotherapy"
Simmons 1985	The definition of CP/CPPS does not match the current definition. In fact some participants had "non‐specific urethritis" and 6 participants were asymptomatic at the beginning of the study
Stamatiou 2014	Quasi‐randomised study of antibiotic vs phytotherapeutic therapy
Takahashi 2005	This study was assessed by Cochrane Japan collaborators. It was found to be a non‐randomised study for levofloxacin and cernitin pollen extract
Thin 1983	Non‐randomised study for the comparison of "minocycline, trimethoprim, co‐trimoxazole or diazepam"
Tkachuk 2006	Non‐randomised study for "Vitaprost"
Tkachuk 2011	Non‐randomised study for "Vitaprost" as add‐on therapy to physiotherapy
Wagenlehner 2017	This study was a Phase II, dose‐finding study with an adaptive randomisation design.
Xu 2004	Non‐randomised study of combination therapy (antibiotics, alpha blockers, traditional Chinese medicine, etc.)
Zhang 2011	he diagnosis of CP/CPPS was not according to the review definition. The authors referred to the presence of both "Chinese medicine (CM) Gan (肝)‐qi stagnancy syndrome type" and benign prostatic hyperplasia (BPH)

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Characteristics of studies awaiting assessment [ordered by study ID]

EUCTR2005‐001849‐42‐IT.

Methods	A randomised, double‐blind, placebo‐controlled, parallel‐group study to determine the effect of BXL628 in patients with Chronic Non‐Bacterial Prostatitis category III Chronic Pelvic Pain Syndrome, CP/CPPS Method: Randomised controlled trial, double‐blind, phase II study Trial status: completed
Participants	Adults with CP/CPPS (no further information provided), estimated n = 120
Interventions	Intervention: BXL628 150 µg Control: Placebo
Outcomes	Not available.
Notes	Sponsor: BIOXELL SPA Contact: pharmacovigilance@bioxellpharma.com, Admin@bioxellpharma.com, MarketingManager@bioxellpharma.com, CEO@bioxellpharma.com, Info@bioxellpharma.com (no response) Data extracted from: www.clinicaltrialsregister.eu/ctr‐search/trial/2005‐001849‐42/IT

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ISRCTN46815629.

Methods	A randomised placebo‐controlled study of tamsulosin, voltarol and the combination in types IIIa and IIIb prostatitis using the newly developed and validated National Institutes of Health (NIH) symptom score Method: Randomised controlled trial Overall trial start date: 04 May 2000 Overall trial end date: 03 November 2003
Participants	Participant inclusion criteria: 60 men aged between 30 and 50 Participant type: no further specifications Target number of participants: 60 Participant exclusion criteria: not provided at time of registration
Interventions	1. Placebo only 2. Tamsulosin 3. Voltarol 4. Tamsulosin and Voltarol
Outcomes	Quote: "The main outcome measure will be a reduction in the National Institute of Health Chronic Prostatitis Symptom Index (NIHCPSI), which is a newly produced and validated symptom score for assessing men with this condition."
Notes	Funder name: Cambridge Consortium ‐ Addenbrooke's (UK) Contact: contactcentre@addenbrookes.nhs.uk (no response) Data extracted from: www.isrctn.com/ISRCTN46815629

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Kulchavenya 2018.

Methods	This study had two stages: The first stage is a descriptive study in patients with chronic prostatitis. The second stage was an open prospective randomized trial. of patients with CP/CPPS study was conducted. Two groups of patients with chronic nonbacterial prostatitis with signs of inflammation were formed. A control group (n=29) received standard treatment, rectal 0.5 methyluracil suppositories three times per week, 20 suppositories per course. In addition to the standard treatment, the patients of the study group (n=31) were administered Longidaza 3000 IU rectal suppositories also three times a week, 20 suppositories per course.
Participants	Participants with CP/CPPS
Interventions	Control group (n=29): "standard treatment" with rectal 0.5 methyluracil suppositories three times per week, 20 suppositories per course. Intervention group (n=31): longidaza 3000 IU rectal suppositories also three times a week, 20 suppositories per course.
Outcomes	Fibrous connective tissue formation Prostatitis symptoms
Notes	The report of this study included only the histopathological outcomes. We wrote to study authors: urotub@yandex.ru (no response)

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NCT00236990.

