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Base de datos Cochrane de Revisiones Sistemáticas Revisión - Intervención

Intervenciones farmacológicas para el tratamiento del síndrome de dolor pelviano crónico/prostatitis crónica

Declaraciones de intereses de los autores

Versión publicada: 06 octubre 2019 Historial de versiones

https://doi.org/10.1002/14651858.CD012552.pub2
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Antecedentes

El síndrome de dolor pelviano crónico/prostatitis crónica (SDPC/PC) es un trastorno común en el que las dos características clínicas principales son el dolor pelviano y los síntomas de las vías urinarias inferiores. En la actualidad hay muchos enfoques para su tratamiento, tanto mediante intervenciones farmacológicas como no farmacológicas. La puntuación del National Institute of Health ‐ Chronic Prostatitis Symptom Index (NIH‐CPSI) es una medida validada usada comúnmente para medir los síntomas del SDPC/PC. Se consideró una disminución del 25% de la puntuación inicial del NIH‐CPSI o una reducción de seis puntos como DMCI.

Objetivos

Evaluar los efectos de las terapias farmacológicas para el síndrome de dolor pelviano crónico/prostatitis crónica.

Métodos de búsqueda

Se realizó una búsqueda exhaustiva mediante CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, registros de ensayos, literatura gris y resúmenes de congresos, sin restricciones en el idioma de publicación ni en el estado de la publicación. La fecha de la última búsqueda para todas las bases de datos fue julio 2019.

Criterios de selección

Se incluyeron ensayos controlados aleatorizados. Los criterios de inclusión fueron los hombres con un diagnóstico de SDPC/PC. Se incluyeron todas las intervenciones farmacológicas disponibles en comparación con placebo o en comparaciones directas.

Obtención y análisis de los datos

Dos autores de la revisión, de forma independiente, evaluaron la elegibilidad de los estudios, extrajeron los datos y evaluaron el riesgo de sesgo de los estudios incluidos. La calidad de la evidencia (CdE) se evaluó según los criterios GRADE.

Resultados principales

Se incluyeron 99 estudios únicos en 9119 hombres con SDPC/PC, con evaluaciones de 16 tipos de intervenciones farmacológicas. A menos que se indicara lo contrario, las comparaciones se basaron en el seguimiento a corto plazo (menos de 12 meses). La mayoría de los estudios no especificaron las fuentes de financiamiento; 21 estudios informaron sobre el financiamiento de compañías farmacéuticas.

1. Alfabloqueantes: (24 estudios, 2061 participantes). No se conocen con certeza los efectos de estos fármacos sobre los síntomas de prostatitis en comparación con placebo al momento del seguimiento a corto plazo (diferencia de medias [DM] en la puntuación total del NIH‐CPSI ‐5,01; intervalo de confianza [IC] del 95%: ‐7,41 a ‐2,61; 18 estudios, 1524 participantes, CdE muy baja) y al momento del seguimiento a largo plazo (DM ‐5,60; IC del 95%: ‐10,89 a ‐0,32; cuatro estudios, 235 participantes, CdE muy baja). Los alfabloqueantes pueden asociarse con una mayor incidencia de eventos adversos, como mareos e hipotensión postural (cociente de riesgos [CR] 1,60; IC del 95%: 1,09 a 2,34; 19 estudios, 1588 participantes; CdE baja). Los alfabloqueantes probablemente producen poca o ninguna diferencia en la disfunción sexual, la calidad de vida y la ansiedad y la depresión (CdE de moderada a baja).

2. Inhibidores de la 5‐alfa reductasa (5‐ARI): (2 estudios, 177 participantes). La finasterida probablemente reduce los síntomas de prostatitis en comparación con placebo (puntuación del NIH‐CPSI, DM ‐4,60; IC del 95%: ‐5,43 a ‐3,77; un estudio, 64 participantes; CdE moderada) y puede no estar asociada con una mayor incidencia de eventos adversos (CdE baja). No hubo información sobre la disfunción sexual, la calidad de vida ni sobre la ansiedad y la depresión.

3. Antibióticos: (6 estudios, 693 participantes). Los antibióticos (quinolonas) pueden reducir los síntomas de prostatitis en comparación con placebo (puntuación del NIH‐CPSI, DM ‐2,43; IC del 95%: ‐4,72 a ‐0,15; 5 estudios, 372 participantes; CdE baja) y probablemente no se asocian con una mayor incidencia de eventos adversos (CdE moderada). Los antibióticos probablemente producen poca o ninguna diferencia en la disfunción sexual y la calidad de vida (CdE moderada). No hubo información sobre la ansiedad o la depresión.

4. Antiinflamatorios: (siete estudios, 585 participantes). Los antiinflamatorios pueden reducir los síntomas de prostatitis en comparación con placebo (puntuaciones del NIH‐CPSI, DM ‐2,50; IC del 95%: ‐3,74 a ‐1,26; 7 estudios, 585 participantes; CdE baja) y pueden no estar asociados con una mayor incidencia de eventos adversos (CdE baja). No hubo información sobre la disfunción sexual, la calidad de vida ni sobre la ansiedad y la depresión.

5. Fitoterapia: (siete estudios, 551 participantes). La fitoterapia puede reducir los síntomas de prostatitis en comparación con placebo (puntuaciones del NIH‐CPSI, DM ‐5,02; IC del 95%: ‐6,81 a ‐3,23; 5 estudios, 320 participantes; CdE baja) y puede no estar asociada con una mayor incidencia de eventos adversos (CdE baja). Es posible que la fitoterapia no mejore la disfunción sexual (CdE baja). No hubo información sobre la calidad de vida ni sobre la ansiedad y la depresión.

6. Toxina botulínica A (TBA): La inyección intraprostática de TBA (1 estudio, 60 participantes) puede causar una gran reducción de los síntomas de prostatitis (puntuaciones del NIH‐CPSI, DM ‐25,80; IC del 95%: ‐30,15 a ‐21,45), mientras que la inyección de TBA en el músculo del suelo pelviano (1 estudio, 29 participantes) puede no reducir los síntomas de prostatitis (CdE baja). Ambas comparaciones utilizaron una inyección de placebo. Estas intervenciones pueden no estar asociadas con una mayor incidencia de eventos adversos (CdE baja). No hubo información sobre la disfunción sexual, la calidad de vida ni sobre la ansiedad y la depresión.

7. Alopurinol: (dos estudios, 110 participantes). El alopurinol puede dar lugar a poca o ninguna diferencia en los síntomas de prostatitis y los eventos adversos en comparación con placebo (CdE baja). No hubo información sobre la disfunción sexual, la calidad de vida ni sobre la ansiedad y la depresión.

8. Medicina tradicional china (MTC): (7 estudios, 835 participantes); la MTC puede reducir los síntomas de prostatitis (puntuación del NIH‐CPSI, DM ‐3,13; IC del 95%: ‐4,99 a ‐1,28; CdE baja) y puede no estar asociada con una mayor incidencia de eventos adversos (CdE baja). La MTC probablemente no mejora la disfunción sexual (CdE moderada) y puede no mejorar los síntomas de ansiedad y depresión (CdE baja). No había información sobre la calidad de vida.

Las razones más frecuentes para disminuir la CdE fueron las limitaciones de los estudios, la inconsistencia y la imprecisión. Se encontraron pocos ensayos con comparadores activos.