Methods	An effectiveness and safety study of ELMIRON (pentosan polysulfate sodium) for the treatment of chronic non‐bacterial inflammation of the prostate gland Study type: Interventional, randomised, parallel assignment, clinical trial  Masking: Double Enrolment: 283  Study completion date: September 2005
Participants	Inclusion criteria: diagnosis of chronic non‐bacterial prostatitis/chronic pelvic pain syndrome symptoms of discomfort or pain in the perineal and/or pelvic region (lower abdomen) for at least 3 of the last 6 months for which there is no recognised cause symptoms persist despite treatment with antibiotics for non‐bacterial prostatitis in the past 6 months. Exclusion criteria: clinically significant medical problems or other organ abnormalities psychiatric disorders urinary tract infection during the last 3 months history of bladder, urethral or prostate cancer Prostate Specific Antigen (PSA) ≥ 4 ng/mL diagnosis or treatment for genital herpes or herpes flare within the last year
Interventions	Quote: "The objective of this randomized, double‐blind, placebo‐controlled study is to determine the effectiveness and safety of ELMIRON® 100 mg three times per day for 12 weeks, as compared with placebo"
Outcomes	Primary outcome measures: Change in total NIH‐CPSI score from baseline to Week 12  Secondary outcome measures: Participant‐reported Global Response Assessment at Week 12. Brief Male Sexual Function Index at Weeks 4, 8, and 12. Pelvic Pain Urgency and Frequency symptom scale at Weeks 4, 8, and 12
Notes	Sponsor: McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil‐PPC, Inc We contacted Dr. Nickel since the characteristics of the study were very similar to those of the trial Nickel 2005. However the number of participants randomised and the dose of pentosan are different. Dr. Nickel replied that this could be the trial registry for that study. Data extracted from ClinicalTrials.gov: NCT00236990

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NCT00913315.

Methods	Efficacy Study of Tamsulosin and Tolterodine Treatment for Chronic Prostatitis (ESTTFCP) Study Type: Interventional, randomised, parallel assignment, clinical trial  Masking: Double (Participant, Investigator)  Estimated Enrollment: 30  Study Start Date: August 2009  Estimated Study Completion Date:January 2010  Estimated Primary Completion Date:October 2009 (Final data collection date for primary outcome measure)
Participants	Inclusion criteria: diagnosis of CP/CPPS based on the classification of US National Institutes of Health, aged 18 ‐ 45 years total score of at least 12 on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH‐CPSI) urinary score of at least 4 on the CPSI participants who anticipate improving symptoms Exclusion criteria: previous treatment with any other alpha‐adrenergic receptor blocker and antimuscarinic agents for symptoms of CP/CPPS or for any other reason those who had previous urinary tract infection within the last year those who had been treated or were taking medication that could affect lower urinary tract function those who met the criteria for chronic bacterial prostatitis after lower urinary tract localisation studies those who had other significant medical problems
Interventions	Experimental: tolterodine 4 mg + tamsulosin 0.4 mg Active comparator: tamsulosin 0.4 mg + placebo
Outcomes	Primary outcome measures: National Institutes of Health Chronic Prostatitis Symptom Index: time frame: 4 months  Secondary outcome measures: Peak urinary flow rate: time frame: 4 months   International Index of Erectile Function: time frame: 4 months
Notes	Xiaohou Wu, MD 86‐2389011122 93404840@qq.com (no response) Sponsors and Collaborators: Chongqing Medical University, Fuling Central Hospital of Chongqing City Data extracted from ClinicalTrials.gov: NCT00913315 This trial was also registered in ChiCTR‐TRC‐09000391 http://www.chictr.org.cn/showprojen.aspx?proj=9142 This registry indicated that sample size would be 160 (80 participants in each arm)

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NCT02385266.

Methods	Treating urological chronic pelvic pain syndrome (UCPPS) pain (UCPPS) Study type: Interventional, randomised, parallel‐assignment, clinical trial  Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)  Official Title: Brain Imaging‐based Strategies for Treating Urological Chronic Pelvic Pain Syndrome (UCPPS) Pain  Enrolment: 20  Study start date: September 2013  Study completion date: June 2016  Primary completion date: May 2016 (Final data collection date for primary outcome measure)
Participants	Inclusion criteria: Men over 18 years of age, with no racial/ethnic restrictions Meets diagnostic criteria for Interstitial Cystitis with Painful Bladder Syndrome (IC/PBS) and/or Chronic Prostatitis with Chronic Pelvic Pain Syndrome (CP/CPPS) Reports symptoms of discomfort or pain in the pelvic or abdominal region for at least a 3‐month period within the last 6 months; Must have a Visual Analog Scale (VAS) pain score > 40 mm (of 100 mm maximum) at the baseline visit (UCPPS pain moderate to severe); Must be in generally stable health Must be willing to abstain from drinking alcohol during the course of the study Must be able to read and speak English and be willing to read and understand instructions as well as questionnaires Must sign an informed consent document after a complete explanation of the study documenting that they understand the purpose of the study, procedures to be undertaken, possible benefits, potential risks, and are willing to participate Exclusion criteria: Urological pain associated with any systemic signs or symptoms, e.g., fever, chills Evidence of a facultative Gram negative or enterococcus with a value of ≥ 100,000 CFU/ml in mid‐stream urine (VB2); Has a second chronic pain condition (e.g. chronic low back pain, temporomandibular joint syndrome, etc.) that would prevent a clear interpretation of the study results History of tuberculous cystitis, bladder cancer, carcinoma in situ, prostate cancer, or urethral cancer History of significant pelvic comorbidities, including inflammatory bowel disease (such as Crohn's disease or ulcerative colitis), has undergone pelvic radiation, systemic chemotherapy, or intravesical chemotherapy, or has been treated with intravesical Bacillus Calmette‐Guerin (BCG) or unilateral orchialgia without other pelvic symptoms, has an active urethral stricture, ureteral calculi, urethral diverticulum, or has a neurological disease or disorder affecting the bladder Significant other medical conditions/diseases, such as significant renal disease or a history of renal insufficiency, unstable diabetes mellitus, congestive heart failure, coronary or peripheral vascular disease, chronic obstructive lung disease, or malignancy Neurologic disorder, including history of seizures Major psychiatric disorder during the past 6 months Moderate or severe depression, as determined by the Hospital Anxiety and Depression Scale, or any active suicidal ideation History of, or current, substance abuse/dependence including alcohol Known sensitivity to D‐cycloserine Currently taking any of the following medications: ethionamide, dilantin, isoniazid (INH), pyridoxine (vitamin B6) Use of therapeutic doses of antidepressant medications (i.e. tricyclic depressants, selective serotonin reuptake inhibitor (SSRIs), serotonin‐norepinephrine reuptake inhibitor (SNRIs); low doses used for sleep may be allowed), as these medications can alter pain transmission;Current use of low dose aspirin; Indication that the participant is unlikely to be compliant due to unmanaged medical or psychological condition(s), including neurological, psychological, or speech/language problems that will interfere with or prevent his understanding of consent, his ability to comply with the protocol or ability to complete the study Any change in medication for urological pain in the last 30 days High‐dose opioid prophylaxis, as defined as > 50 mg morphine equivalent/day Any medical condition that in the investigator's judgment may prevent the individual from completing the study or put the individual at undue risk In the judgement of the investigator, unable or unwilling to follow protocol and instructions Evidence of poor treatment compliance, in the judgement of the investigator Intra‐axial implants (e.g. spinal cord stimulators or pumps) All exclusion criteria for Magnetic Resonance (MR) safety: any metallic implants, brain or skull abnormalities, tattoos on large body parts, and claustrophobia
Interventions	Experimental: D‐Cycloserine 200 mg twice daily and acetominophen when necessary Placebo capsules (lactose)/twice a day and acetaminophen when necessary
Outcomes	Primary outcome measures: Visual Analog Scale (VAS): time frame: 18 weeks after baseline visit Secondary outcome measures: McGill Pain Questionnaire: time frame: 18 weeks after baseline visit Functional Magnetic Resonance Imaging (fMRI) connectivity: time frame: 12 weeks after baseline visit
Notes	Contact: a‐apkarian@northwestern.edu (no response) Sponsor information not available Data extracted from ClinicalTrials.gov: NCT02385266

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Characteristics of ongoing studies [ordered by study ID]

ChiCTR‐IPR‐16010196.

Trial name or title	Effect of saw palmetto extract in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS): a multicenter, randomized, double‐blind, placebo‐controlled trial
Methods	Study design: randomised parallel controlled trial Study dates: 01 January 2017 to 30 June 2018 Setting: outpatient, national/multicentre Country: China
Participants	Inclusion criteria: 1. Male 18 ‐ 50 years old; 2. The participants has pelvic area pain or discomfort at least 3 months prior to admission; 3. The NIH‐CPSI total scores > 10,and pain scores ≥ 4; 4. Men with clinically and laboratory‐diagnosed CP/CPPS; 5. The participants have sexual desire to live at least in the last 3 months; 6. Signed informed consent; 7. Participants could understand the requirements of this trial Exclusion criteria: 1. Urinary tract infection or urine culture positive, clinical diagnosis of urethritis (including urethral mouth secretions, the culture was positive), acute epididymitis patients, patients with suspected prostate cancer; 2. Patients with genital herpes diagnosed or treated within 12 months before admission; 3. Patients with diseases that could affect micturition, such as neurogenic bladder dysfunction or urethral stricture; 4. Patients who have a history of operation or trauma, which affect the evaluation of efficacy of the drug; 5. Patients with severe cardiovascular disease, sexually‐transmitted diseases (including gonorrhoea, chlamydia, mycoplasma or Trichomonas, but does not include any HIV/AIDS), malignant tumour, peptic ulcer, haemorrhage disease; 6. Patients are taking antibiotics, non‐steroidal anti‐inflammatory drugs, alpha receptor blockers, bioflavonoids, Chinese patent medicines and plant drugs for prostatitis; 7. Patients are taking drugs that affect function of bladder outlet and sexual; 8. Patients with insufficiency of liver or kidney, AST or ALT more than 1.5 times the upper limit of normal, creatinine more than the upper limit of normal and with clinical significance; 9. Have a history of allergic reactions of alcohol, study drug or similar drugs; 10. Patients with mental diseases, acrasia, alcohol dependence and drug abuse; 11. In 3 months participated in any other clinical trials, or have birth preparation; 12. Researchers recognised anyone who is not suitable to participate in this clinical study of patients Sample size: 240 participants
Interventions	Intervention (n = 160): Saw palmetto extract 160 mg orally twice daily (duration not available) Control (n = 80): Placebo orally twice daily (duration not available)
Outcomes	Prostatitis symptoms: NIH‐CPSI score (time points not available) Sexual dysfunction: IIEF score (time points not available) Co‐interventions: not described
Starting date	Not available (approved by the ethics committee 15 November 2016)
Contact information	kaizhangpku@163.com; szk_zhanglei@163.com
Notes	Funding: Peking University First Hospital Data extracted from clinical trial registry: ChiCTR‐IPR‐16010196