Conclusiones de los autores

Se encontró evidencia de calidad baja a muy baja de que los alfabloqueantes, los antibióticos, los 5‐ARI, los antiinflamatorios, la fitoterapia, la inyección intraprostática de TBA y la medicina china tradicional pueden causar una reducción de los síntomas de prostatitis sin una mayor incidencia de eventos adversos a corto plazo, excepto por los alfabloqueantes, que pueden estar asociados con un aumento de los eventos adversos leves. Se encontraron pocos ensayos con comparadores activos y poca evidencia de los efectos de estos fármacos sobre la disfunción sexual, la calidad de vida o la ansiedad y la depresión. Los futuros ensayos clínicos deben incluir un informe completo de los métodos, incluido un enmascaramiento adecuado, la evaluación consistente de todos los resultados importantes para los pacientes, los eventos adversos potenciales relacionados con el tratamiento y tamaños de la muestra apropiados.

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Intervención para el tratamiento de la prostatitis crónica y el dolor pelviano crónico en hombres

Pregunta de la revisión

¿Cuáles son los efectos de las terapias farmacológicas en hombres con dolor y malestar prolongado en la zona de la próstata y la pelvis, denominado síndrome de dolor pelviano crónico/prostatitis crónica (SDPC/PC)?

Antecedentes

El SDPC/PC es un trastorno común en el cual los hombres sienten dolor pelviano o tienen síntomas molestos (o ambos) al orinar. Su causa no se conoce y hay muchos tratamientos diferentes para este trastorno.

Características de los estudios

La evidencia se actualizó hasta julio 2019. Se encontraron 96 estudios realizados entre 1983 y 2016 en 8646 pacientes con SDPC/PC, con la evaluación de 16 tipos de intervenciones farmacológicas. Estos tratamientos fueron administrados a los hombres de forma ambulatoria. La mayoría de los estudios no especificaron las fuentes de financiamiento; 21 estudios informaron sobre el financiamiento de compañías farmacéuticas.

Resultados clave

Alfabloqueantes: no existe seguridad en cuanto a los efectos de los alfabloqueantes sobre los síntomas de prostatitis. Los alfabloqueantes pueden aumentar los efectos secundarios, por ejemplo, los mareos y la presión arterial baja. Los alfabloqueantes probablemente producen poca o ninguna diferencia en los problemas sexuales, la calidad de vida o la ansiedad y la depresión.

Inhibidores de la 5‐alfa reductasa (5‐ARI, por sus siglas en inglés): Los 5‐ARI probablemente reducen los síntomas de prostatitis y pueden no estar asociados con más efectos secundarios que los observados en los pacientes que reciben placebo. No hubo información sobre los problemas sexuales, la calidad de vida ni sobre la ansiedad y la depresión.

Antibióticos: los antibióticos pueden reducir los síntomas de prostatitis y probablemente no están asociados con efectos secundarios. Los antibióticos probablemente producen poca o ninguna diferencia en los problemas sexuales y la calidad de vida. No hubo información sobre la ansiedad y la depresión.

Antiinflamatorios: los antiinflamatorios pueden reducir los síntomas de prostatitis y pueden no estar asociados con efectos secundarios. No hubo información sobre los problemas sexuales, la calidad de vida ni sobre la ansiedad y la depresión.

Fitoterapia: la fitoterapia puede reducir los síntomas de prostatitis y puede no estar asociada con efectos secundarios. La fitoterapia puede no mejorar los problemas sexuales. No hubo información sobre la calidad de vida ni sobre la ansiedad y la depresión.

Toxina botulínica A (TBA): la inyección de esta toxina en la próstata puede causar una gran reducción de los síntomas de prostatitis, aunque si se aplica a los músculos de la pelvis, la TBA puede no causar este efecto. Estas inyecciones pueden no estar asociadas con efectos secundarios. No hubo información sobre los problemas sexuales, la calidad de vida ni sobre la ansiedad y la depresión.

Alopurinol: el alopurinol puede producir poca o ninguna diferencia en los síntomas de prostatitis y puede no estar asociado con efectos secundarios. No hubo información sobre los problemas sexuales, la calidad de vida ni sobre la ansiedad y la depresión.

Medicina tradicional china (MTC): La MTC puede reducir los síntomas de prostatitis y puede no estar asociada con efectos secundarios. La MTC probablemente no mejora los problemas sexuales y puede no mejorar los síntomas de ansiedad y depresión. No hubo información sobre la calidad de vida.

Calidad de la evidencia

La calidad de la evidencia fue baja a muy baja en la mayoría de los casos, lo cual significa que hay mucha incertidumbre en cuanto a los resultados. Los problemas más frecuentes detectados en los estudios incluidos fueron el diseño inadecuado, el tamaño de la muestra pequeño y el periodo de seguimiento corto (generalmente 12 semanas).

Conclusiones de los autores

disponible en

Implicaciones para la práctica

Se encontró evidencia de calidad baja a muy baja de que los alfabloqueantes pueden reducir los síntomas de prostatitis sobre la base de una reducción de las puntuaciones NIH‐CPSI superiores a dos (pero inferiores a ocho) con una mayor incidencia de eventos adversos menores como mareos e hipotensión. Otras intervenciones como los antibióticos, los antiinflamatorios, la inyección intraprostática de toxina botulínica A, la medicina china tradicional, la mepartricina y los inhibidores de la fosfodiesterasa pueden causar una reducción de los síntomas de prostatitis sin una mayor incidencia de eventos adversos. La evidencia de calidad moderada indica que la fitoterapia y los inhibidores de la 5‐alfa reductasa probablemente causan una pequeña disminución de los síntomas de prostatitis y pueden no estar asociados con una mayor incidencia de eventos adversos.

La evidencia de calidad moderada a alta indica que las siguientes intervenciones pueden ser ineficaces para la reducción de los síntomas de prostatitis: anticolinérgicos, OM‐89, pentosán, pregabalina. La evidencia de calidad baja indica que el alopurinol, los antidepresivos y el tanezumab pueden ser ineficaces para la reducción de los síntomas de prostatitis.

Con frecuencia se encontraron pocos ensayos con comparadores activos y poca evidencia de los efectos de estos fármacos sobre la disfunción sexual, la calidad de vida o la ansiedad y la depresión.

Sobre la base de la incertidumbre en cuanto a los verdaderos efectos de la amplia variedad de intervenciones disponibles, la selección del agente farmacológico adecuado se puede adaptar en función de diferentes factores como: la necesidad de aliviar un tipo de síntoma predominante, el perfil de seguridad de cada agente, los valores y las preferencias del paciente y otros factores contextuales.

Implicaciones para la investigación

Debido a la calidad baja de la evidencia para la mayoría de las comparaciones y resultados incluidos en esta revisión, se necesita investigación adicional sobre los efectos de algunas de las intervenciones incluidas:

  • los ensayos clínicos futuros deben incluir un informe completo de los métodos para una mayor transparencia con respecto a las posibles fuentes de sesgo. Además, al reconocer la naturaleza subjetiva de los resultados informados por los participantes que son críticos para la toma de decisiones, se justifica el enmascaramiento de estas intervenciones y la provisión de información sobre los métodos utilizados para minimizar el sesgo de deserción;

  • los futuros estudios deben incluir una mayor variedad de resultados, incluida la disfunción sexual, la calidad de vida, y la depresión y la ansiedad debido a que representarían el efecto real de estas intervenciones en los participantes con SDPC/PC. Se necesita un seguimiento a largo plazo, que reconozca la cronicidad de este trastorno. También es fundamental que los estudios informen la incidencia de los eventos adversos para evaluar el beneficio neto de las intervenciones;

  • en condiciones ideales, los estudios deben incluir a más de 74 participantes para reducir la imprecisión de los resultados al considerar los síntomas de prostatitis mediante la puntuación del National Institute of Health ‐ Chronic Prostatitis Symptom Index (NIH‐CPSI). Se necesitan tamaños de la muestra más grandes al evaluar el número de pacientes que responden al tratamiento u otros resultados;

  • considerando la comorbilidad alta de los participantes con SDPC/PC, es importante que los estudios incluyan a participantes con trastornos concomitantes para evaluar los efectos entre subgrupos.

Summary of findings

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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 LOWa,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 LOWa,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 LOWa,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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊕⊝
MODERATEa

‐

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)

⊕⊕⊕⊝
MODERATEa

‐

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)

⊕⊕⊝⊝
LOWa,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

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.

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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)

⊕⊕⊕⊝
MODERATEa

‐

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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊝⊝
LOWa,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

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.

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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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊝⊝
LOWb,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)

⊕⊕⊕⊝
MODERATEc,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)

⊕⊕⊕⊝
MODERATEb

‐

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)

⊕⊕⊕⊝
MODERATEc

‐

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

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.

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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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊝⊝
LOWa,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

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.

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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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊕⊝
MODERATEa

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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊝⊝
LOWa,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

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.

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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)

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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊝⊝
LOWb,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)

⊕⊕⊝⊝
LOWd,e

RR 5.00
(0.25 to 99.95)

Study population

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

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.

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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)

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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊝⊝
LOWb,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

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).

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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)

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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊝⊝
LOWb,c

RR 1.34
(0.22 to 8.02)

Study population

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)

⊕⊕⊕⊝
MODERATEb

‐

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)

⊕⊕⊝⊝
LOWb,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

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.

Antecedentes

disponible en

Descripción de la afección

La prostatitis es un trastorno común que afecta al 1,8% de los hombres en los EE.UU. (Suskind 2013), mientras que entre el 10% y el 14% de los hombres en Europa y los EE.UU. sufren de síntomas similares a los de la prostatitis (Bajpayee 2012). Este problema de salud motiva el uno por ciento de las visitas a los consultorios de atención primaria y el ocho por ciento de las consultas de urología en los Estados Unidos (Collins 1998). Solo entre el 5 y el 10% de los casos de prostatitis tienen un origen bacteriano (Bartoletti 2007; De La Rosette 1993). Este trastorno puede afectar a hombres de todas las edades y orígenes étnicos, aunque es más frecuente en los hombres más jóvenes con una media de edad de aparición a los 42 años de edad (Schaeffer 2002). Las dos características clínicas principales de la prostatitis son el dolor pelviano y los síntomas de las vías urinarias inferiores, aunque hay una gama amplia de cuadros clínicos (Nickel 1999).

La clasificación de los National Institutes of Health (NIH) identifica cuatro tipos de prostatitis (Nickel 1999): los tipos I y II, prostatitis bacteriana aguda y crónica respectivamente; el tipo III, prostatitis crónica/síndrome de dolor pelviano crónico (SDPC/PC); y el tipo IV, prostatitis asintomática. No está claro si el tipo III se puede relacionar en todos los casos con el compromiso prostático (True 1999), por lo cual se utiliza la denominación alternativa (síndrome de dolor pelviano crónico). El SDPC/PC se subclasifica en tipo IIIa (inflamatorio) y tipo IIIb (no inflamatorio) según la presencia de células inflamatorias en las secreciones prostáticas.

El SDPC/PC se define cuando el dolor pelviano está presente durante al menos tres de los seis meses precedentes y no se han detectado otras causas identificables (Nickel 1999). Otros síntomas incluyen dificultades obstructivas o irritativas en la evacuación, dolor al eyacular y hematospermia. Los hombres afectados por el SDPC/PC tienen una calidad de vida significativamente reducida y el nivel de dolor pelviano se asocia firmemente con la disfunción sexual (Trinchieri 2007; Walz 2007). El SDPC/PC se asocia con otros síndromes somáticos funcionales, como el síndrome del colon irritable, la cistitis intersticial, el síndrome de fatiga crónica y la fibromialgia (Rodriguez 2009; Suskind 2013). El diagnóstico por lo general se basa en los antecedentes del paciente, el examen físico, el análisis de orina y la prueba de dos o cuatro vasos (Nickel 2012). Las investigaciones adicionales se realizan cuando se considera el diagnóstico diferencial.

Hay diferentes teorías con respecto a la etiología y la fisiopatología del SDPC/PC, que se presentan a continuación.

  • Infección: se detecta ADN bacteriano en una proporción significativa de los hombres con SDPC/PC (Hou 2012). Los antecedentes de infección de transmisión sexual son más frecuentes en los pacientes con SDPC/PC (Pontari 2005). No obstante, el aislamiento de las bacterias uropatógenas en el líquido prostático es similar a los controles (Nickel 2003a).

  • Inflamación/autoinmunidad: se encuentran concentraciones elevadas de citocinas proinflamatorias (interleucina 1, factor de necrosis tumoral, interferón‐γ) y de actividad autoinmunitaria (respuestas de proliferación de células T a antígenos prostáticos) en hombres que sufren de SDPC/PC y en modelos animales (Pontari 2004).

  • Factores neuropsicológicos: el sistema nervioso central puede estar involucrado a través de varios mecanismos de sensibilización al dolor (Miller 2002; Yang 2003). El aumento de la carga de estrés, la respuesta al estrés, las cogniciones de catastrofización del dolor, el funcionamiento social deficiente y la comorbilidad psiquiátrica (ansiedad y depresión) son factores contribuyentes (Riegel 2014).

  • Se observa la evacuación disinérgica asociada con la hipertrofia del cuello de la vejiga en los pacientes que sufren de SDPC/PC poco receptivo al tratamiento (Dellabella 2006; Hruz 2003). El reflujo urinario intraprostático y el aumento de la presión intraprostática están asociados con la inflamación en el SDPC/PC (Kirby 1982; Mehik 2002).

  • Otras teorías descritas para este trastorno incluyen: anormalidades del eje suprarrenal (Anderson 2008), disfunción de los músculos del suelo pelviano (Hetrick 2006; Shoskes 2008a), atrapamiento de los nervios pélvicos (Antolak 2002), predisposición genética a la inflamación (Shoskes 2002), y estrés oxidativo (Arisan 2006).

Descripción de la intervención

Hay una variedad amplia de intervenciones para el tratamiento del SDPC/PC, y cada una considera un marco fisiopatológico o sintomático diferente. La diversidad de intervenciones disponibles refleja la complejidad del trastorno y lo poco que se sabe acerca de sus determinantes.

El tratamiento del SDPC/PC implica un enfoque multimodal y adaptado (Rees 2015; Shoskes 2008b). Algunas de las estrategias usadas solas o en combinación son las siguientes.

Intervenciones farmacológicas:

  • Alfabloqueantes

  • Inhibidores de la 5‐alfa reductasa

  • Antibioticoterapia (quinolonas, tetraciclinas y otros agentes)

  • Antiinflamatorios (fármacos antiinflamatorios no esteroides [AINE], corticosteroides)

  • Fitoterapia (extracto de polen y bioflavonoides)

  • Toxina botulínica A

  • Alopurinol

  • Medicina tradicional (medicina tradicional china, etc.).