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IRCT2016022225507N2.

Trial name or title	Effectiveness of pregabalin as an adjuvant therapy for chronic nonbacterial prostatitis
Methods	Study design: Randomised controlled trial, double‐blind, phase II study Study dates: 20 March 2016 ‐ 21 March 2017 (recruitment) Setting: outpatient, probably national and single centre Country: Iran
Participants	Inclusion criteria: 1) Age over 18 years; 2) no prior history of other urinary system disorders such as urinary tract stones, neurogenic bladder, and urinary infections; 3) no history of major underlying diseases such as cirrhosis, renal failure, diabetes, or hypertension; 4) normal levels of urine, fasting blood sugar (FBS), and creatinine; 5) normal results on the first neurological examination of the perineal area, lower limbs, lower limb reflexes, and bulbocavernosus reflex; 6) no use of other medicines; 7) no signs of psychological disorders; 8) confirmed diagnosis of chronic prostatitis; 9) non‐sensitivity to anti‐epileptic drugs, pregabalin, thiazolidinediones, or other anti‐diabetic agents. Exclusion criteria: 1) Unwillingness to continue the study, and 2) major side‐effects due to the use of medications. Target sample size: 288
Interventions	Intervention group: Patients with chronic nonbacterial prostatitis use of terazosin tablets (2 mg) and pregabalin capsules (50 mg) on a daily basis for the first week, followed by the daily use of 100 mg pregabalin capsules for six weeks., measurement of pain, and urinary symptoms after therapy. Control group: Patients with chronic nonbacterial prostatitis use of Terazosin tablets (2 mg) and placebo capsules (50 mg) on a daily basis for the first week, followed by the daily use of 100 mg placebo capsules for six weeks, measurement of pain, and urinary symptoms after therapy.
Outcomes	Evaluation and comparison of pain, urinary symptoms, quality of life, and side‐effects of medications between the intervention and control groups, based on the scoring system introduced by the NIH‐CPSI score (at 6 weeks).
Starting date	20 March 2016
Contact information	Contact information: m‐jiriaie@mscstu.scu.ac.ir (Ali Serous)
Notes	Funding source: Vice Chancellor for Research of Arak University of Medical Sciences Data extracted from clinical trial registry: IRCT2016022225507N2

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IRCT2016071025507N4.

Trial name or title	A clinical trial to comparison the effectiveness of melatonin and capsules containing starch (placebo) as an adjuvant therapy to control symptoms of chronic nonbacterial prostatitis patients
Methods	Study design: Randomised controlled trial, double‐blind, phase II study Study dates: 22 August 2016 ‐ 23 August 2017 (recruitment) Setting: outpatient, probably national and single centre Country: Iran
Participants	Inclusion criteria: Age over 18 years; no prior history of other urinary system disorders such as urinary tract stones, neurogenic bladder, and urinary infections; no history of underlying diseases such as cirrhosis, renal failure, diabetes, or hypertension; normal levels of urine, fasting blood sugar (FBS), and creatinine; normal results on the first neurological examination of the perineal area, lower limbs, lower limb reflexes, and bulbocavernosus reflex; having weight between 50 to 100 kg; no use of other medicines; no signs of psychological disorders; confirmed diagnosis of chronic prostatitis; creatinine equal to or lower than 1.2 mg; platelet count over 100000/mm3; non‐sensitivity to anti‐epileptic drugs, pregabalin, thiazolidinediones, or other anti‐diabetic agents. Exclusion criteria: Unwillingness to continue the study; major side‐effects due to the use of medications.
Interventions	Intervention group: patients in this group will receive 3mg of melatonin capsules daily for six weeks. Control group: patients in this group will receive 2mg of terazosin tablets (Razak Company) plus 3mg of starch capsules (placebo).
Outcomes	Evaluation and comparison of pain relief, urinary symptoms and side‐effects of medications between two groups, based on the scoring system introduced by the National Institute of Health‐Chronic Prostatitis Symptom Index (NIH‐CPSI) and global response assessment (GRA) two, four and six weeks after intervention.
Starting date	22 August 2016
Contact information	Contact information: m‐jiriaie@mscstu.scu.ac.ir (Ali Serous)
Notes	Funding source: Vice Chancellor for Research of Arak University of Medical Sciences Data extracted from clinical trial registry: IRCT2016071025507N4

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NCT03946163.