  • Otros agentes farmacológicos (p. ej. pregabalina)

Intervenciones no farmacológicas:

  • Acupuntura y electroacupuntura

  • Termoterapia local

  • Terapia con onda de choque extracorpórea

  • Activación de puntos gatillo miofasciales

  • Biorretroalimentación

  • Apoyo psicológico

  • Cirugía prostática

  • Diversas terapias no farmacológicas

Enfoques multimodales:

  • Tratamiento combinado: alfabloqueantes más antibióticos, antibióticos más analgésicos, etc.

Efectos adversos

Los efectos secundarios comunes de los regímenes farmacológicos incluyen (Brunton 2011) los siguientes:

  • Alfabloqueantes: hipotensión, disfunción eyaculatoria, cefalea, mareos y congestión nasal

  • Inhibidores de la 5‐alfa‐reductasa: disminución de la libido, impotencia, potenciación de la hipotensión (en combinación con alfabloqueantes)

  • Quinolonas: malestar gastrointestinal, cefalea, mareos, erupciones y tendinopatía

  • Tetraciclinas: malestar gastrointestinal, erupciones, pigmentación dental y hepatotoxicidad

  • AINE: edema periférico, erupciones, dispepsia, úlcera péptica y hemorragias, lesión renal y hepática, y mayor riesgo de eventos adversos cardiovasculares

  • Fitoterapia: malestar gastrointestinal y reacciones alérgicas

El efecto secundario más frecuente en las fisioterapias es el empeoramiento del dolor durante o inmediatamente después del procedimiento (Fitzgerald 2013).

De qué manera podría funcionar la intervención

Intervenciones farmacológicas

Los alfabloqueantes reducen el tono simpático autonómico en el cuello vesical y la próstata, lo cual mejora el flujo urinario y los síntomas de las vías urinarias inferiores. Los inhibidores de la 5‐alfa‐reductasa reducen la producción de dihidrotestosterona y, en consecuencia, el tamaño de la glándula prostática dependiente de la estimulación de esta hormona. Lo anterior podría aliviar el dolor y el deterioro en la evacuación (Brunton 2011).

Los AINE son antagonistas de las enzimas ciclooxigenasas (Cox) tipo 1 y 2 y de sus subproductos pro‐inflamatorios (Brunton 2011). En consecuencia, tanto los inhibidores selectivos como no selectivos (Cox‐2) podrían reducir el dolor mediado por la inflamación en el SDPC/PC.

La fitoterapia incluye el uso de extracto de polen y bioflavonoides que parecen tener propiedades antiinflamatorias, que disminuyen la proliferación de células acinosas y la producción de interleucina‐6; el factor de necrosis tumoral α y otras citocinas proinflamatorias (Capodice 2005; Kamijo 2001).

Aunque el SDPC/PC se define cuando no puede identificarse ninguna causa bacteriana, los antibióticos se han usado para tratarlo bajo la asunción de la existencia de una infección oculta o tratada de forma deficiente (Hou 2012).

El alopurinol reduciría las secreciones prostáticas de metabolitos que contienen bases de purina y pirimidina en la orina. Estos metabolitos podrían ser causantes de la inflamación prostática a través del reflujo urinario (McNaughton 2002).

La toxina botulínica A tiene propiedades de denervación y también causa la reducción de los mediadores del dolor cuando se la aplica a la próstata en los modelos animales. También causa la apoptosis y la involución de la glándula prostática (Chuang 2006).

Intervenciones no farmacológicas

La acupuntura se dirige a puntos cutáneos específicos que representan diversos órganos internos mediante la inserción de agujas finas y a veces el agregado de corriente eléctrica para aumentar la estimulación (electroacupuntura). En los modelos animales, la electroacupuntura tiene propiedades antiinflamatorias y activa los neurotransmisores analgésicos (Kim 2006).

La hipertermia inducida localmente, mediante procedimientos transrectales o transuretrales, podría disminuir los radicales libres de oxígeno asociados con la inflamación prostática (Gao 2012).

La activación de puntos gatillo miofasciales se dirige a la disfunción de la musculatura del suelo pelviano como una causa potencial o un contribuyente del SDPC/PC (Fitzgerald 2013). La biorretroalimentación también se dirige al músculo del suelo pelviano mediante la contracción inicial para lograr la relajación adicional (Capodice 2005).

Se ha sugerido que los tratamientos psicológicos podrían ser útiles en todos los tipos de síndromes de dolor crónico y la comorbilidad psiquiátrica asociada con el trastorno (p.ej. depresión secundaria al dolor crónico) (Riegel 2014).

Fenotipificación clínica

La fenotipificación clínica es una estrategia que se desarrolló para ofrecer un tratamiento personalizado en un marco etiológico (Shoskes 2008b). El sistema UPOINT considera seis dominios: los síntomas urinarios, la disfunción psicosocial, los hallazgos orgánicos específicos, la infección, la disfunción neurológica y la sensibilidad muscular (Urinary symptoms, Psychosocial dysfunction, Organ‐specific findings, Infection, Neurological dysfunction and Tenderness of muscles), y ofrece un enfoque algorítmico para el uso de las diversas intervenciones disponibles. El número de dominios afectados posee una correlación significativa con la puntuación de los síntomas de prostatitis y el agregado de un dominio de disfunción sexual (Sexual dysfunction, UPOINT[s]) mejora la exactitud en la estratificación de la gravedad de los síntomas (Magri 2010). Aunque en sí no es una intervención, sirve de herramienta de detección para seleccionar la intervención más apropiada para cada paciente.

Por qué es importante realizar esta revisión

El Grupo Cochrane de Urología realizó un ejercicio extenso de asignación de prioridades para identificar una cartera central de los títulos clínicamente más importantes. Este título fue identificado como una prioridad clínicamente importante por el panel de expertos en urología para el desarrollo, el mantenimiento y la inversión de recursos por parte de la base editorial.

El SDPC/PC es una afección prevalente entre los hombres y causa un deterioro significativo de la calidad de vida. Hubo una revisión Cochrane anterior sobre el mismo tema pero con un enfoque metodológico diferente (McNaughton Collins 1999). En años anteriores también se realizaron otras revisiones sistemáticas no relacionadas con Cochrane: algunas de ellas se centraron en intervenciones individuales (Qin 2016; Yang 2006; Zhu 2014), mientras que otras tuvieron un alcance más amplio en cuanto a las intervenciones (Anothaisintawee 2011; Cohen 2012; Magistro 2016). Se consideró necesaria una Revisión Cochrane nueva y actualizada para resumir críticamente el cúmulo de evidencia sobre este trastorno complejo mediante el enfoque GRADE, y así proporcionar información clave acerca del mejor cálculo de la magnitud del efecto en términos relativos y diferencias absolutas para los resultados importantes para los pacientes. Las revisiones sistemáticas anteriores no usaron este enfoque y tuvieron una adherencia variable a la metodología rigurosa recomendada por Cochrane.