Trial name or title	The Effect of Cinnamon on Patients With Chronic Prostatitis/Chronic Pelvic Pain Syndrome; a Pilot Study
Methods	Study design: randomised parallel controlled trial Study dates: 01 January 2017 to 30 June 2018 Setting: outpatient, national/multicentre Country: China
Participants	Inclusion Criteria: Have symptoms of chronic prostatitis / chronic pelvic pain syndrome Duration of symptoms more than 6 months Exclusion Criteria: Positive urine culture or positive prostatic secretions culture Food allergies Previous transurethral intervention, Uncontrolled medical disease (such as diabetes, hypertension or asthma), Use of analgesics for other conditions (like musculoskeletal pain or so)
Interventions	Experimental: Each patient will receive sixty capsules, each capsule contained 1gm of cinnamon bark powder and instructed to use it twice daily for one month Placebo Comparator: Each patient will receive sixty capsules, each capsule contained placebo and instructed to use it twice daily for one month
Outcomes	Prostatitis symptoms Primary Outcome Measures: positive response [Time Frame: 1 month] A reduction in the NIH‐CPSI score of 6 or more points from the initial score  Secondary Outcome Measures: minor positive response [Time Frame: 1 month] A reduction in one or more the sub‐scores of the NIH‐CPSI
Starting date	February 1, 2018 Completion date: June 30, 2019 (study results not available)
Contact information	Principal Investigator: Tawfik J Al‐Marzooq, F.I.C.M.S.  Principal Investigator: Qays A Al‐Timimy, F.I.C.M.S.  Study Director: Harth M Kamber, F.I.C.M.S.  Principal Investigator: Malath A Hussein, F.I.C.M.S.  Principal Investigator: Ahmed A Marzouq, F.I.C.M.S.
Notes	We classified this study as "ongoing" since it was only recently completed.

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Differences between protocol and review

Authors

We incorporated three additional authors who helped in the process of developing and writing this review.

Background and methods: interventions

We added more information about the included interventions in the 'Description of the intervention,' 'How the intervention might work' (Background) and the 'Type of interventions' (Methods). We deleted 'Clinical phenotyping' as an intervention in the Methods section. We moved 'pregabalin' to other pharmacological interventions and renamed the item 'anti‐inflammatories' in order to group NSAIDs and corticosteroids.

Outcomes

For clarity and a better understanding of the review and 'Summary of findings' tables, we renamed the 'Effectiveness of treatment' outcome to 'Prostatitis symptoms' and we specified the threshold for minimal clinically important differences (MCIDs) for each outcome. This did not affect the assessment of the outcomes of the included studies, since we have not changed their definition, but provided more clarity and transparency to the assessments. We included the response rate, defined as the number of participants achieving a MCID. We changed the order of the secondary outcomes and placed 'urinary symptoms' at the end, since we had not planned to included it in the SoF tables.

Data collection and analysis

We added an additional table to summarise the 'Characteristics of the included studies' for participants and interventions.

We added information about how we retrieved data from graphics (PlotDigitalizer).

We deleted the Methods section about time‐to‐event data, since this type of information was not summarised in our review.

Due to the scarcity of data, we could not perform subgroup or sensitivity analysis except in the selected cases specified in the review.

We added the clarification "in at least one domain" for the sensitivity analysis of studies according to risk of bias.

We removed the sensitivity analysis 'Explore the impact of re‐expressing symptom severity as a dichotomous outcome', since we aimed to incorporate the dichotomous data of 'responders' for prostatitis symptoms, which itself did not constitute a sensitivity analysis. We removed the mention of 'number of sessions', since it did not apply to pharmacological interventions.

As suggested by a peer reviewer, we added a sensitivity analysis taking into consideration the changes in the diagnostic criteria for CP/CPPS.

In view of the considerable heterogeneity across studies, we incorporated a predefined comparison as a subgroup analysis: 'Presence of combined therapy due to the presence of co‐interventions: e.g. alpha blockers versus placebo, compared to alpha blockers + co‐interventions (antibiotics and/or analgesics) versus co‐interventions alone or in combination with placebo'.