El protocolo para esta revisión se publicó por primera vez en agosto de 2016 con el título Intervenciones para el tratamiento del síndrome de dolor pelviano crónico/prostatitis crónica (Franco 2017). Debido a la recuperación de una cantidad significativa de estudios incluidos, el equipo de revisión y el Grupo Cochrane de Urología decidieron dividir la revisión en dos revisiones definidas más exhaustivamente: Intervenciones no farmacológicas para el tratamiento del síndrome de dolor pelviano crónico/prostatitis crónica (Franco 2018) e Intervenciones farmacológicas para el tratamiento del síndrome de dolor pelviano crónico/prostatitis crónica.

Objetivos

disponible en

Evaluar los efectos de las terapias farmacológicas para el síndrome de dolor pelviano crónico/prostatitis crónica.

Métodos

disponible en

Criterios de inclusión de estudios para esta revisión

Tipos de estudios

Se incluyeron ensayos controlados aleatorizados (ECA). Se incluyeron estudios independientemente de su estado de publicación o el idioma de publicación.

Tipos de participantes

Se incluyó a pacientes hombres de todas las edades, independientemente de su condición social u origen étnico, que sufrían de prostatitis crónica/síndrome de dolor pelviano crónico (SDPC/PC), de acuerdo con la clasificación de prostatitis tipo III de los NIH.

Cuando se identificaron estudios en los cuales solo un subgrupo de participantes era relevante para la revisión, se los incluyó cuando había datos disponibles por separado para el subgrupo relevante.

Tipos de intervenciones

Se programó investigar las siguientes comparaciones de la intervención experimental versus la intervención de comparación. Las intervenciones concomitantes debían ser las mismas en los grupos de intervención y de comparación, para establecer comparaciones justas. Se realizó una búsqueda bibliográfica exhaustiva basada en el trastorno para encontrar todas las intervenciones examinadas hasta el momento para el SDPC/PC; por lo tanto, es posible que algunas de ellas no estén incluidas en esta sección.

Intervenciones farmacológicas:

  • Alfabloqueantes

  • Inhibidores de la 5‐alfa reductasa

  • Antibioticoterapia (quinolonas, tetraciclinas y otros agentes)

  • Antiinflamatorios (fármacos antiinflamatorios no esteroides [AINE], corticosteroides)

  • Fitoterapia (extracto de polen y bioflavonoides)

  • Toxina botulínica A

  • Alopurinol

  • Medicina tradicional (medicina tradicional china, etc.).

  • Otros agentes farmacológicos

Enfoques multimodales:

  • Tratamiento farmacológico combinado: por ejemplo, alfabloqueantes más antibióticos, antibióticos más analgésicos, etc.

Intervenciones de comparación

  • Placebo

  • Ningún tratamiento

  • Otros tipos de intervenciones farmacológicas

Comparaciones

Se realizan comparaciones directas o comparaciones de intervención versus placebo/ningún tratamiento. Los tratamientos farmacológicos se comparan por fármaco y por clase. Por ejemplo:

  • Alfabloqueantes versus placebo

  • Alfabloqueantes más quinolonas versus placebo

Y también

  • Tamsulosina versus placebo

  • Tamsulosina más ciprofloxacina versus placebo

No se incluyeron en esta revisión los estudios que evalúan la comparación entre las intervenciones farmacológicas y no farmacológicas, y los que combinan intervenciones no farmacológicas y farmacológicas en el mismo brazo, con objeto de evitar la superposición con la revisión Intervenciones no farmacológicas para el tratamiento de la prostatitis crónica/síndrome de dolor pelviano crónico (Franco 2018).

Tipos de medida de resultado

En esta revisión, no se utilizó la medición de los resultados evaluados como criterio de elegibilidad.

Resultados primarios

  • Síntomas de prostatitis

  • Eventos adversos.

Resultados secundarios

  • Disfunción sexual

  • Calidad de vida (CdV)

  • Depresión y ansiedad

  • Síntomas urinarios

Método y momento adecuado de la medición de los resultados

Se usó la diferencia de importancia clínica para los resultados de revisión, a fin de valorar la calidad de la evidencia en las tablas de "Resumen de resultados" (Johnston 2010). Cuando la diferencia de medias (DM) o el cociente de riesgos (CR) fue igual o mayor que la diferencia mínima clínicamente importante (DMCI), se asumió que muchos participantes podrían haber obtenido una mejoría clínicamente significativa con el tratamiento; cuando la DM era al menos la mitad de la DMCI pero menor que la DMCI, un número apreciable de participantes probablemente había logrado una mejoría clínicamente significativa; y cuando la DM era menor que la mitad de la DMCI, era poco probable que un número apreciable de participantes lograra una mejoría clínicamente significativa (Johnston 2010).

Síntomas de prostatitis

  • Medidos con el National Institutes of Health ‐ Chronic Prostatitis Symptom Index (NIH‐CPSI) como mediciones de la puntuación total y de la subpuntuación, de ser posible, y otras escalas validadas.

  • Se consideró una DMCI en la puntuación del NIH‐CPSI como una disminución del 25% o una reducción de seis puntos con respecto al valor inicial (Nickel 2003b). Este umbral se utilizó para medir la «tasa de pacientes que responden al tratamiento» (Cates 2015).

Eventos adversos.

  • Definidos como intolerancia al tratamiento, efectos adversos de las intervenciones en cualquier momento después de que los participantes fueran asignados al azar a los grupos de intervención/comparación

  • No se estableció un umbral para los eventos adversos. Se consideraron las diferencias clínicamente importantes de los eventos adversos anteriores como una reducción del riesgo relativo de al menos un 25% (Guyatt 2011a)

Disfunción sexual

  • Medida con escalas validadas (por ejemplo, International Index of Erectile Function [IIEF])

  • Se consideró que la DMCI en la puntuación del dominio de la función eréctil del IIEF era de cuatro (Rosen 2011). Se planificó el uso de diferentes umbrales de la DMCI en función de la gravedad de la disfunción eréctil, con un umbral de dos para los hombres con disfunción eréctil leve, cinco para los que presentaban disfunción eréctil moderada y siete para la disfunción eréctil grave (Rosen 2011). También se consideró un IIEF‐5 de más de cinco puntos como una DMCI (Spaliviero 2010).

Calidad de vida

  • Evaluada con el Medical Outcomes Study Short Form 12 (SF‐12) u otras escalas validadas

  • Se consideró que la DMCI en la puntuación del componente físico del SF‐12 era de ocho y en la puntuación del componente mental del SF‐12 era de cuatro (Parker 2013)

Depresión y ansiedad

  • Evaluada con el Beck Depression Inventory, State Anxiety Inventory‐Y u otras escalas validadas

  • Se consideró que una DMCI en el Beck Depression Inventory era de 11 y en el State Anxiety Inventory‐Y era de 10 (Button 2015; Corsaletti 2014)

  • Se consideró que la DMCI en la escala Hospital Anxiety and Depression era de 1,6 (Puhan 2008)

Síntomas urinarios

  • Medidos con la International Prostate Symptom Score (IPSS) o la American Urological Association Symptom Score (AUASS)

  • Una mejoría en la puntuación de la IPSS de tres puntos se consideró como una DMCI para evaluar la eficacia y la efectividad comparativa (Barry 1995). Se planificó el uso de diferentes umbrales de DMC I basado en la gravedad de la IPSS, con un umbral de tres para los hombres con sintomatología leve de las vías urinarias inferiores (SLVUI), de cinco para los que presentaban SLVUI moderada y de ocho para los que presentaban SLVUI grave (Barry 1995).

Se consideraron como a corto plazo los resultados medidos hasta 12 meses inclusive tras la asignación al azar y como a largo plazo los medidos después de los 12 meses.

Resultados principales de las tablas de "Resumen de hallazgos"

Se presenta una tabla de "Resumen de los hallazgos" que informa los siguientes resultados enumerados según la prioridad.

  • Síntomas de prostatitis

  • Eventos adversos.

  • Disfunción sexual

  • Calidad de vida

  • Depresión y ansiedad

Métodos de búsqueda para la identificación de los estudios

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.

Búsquedas electrónicas

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.

Búsqueda de otros recursos

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:

Obtención y análisis de los datos

Selección de los estudios

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).

Extracción y manejo de los datos

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 1; Table 2).

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.

Evaluación del riesgo de sesgo de los estudios incluidos

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.

Medidas del efecto del tratamiento

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.

Cuestiones relativas a la unidad de análisis

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).

Manejo de los datos faltantes

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).

Evaluación de la heterogeneidad

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.

Evaluación de los sesgos de notificación

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.

Síntesis de los datos

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.

Análisis de subgrupos e investigación de la heterogeneidad

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).

Análisis de sensibilidad

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.

Figure 1
Study flow diagram.

Study flow diagram.

Included studies

We included 99 studies with 9119 participants (see Characteristics of included studies; Table 1; Table 2).

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 2019Morgia 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.

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.

Figure 2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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

Figure 3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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

Blinding of participants and personnel

Nineteen studies specified an adequate method for the blinding of participants and personnel (Alexander 2004; Bates 2007; Chen 2011; Elist 2006; Falahatkar 2015; Goldmeier 2005; Iwamura 2015; Lacquaniti 1999; Mehik 2003; Nickel 2003b; Nickel 2004b; Nickel 2008; Nickel 2011a; Nickel 2016; Okada 1985; Pontari 2010; Sivkov 2005; Wagenlehner 2009; Wagenlehner 2014). Forty‐four studies did not adequately blind participants or personnel and were deemed at high risk of bias, considering that all outcomes were subjective (Apolikhin 2010; Cai 2014; Cai 2017; Chen 2009; Choe 2014; Erdemir 2010; Giammusso 2017; Giannantoni 2014; Gottsch 2011; Hu 2015; Jeong 2008; Jiang 2009; Kaplan 2004; Kim 2011a; Kim 2011b; Kong 2014; Kulovac 2007; Lee 2006a; Li 2007; Li 2012; Lin 2007; Lu 2004; Macchione 2017; Maurizi 2019; Morgia 2017; Park 2005; Park 2017; Peng 2003; Shi 1994; Singh 2017; Sun 2008; Tan 2009; Tugcu 2006; Tuğcu 2007; Wang 2004; Wang 2016; Wu 2008; Xia 2014; Xu 2000; Ye 2008; Zeng 2004; Zhang 2007; Zhang 2017; Zhao 2019; Zhou 2008). The remaining studies were at unclear risk of bias of blinding of participants and personnel.

Blinding of outcome assessment

All the outcomes for this review were participant‐reported outcomes. Thirty‐five studies reported blinding of participants (outcome assessors) (Alexander 2004; Bates 2007; Breusov 2014; Cheah 2003; Chen 2011; De Rose 2004; Elist 2006; Falahatkar 2015; Goldmeier 2005; Iwamura 2015; Lacquaniti 1999; Lee 2005; Mehik 2003; Morgia 2017; Nickel 2003a; Nickel 2003b; Nickel 2004a; Nickel 2004b; Nickel 2005; Nickel 2008; Nickel 2011a; Nickel 2016; Okada 1985; Persson 1996; Pontari 2010; Shoskes 1999; Sivkov 2005; Turkington 2002; Wagenlehner 2009; Wagenlehner 2014; Wedren 1987; Yang 2009; Ye 2006; Zhao 2009; Ziaee 2006). Thirty‐nine studies did not adequately blind participants (Apolikhin 2010; Cai 2014; Cai 2017; Chen 2009; Choe 2014; Erdemir 2010; Giannantoni 2014; Gottsch 2011; Hu 2015; Jeong 2008; Jiang 2009; Kim 2011a; Kim 2011b; Kulovac 2007; Lee 2006a; Li 2007; Li 2012; Lin 2007; Lu 2004; Macchione 2017; Park 2005; Peng 2003; Shi 1994; Singh 2017; Sun 2008; Tan 2009; Tugcu 2006; Tuğcu 2007; Wang 2004; Wang 2016; Wu 2008; Xia 2014; Xu 2000; Ye 2008; Zeng 2004; Zhang 2007; Zhang 2017; Zhao 2019; Zhou 2008). The remaining studies were at unclear risk of bias of outcome assessment.

Incomplete outcome data

Forty‐three studies specified that outcome data for all outcomes were available in all or nearly all participants (Alexander 2004; Apolikhin 2010; Breusov 2014; Cai 2014; Chen 2009; Chen 2011; Elist 2006; Erdemir 2010; Falahatkar 2015; Gottsch 2011; Hu 2015; Jeong 2008; Jiang 2009; Jung 2006; Kaplan 2004; Kim 2008; Kong 2014; Li 2003; Li 2007; Lin 2007; Maurizi 2019; Morgia 2010; Nickel 2003a; Nickel 2004b; Park 2005; Peng 2003; Pontari 2010; Shi 1994; Singh 2017; Sun 2008; Tan 2009; Wang 2004; Wang 2016; Wu 2008; Xia 2014; Yang 2009; Yang 2010; Ye 2006; Ye 2008; Zeng 2004; Zhao 2009; Zhou 2008; Ziaee 2006). Thirty‐six had unbalanced or high attrition (or both) of outcome data at follow‐up and were deemed at high risk of bias (Bates 2007; Cai 2017; Cavallini 2001; Cheah 2003; De Rose 2004; Dunzendorfer 1983; Goldmeier 2005; Gül 2001; Iwamura 2015; Kim 2003; Kim 2011a; Kim 2011b; Lee 2005; Leskinen 1999; Li 2012; Lu 2004; Mehik 2003; Morgia 2017; Nickel 2003b; Nickel 2004a; Nickel 2005; Nickel 2008; Nickel 2016; Okada 1985; Persson 1996; Shoskes 1999; Sivkov 2005; Tugcu 2006; Turkington 2002; Wagenlehner 2009; Wagenlehner 2014; Wedren 1987; Xu 2000; Zhang 2007; Zhang 2017; Zhao 2019). The remaining studies were at unclear risk of bias in this domain.

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: Summary of findings for the main comparison Alpha blockers compared to placebo for chronic prostatitis/chronic pelvic pain syndrome; Summary of findings 2 5‐alpha reductase inhibitors compared to placebo for chronic prostatitis/chronic pelvic pain syndrome; Summary of findings 3 Antibiotic therapy compared to placebo for chronic prostatitis/chronic pelvic pain syndrome; Summary of findings 4 Anti‐inflammatories compared to control for chronic prostatitis/chronic pelvic pain syndrome; Summary of findings 5 Phytotherapy compared to placebo or other agents for chronic prostatitis/chronic pelvic pain syndrome; Summary of findings 6 Botulinum toxin A compared to placebo for chronic prostatitis/chronic pelvic pain syndrome; Summary of findings 7 Allopurinol compared to placebo for chronic prostatitis/chronic pelvic pain syndrome; Summary of findings 8 Traditional Chinese Medicine compared to placebo or usual care for chronic prostatitis/chronic pelvic pain syndrome

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 1 and Table 2 for further details of the participants and interventions. See summary of findings Table for the main comparison. 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).