GRADE methods

We included an optimal information size (OIS) definition based on the predefined criteria for MCID for 'Prostatitis symptoms' measured by NIH‐CPSI score for the assessment of imprecision. For dichotomous outcomes and other continuous outcomes, we assessed the number of events and confidence intervals comparing them to the MCIDs.

We added a reference on how we translated the findings from GRADE to the Plain language summary.

Contributions of authors

Juan VA Franco (JVAF): wrote the protocol, coordinated and performed all the tasks related to the review and wrote the full review.

Tarek Turk (TT): contributed to the Methods section of the protocol, selected studies, extracted data and assessed risks of bias.

Yu‐Tian Xiao (YX): retrieved studies, translated studies in Chinese, selected studies, extracted data and assessed risks of bias.

Stanislav Iakhno (SI): retrieved studies, translated studies in Russian, assessed for eligibility, selected studies, extracted data and assessed risks of bias.

Jae Hung Jung (JHJ): retrieved studies, translated studies in Korean, selected studies, extracted data, assessed risks of bias, performed the GRADE assessments and provided clinical input in the conclusions.

Virginia Garrote (VG): designed the search strategies and wrote the Search methods for identification of studies section, ran the searches and retrieved the included studies.

Federico Ignacio Tirapegui (FIT): provided clinical input and contributed to the data extraction.

Valeria Vietto (VV): contributed to the Methods section of the protocol, selected studies, extracted data and assessed risks of bias and performed the GRADE assessments.

Sources of support

Internal sources

Instituto Universitario Hospital Italiano (IUHI), Argentina.

JVAF is the Cochrane Center Coordinator and VG is the Head Librarian; they both receive a salary from the IUHI.
Hospital Italiano de Buenos Aires, Argentina.

16º Beca del Consejo de Investigación del Hospital Italiano de Buenos Aires

External sources

No sources of support supplied

Declarations of interest

JVAF: none known.

TT: none known.

YX: none known.

SI: none known.

JHJ: none known.

FIT: none known.

VG: none known.

VV: none known.

New

References

References to studies included in this review

Abdalla 2018 {published data only}

Abdalla AE, Hamdy D, Aref M, Mohamrd N, Gamal R, Mohamrd H. PD62‐01 Daily low dose tadalafil in treatment of chronic prostatitis/chronic pelvic pain syndrome: randomized controlled study of efficacy and safety. Journal of Urology 2018;199(4):e1157. [Google Scholar]

Alexander 2004 {published data only}

Alexander RB, Propert KJ, Schaeffer AJ, Landis JR, Nickel JC, O'Leary MP, et al. Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome: a randomized, double‐blind trial. Annals of Internal Medicine 2004;141(8):581‐9. [PUBMED: 15492337] [DOI] [PubMed] [Google Scholar]
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Apolikhin OI, Aliaev IG, Sivkov AV, Vinarov AZ, Oshchepkov VN, Keshishev NG, et al. A comparative clinical randomized trial of cernilton efficacy and safety in patients with chronic abacterial prostatitis. Urologiia 2010;1:29‐34. [PubMed] [Google Scholar]
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Bates 2007 {published data only}

Bates SM, Hill VA, Anderson JB, Chapple CR, Spence R, Ryan C, 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. British Journal of Urology 2007;99(2):355‐9. [DOI] [PubMed] [Google Scholar]

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Cai T, Wagenlehner FM, Luciani LG, Tiscione D, Malossini G, Verze P, et al. Pollen extract in association with vitamins provides early pain relief in patients affected by chronic prostatitis/chronic pelvic pain syndrome. Experimental and Therapeutic Medicine 2014;8(4):1032‐8. [DOI] [PMC free article] [PubMed] [Google Scholar]

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Cha WH, Kim KH, Seo YJ. Comparison of the efficacy of a terpene mixture and alpha‐blocker for treatment of category III chronic prostatitis/chronic pelvic pain syndrome: A prospective study. Korean Journal of Urology 2009;50(2):148‐53. [Google Scholar]

Cheah 2003 {published data only}

Cheah PY, Liong ML, Yuen KH, Teh CL, Khor T, Yang JR, et al. Initial, long‐term, and durable responses to terazosin, placebo, or other therapies for chronic prostatitis/chronic pelvic pain syndrome. Urology 2004;64(5):881‐6. [DOI] [PubMed] [Google Scholar]
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Chen DN, Chen WT, Ma QH, Qin Z, Huang ZW. Qiantongding Decoction: An efficacious therapeutic for type III B prostatitis. Zhonghua Nan Ke Xue 2009;15(1):89‐91. [PubMed] [Google Scholar]

Chen 2011 {published data only}

Chen Y, Wu X, Liu J, Tang W, Zhao T, Zhang J. Effects of a 6‐month course of tamsulosin for chronic prostatitis/chronic pelvic pain syndrome: a multicenter, randomized trial. World J Urol 2011;29(3):381‐5. [DOI] [PubMed] [Google Scholar]

Cheng 2010 {published data only}

Cheng C‐H, Lai Y‐W, Hsueh T‐Y, Chiu Y‐C, Chen S‐S, Lu S‐H, et al. The efficacy of levofloxacin or ciprofloxacin in the management of chronic non‐bacterial prostatitis. International Journal of Urology 2010;17:A335. [Google Scholar]
Lai Y, Cheng C, Hsueh T, Chiu Y, Chen S, Chiu A. The efficacy of levofloxacin or ciprofloxacin in management of chronic non‐bacterial prostatitis. Urology 2012;80(3):S154. [Google Scholar]

Choe 2014 {published data only}

Choe HS, Lee SJ, Han CH, Shim BS, Cho YH. Clinical efficacy of roxithromycin in men with chronic prostatitis/chronic pelvic pain syndrome in comparison with ciprofloxacin and aceclofenac: a prospective, randomized, multicenter pilot trial. Journal of Infection and Chemotherapy 2014;20(1):20‐5. [DOI] [PubMed] [Google Scholar]

Churakov 2012 {published data only}

Churakov AA, Kolesnikov AI, Bliumberg BI, Popkov VM. Cytoflavin in the treatment of patients with chronic abacterial prostatitis and erectile dysfunction. Urologiia 2012;5:64‐6, 68. [PubMed] [Google Scholar]

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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. [DOI] [PubMed] [Google Scholar]
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References to studies excluded from this review

Abdel‐Meguid 2018 {published data only}

Abdel‐Meguid TA, Mosli HA, Farsi H, Alsayyad A, Tayib A, Sait M, et al. Treatment of refractory category III nonbacterial chronic prostatitis/chronic pelvic pain syndrome with intraprostatic injection of onabotulinumtoxinA: a prospective controlled study. The Canadian journal of urology 2018;25(2):9273‐80. [PUBMED: 29680006] [PubMed] [Google Scholar]

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Chen CQ, Yi QT, Chen CH, Gong M. Effect of Interventions for Premature Ejaculation in the Treatment of Chronic Prostatitis with Secondary Premature Ejaculation. Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 2016;38(4):393‐8. [PUBMED: 27594150] [DOI] [PubMed] [Google Scholar]

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ISRCTN43221600. Pilot study for the evaluation of a combined psycho‐ and physiotherapeutic treatment program for patients with chronic pelvic pain syndrome (CPPS). www.isrctn.com/ISRCTN43221600 (first received 14 March 2016).

Kalinina 2015 {published data only}

Kalinina SN, Koren'kov DG, Fesenko VN, Demidov DA, Tiktinskij NO. Pathogenetic treatment of chronic nonbacterial prostatis complicated by sperm disorders. Urologiia 2015;4(4):64‐6, 68. [PubMed] [Google Scholar]

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NCT00194597. Trial of viagra in men with chronic pelvic pain syndrome Type III. clinicaltrials.gov/ct2/show/NCT00194597 (first received 19 September 2005).

NCT00194623 {published data only}

NCT00194623. Botox as a treatment for chronic male pelvic pain syndrome. clinicaltrials.gov/ct2/show/NCT00194623 (first received 19 September 2005).

NCT00194636 {published data only}

NCT00194636. Effectiveness of sympathetic plexus block on male pelvic pain (prostatitis, prostatodynia). clinicaltrials.gov/ct2/show/NCT00194636 (first received 19 September 2005).

NCT00301405 {published data only}

NCT00301405. Open‐label study of thalidomide for chronic prostatitis/chronic pelvic pain. clinicaltrials.gov/ct2/show/NCT00301405 (first received 10 March 2006).

NCT00464373 {published data only}

NCT00464373. Botulinum toxin type A for the treatment of male chronic pelvic pain syndrome. clinicaltrials.gov/ct2/show/NCT00464373 (first received 23 April 2007).

NCT00529386 {published data only}

NCT00529386. Botox for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). clinicaltrials.gov/ct2/show/NCT00529386 (first received 14 September 2007).

NCT01678911 {published data only}

NCT01678911. Efficacy of Gralise® for chronic pelvic pain. clinicaltrials.gov/ct2/show/NCT01678911 (First received 29 June 2015).

NCT01830829 {published data only}

NCT01830829. JALYN for benign prostatic hyperplasia (BPH) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). clinicaltrials.gov/ct2/show/NCT01830829 (First received 12 April 2013).

NCT02042651 {published data only}

NCT02042651. A sham controlled study of the effects of ultrasonic shockwaves as a treatment for chronic pelvic pain. clinicaltrials.gov/ct2/show/NCT02042651 (first received 23 January 2014).

NCT03500159 {unpublished data only}

NCT03500159. Efficacy and safety of AQX‐1125 in subjects with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). clinicaltrials.gov/ct2/show/NCT03500159 (first received 17 April 2018).