Figure 4
Funnel plot of comparison: 1 Alpha‐blockers versus placebo, outcome: 1.1 Prostatitis symptoms: short term.

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)).

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).

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).

1.2. 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.

Figure 5
Funnel plot of comparison: 1 Alpha‐blockers versus placebo, outcome: 1.8 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.

1.4. 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.

1.5. 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).

1.6. 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.

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).

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).

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).

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).

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 1 and Table 2 for further details of the participants and interventions. See summary of findings 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).

2.2. 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. 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 1 and Table 2 for further details of the participants and interventions. See summary of findings 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).

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).

3.2. 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).

3.3. 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.

3.4. 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).

3.5. 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.

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).

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).

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).

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).

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 1 and Table 2 for further details of the participants and interventions. See summary of findings 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).

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).

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.

4.2. 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.

4.3. 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.

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).

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).

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 1 and Table 2 for further details of the participants and interventions. See summary of findings 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).

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.

5.2. 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.

5.3. 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).

5.4. 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.

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).

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).

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 1 and Table 2 for further details of the participants and interventions. See summary of findings 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).

6.1.2. 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).

6.3. 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).

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 1 and Table 2 for further details of the participants and interventions. See summary of findings 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).

7.2. 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 1 and Table 2 for further details of the participants and interventions. See summary of findings 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).

8.2. 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).

8.3. 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.

8.4. 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).

8.6. 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 1 and Table 2 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.

Discusión

disponible en

Resumen de los resultados principales

Se incluyeron 99 estudios únicos con 9119 hombres con prostatitis crónica/síndrome de dolor pelviano crónico (SDPC/PC), con la evaluación de 16 tipos de intervenciones farmacológicas. La mayoría de las comparaciones incluyeron información del seguimiento a corto plazo. La mediana de edad de los participantes fue 38 años.

Comparaciones principales

Se encontró evidencia de calidad baja a muy baja de que los alfabloqueantes pueden reducir los síntomas de prostatitis sobre la base de una reducción de las puntuaciones del NIH‐CPSI de más de dos (pero menos de ocho) con una mayor incidencia de eventos adversos menores como mareos e hipotensión. La evidencia de calidad moderada a baja indica que los inhibidores de la 5‐alfa reductasa, los antibióticos, los antiinflamatorios y la fitoterapia probablemente causan una pequeña disminución de los síntomas de prostatitis y pueden no asociarse con una mayor incidencia de eventos adversos. La inyección intraprostática de TBA puede causar una gran reducción de los síntomas de prostatitis con eventos adversos relacionados con el procedimiento (hematuria), aunque la inyección de TBA en el músculo del suelo pelviano puede no tener los mismos efectos (evidencia de calidad baja). El alopurinol también puede ser ineficaz para la reducción de los síntomas de prostatitis (evidencia de calidad baja). Se evaluó una amplia gama de intervenciones relacionadas con la medicina tradicional china; la evidencia de calidad baja mostró que pueden reducir los síntomas de prostatitis sin una mayor incidencia de eventos adversos.

Otras intervenciones

La evidencia de calidad moderada a alta indica que las siguientes intervenciones pueden ser ineficaces para la reducción de los síntomas de prostatitis: anticolinérgicos, OM‐89, pentosán y pregabalina. La evidencia de calidad baja a muy baja indica que los antidepresivos y el tanezumab pueden ser ineficaces para la reducción de los síntomas de prostatitis. La evidencia de calidad baja indica que la mepartricina y los inhibidores de la fosfodiesterasa pueden reducir los síntomas de prostatitis, sin una mayor incidencia de eventos adversos.

Compleción y aplicabilidad general de las pruebas

La revisión se centró en los hombres con SDPC/PC. Casi todos los estudios incluidos usaron criterios de inclusión consistentes definidos por el NIH (Nyberg 1999). Estos criterios de diagnóstico están relacionados con la práctica clínica, debido a que estos participantes generalmente son examinados para detectar las enfermedades urológicas que podrían imitar el SDPC/PC. Sin embargo, cierto grado de efecto del consenso del NIH en el diagnóstico del SDPC/PC podría haber cambiado la clasificación de los participantes a través del tiempo (Krieger 2002); por lo tanto, los resultados de los ensayos más antiguos deben interpretarse con precaución teniendo en cuenta los criterios de diagnóstico actuales. Se incorporó un análisis de sensibilidad basado en esta consideración.

Se mantuvieron criterios de inclusión abiertos para las intervenciones incluidas. Esta decisión se basó en los determinantes fisiopatológicos poco comprendidos del SDPC/PC (ver Antecedentes). Lo anterior dio lugar a la inclusión de una amplia variedad de intervenciones farmacológicas, lo cual podría relacionarse con la práctica clínica, considerando que, por lo general, los pacientes con SDPC/PC prueban diferentes opciones de tratamiento antes de lograr alguna forma de alivio. Puede haber dificultades en la interpretación de algunas comparaciones directas, debido a que no se conoce la efectividad de cada intervención por separado: por ejemplo, para la comparación del extracto de polen (deprox®) versus bromelaína, puede que no se sepa si el extracto de polen y la bromelaína son superiores al placebo en primer lugar para analizar su efectividad relativa.

La revisión se centró en los resultados críticos de importancia para el paciente; sin embargo, la mayoría de los estudios no los informó de manera consistente, especialmente la incidencia de eventos adversos. Este problema es común en los ensayos clínicos (Ioannidis 2001) y plantea dificultades al calcular el beneficio neto de las intervenciones. Además, la mayoría de los estudios incluidos no informó los efectos de las intervenciones sobre la calidad de vida (CdV), la función sexual y la salud mental, considerando el efecto marcado del SDPC/PC en estos dominios (Krsmanovic 2014). Se reconoce que la puntuación del NIH‐CPSI incluye subpuntuaciones de la CdV y de los síntomas urinarios que, junto con la subpuntuación del dolor, contribuyen a una puntuación total que ha demostrado ser válida y fiable (Litwin 1999; McNaughton Collins 2001; Propert 2006; Turner 2003); sin embargo, estas subpuntuaciones no han sido validadas individualmente para estas construcciones. Se reconoce que las puntuaciones validadas para la CdV, los síntomas urinarios, la disfunción sexual y la ansiedad y la depresión podrían no haber sido validadas en la subpoblación de hombres con SDPC/PC, por lo que sus valores deben interpretarse con cautela, especialmente utilizando la evaluación de la diferencia mínima clínicamente importante (DMCI).