Nickel 2011b {published data only}

Nickel JC, Roehrborn C, Montorsi F, Wilson TH, Rittmaster RS. Dutasteride reduces prostatitis symptoms compared with placebo in men enrolled in the REDUCE study. Journal of Urology 2011;186(4):1313‐8. [DOI] [PubMed] [Google Scholar]

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Thin RN, Simmons PD. Review of results of four regimens for treatment of chronic non‐bacterial prostatitis. British Journal of Urology 1983;55(5):519‐21. [DOI] [PubMed] [Google Scholar]

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Tkachuk V N, Al'‐Shukri S K h, Tkacuk I N, Kornienko V I. [Correction of erectile dysfunction in patients with chronic abacterial prostatitis]. Urologiia 2011;‐(6):29‐31. [PubMed] [Google Scholar]

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References to studies awaiting assessment

EUCTR2005‐001849‐42‐IT {published data only}

EUCTR2005‐001849‐42‐IT. A randomized, double blind, placebo controlled, parallel group study to determine the effect of BXL628 in patients with Chronic Non‐Bacterial Prostatitis category III Chronic Pelvic Pain Syndrome, CP/CPPS. www.clinicaltrialsregister.eu/ctr‐search/trial/2005‐001849‐42/IT (first received 20 December 2005).

ISRCTN46815629 {published data only}

ISRCTN46815629. A randomised placebo‐controlled study of tamsulosin, voltarol and the combination in types IIIa and IIIb prostatitis using the newly developed and validated National Institutes of Health (NIH) symptom score. www.isrctn.com/ISRCTN46815629 (date received 12 September 2003).

Kulchavenya 2018 {published data only}

Kulchavenya EV, Shvetsova OP, Breusov AA. [Rationale of use and effectiveness of Longidaza in patients with chronic prostatitis]. Urologiia (Moscow, Russia : 1999) 2018;.(4):64‐71. [PUBMED: 30761792] [PubMed] [Google Scholar]

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NCT00913315 {published data only}

NCT00913315. Efficacy study of tamsulosin and tolterodine treatment for chronic prostatitis. clinicaltrials.gov/ct2/show/NCT00913315 (first received 04 June 2009).

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NCT02385266. Treating urological chronic pelvic pain syndrome (UCPPS) Pain. clinicaltrials.gov/ct2/show/NCT02385266 (first received 11 March 2015).

References to ongoing studies

ChiCTR‐IPR‐16010196 {published data only}

ChiCTR‐IPR‐16010196. Effect of saw palmetto extract in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS): a multicenter, randomized, double‐blind, placebo‐controlled trial; Peking University First Hospital. www.chictr.org.cn/showprojen.aspx?proj=17369 2016.

IRCT2016022225507N2 {unpublished data only}

IRCT2016022225507N2. Effectiveness of pregabalin as an adjuvant therapy for chronic nonbacterial prostatitis. http://en.irct.ir/trial/21322 (Date of registration: 2016‐03‐01).

IRCT2016071025507N4 {unpublished data only}

IRCT2016071025507N4. A clinical trial to comparison the effectiveness of melatonin and capsules containing starch (placebo) as an adjuvant therapy to control symptoms of chronic nonbacterial prostatitis patients. http://en.irct.ir/trial/21324 (Registration date: 2016‐07‐19).

NCT03946163 {unpublished data only}

NCT03946163. The Effect of Cinnamon on Patients With Chronic Prostatitis/Chronic Pelvic Pain Syndrome; a Pilot Study. https://clinicaltrials.gov/ct2/show/NCT03946163 (First posted May 10, 2019).

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PERMALINK

Pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome

Juan VA Franco

Tarek Turk

Jae Hung Jung

Yu‐Tian Xiao

Stanislav Iakhno

Federico Ignacio Tirapegui

Virginia Garrote

Valeria Vietto

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Background

Description of the condition

Description of the intervention

Pharmacological interventions:

Non‐pharmacological interventions:

Multimodal approaches:

Adverse effects

How the intervention might work

Pharmacological interventions

Non‐pharmacological interventions

Clinical phenotyping

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Pharmacological interventions:

Multimodal approaches:

Comparator interventions

Comparisons

Types of outcome measures

Primary outcomes

Secondary outcomes

Method and timing of outcome measurement

Prostatitis symptoms

Adverse events

Sexual dysfunction

Quality of life

Depression and anxiety

Urinary symptoms

Main outcomes for 'Summary of findings' tables

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

1. Description of the interventions by study.

2. Description of studies.

Dealing with duplicate and companion publications

Assessment of risk of bias in included studies

Measures of treatment effect

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

'Summary of findings' tables

Results

Description of studies

Results of the search

1.

Included studies

Design

Sample sizes

Setting