Algunas intervenciones farmacológicas pueden tener diferentes impactos sobre los resultados principales de estos trastornos. Por ejemplo: los inhibidores de la fosfodiesterasa pueden tener un mayor impacto en la disfunción sexual que en los síntomas de prostatitis; los analgésicos solos o en combinación pueden utilizarse más cuando se producen exacerbaciones del dolor. Con este fin, el enfoque UPOINTS permite al médico examinar las características de la persona y sus necesidades para guiar la selección de las intervenciones farmacológicas y no farmacológicas (Magri 2010; Shoskes 2008b). Al considerar los eventos adversos, se enumeraron los que se informan con más frecuencia en los ensayos clínicos. Se reconoce que podría haber una amplia gama de posibles eventos adversos que los ensayos clínicos podrían no haber captado, y que los estudios observacionales podrían proporcionar más información sobre este tema (Singh 2012). La mayoría de los eventos adversos desaparecieron de forma espontánea y tuvieron un impacto menor (p.ej. malestar gastrointestinal). En algunos casos, los autores administraron los fármacos de forma gradual para reducir el impacto de los eventos adversos de inicio temprano, como la hipotensión postural para los alfabloqueantes (Lepor 2007). Además, podrían haberse utilizado otras sugerencias, como ser cauteloso al levantarse de la cama, para evitar este evento adverso (Figueroa 2010). Otros eventos adversos que pueden no ser transitorios (p.ej. eyaculación retrógrada) pueden ser más difíciles de tratar, y puede ser necesaria una discusión con el paciente para obtener la importancia de estos resultados, en especial en relación con la actividad sexual y las expectativas (Lepor 2007). A diferencia de la eyaculación retrógrada inducida por la cirugía, este evento adverso por lo general se revierte cuando se suspenden los alfabloqueantes.

Además, la mayoría de los estudios presentó los resultados a las cuatro a 12 semanas de seguimiento, lo cual podría ser insuficiente considerando que los hombres con SDPC/PC en general tienen grandes antecedentes fluctuantes de síntomas, generalmente durante varios años (Clemens 2015).

Se había planificado explorar el efecto de las intervenciones en subgrupos de hombres con diferentes niveles de gravedad de las enfermedades y en subgrupos de hombres con comorbilidades comunes (Gasperi 2017), aunque los estudios incluidos proporcionaron datos insuficientes al respecto; por tanto, los análisis fueron limitados.

Esta revisión complementa otra revisión Cochrane en la misma área: Intervenciones no farmacológicas para el tratamiento del síndrome de dolor pelviano crónico/prostatitis crónica (Franco 2018). En dicha revisión se destacó que la acupuntura y la terapia extracorpórea por ondas de choque probablemente son beneficiosas para este trastorno. Aunque no se encontró evidencia sobre el apoyo psicológico para esta afección, la psicoterapia (p.ej. la terapia cognitivo‐conductual) ha sido efectiva en el tratamiento de los trastornos somatomorfos (Van Dessel 2014).

Algunos de los tratamientos incluidos para las comparaciones principales expresadas en las tablas de `Resumen de resultados' y en otras secciones de la revisión no han sido parte de la atención habitual para el SDPC/PC, en especial: anticolinérgicos, mepartricina, OM‐89, inhibidores de la fosfodiesterasa, pregabalina y tanezumab. Para apoyar lo anterior, se utilizaron, como ejemplo, las recomendaciones de la European Association of Urology (disponibles en uroweb.org/guideline/chronic‐pelvic‐pain/ [última visita en julio de 2018]). Según declararon los autores de la guía, se debe considerar cuidadosamente la aplicabilidad de estas intervenciones en la práctica diaria. Por ejemplo, la toxina botulínica A puede no ser fácil de conseguir o puede no ser aceptable para la mayoría de los hombres, ya que implica una inyección intraprostática. Como lo establece el GRADE Evidence to Decision Framework, se justifica una evaluación cuidadosa de los valores y preferencias del paciente, del uso de recursos y cuestiones de equidad y de la aceptabilidad y factibilidad de las intervenciones al redactar las recomendaciones de las guías (Alonso‐Coello 2016); lo cual está más allá del alcance de esta revisión.

Calidad de la evidencia

Las limitaciones principales del cúmulo de evidencia fueron las siguientes.

  • Limitaciones de los estudios: la mayoría de los estudios tuvo problemas para ocultar las intervenciones del personal del estudio y de los participantes. Este hecho es particularmente importante para esta revisión considerando que todos los resultados predefinidos fueron subjetivos e informados por los participantes. Muchos estudios tenían una cantidad considerable de datos de resultado faltantes y había pocas explicaciones sobre su tratamiento (p.ej., mediante el uso de métodos como «la última observación realizada»). Además, la mayoría de los estudios informaron de manera deficiente sobre la generación de la secuencia aleatoria y la ocultación de la asignación y la mayoría no había publicado el protocolo ni el plan de análisis para evaluar el riesgo de informe selectivo.

  • Inconsistencia: se encontró heterogeneidad considerable en algunas de las comparaciones principales; no fue posible explicarla mediante los análisis de sensibilidad y de subgrupos predefinidos. Se agregó un análisis de subgrupos basado en una de las condiciones predefinidas, pero ninguno de estos análisis produjo resultados significativos.

  • Imprecisión: se estimó un tamaño de información óptimo de 74 para el resultado primario `síntomas de prostatitis', y casi el 50% de los estudios tuvo un tamaño de la muestra más pequeño; por lo tanto, la mayoría de los estudios presentó imprecisión. No obstante, en algunos casos, el metanálisis de algunos de los estudios incluidos aumentó el número de participantes para cada comparación, superando esta limitación. Lo anterior fue más difícil de lograr para el resultado “eventos adversos” para el cual el número pequeño de eventos (en algunos casos no hubo ninguno) dio lugar a una imprecisión considerable.

  • Sesgo de publicación: se evaluó el riesgo de sesgo de publicación mediante el uso de gráficos en embudo en pocos resultados, debido a la escasez de ensayos, y no se encontró evidencia de ninguna asimetría sugestiva.

Sesgos potenciales en el proceso de revisión

Se siguió estrictamente el protocolo publicado para reducir el riesgo de sesgo en la realización de esta revisión.

Se realizó una búsqueda exhaustiva en bases de datos múltiples, registros de ensayos y otras fuentes para reducir el riesgo del metasesgo en la revisión. No se restringieron las búsquedas ni la inclusión de los estudios sobre la base del idioma de publicación. Treinta y ocho estudios fueron escritos en un idioma diferente al inglés. Se incorporaron tres autores adicionales (JHJ, SI, YX) que ayudaron en el proceso de desarrollo y redacción de esta revisión al leer y procesar los artículos en coreano, ruso y chino. Sin embargo, la evaluación de los estudios individuales fue realizada por un único autor, lo cual podría haber introducido errores en el proceso de desarrollo de los juicios sobre el riesgo de sesgo y la extracción de datos. Se intentó minimizar estos errores mediante el uso de la traducción asistida por computadora y la discusión exhaustiva de los datos extraídos con los coautores.

No fue posible recuperar algunos de los estudios sobre medicina tradicional china (MTC) publicados en algunas revistas chinas (disponibles en la base de datos China National Knowledge Infrastructure) que se incluyeron en otras revisiones que realizaron búsquedas en bases de datos chinas (ver Acuerdos y desacuerdos con otros estudios o revisiones). Si se encuentran los informes de estos estudios, se los evaluará para su inclusión en las actualizaciones de esta revisión, ya que no existe información clara acerca de su elegibilidad. Sin embargo, se observa que los resultados de estos estudios informados en las revisiones correspondientes son consistentes con los hallazgos.

Se estableció contacto con los autores de los estudios en ocasiones múltiples con una tasa de respuesta variable. Sin embargo, se reconoce que muchas de las clasificaciones del riesgo de sesgo de “poco claro” se debieron a las limitaciones en el informe de los estudios, en lugar de a un riesgo cierto de sesgo en la realización de estos ensayos. También se estableció contacto con los autores para obtener los datos de resultado faltantes (p.ej. desviación estándar, número de participantes, valores de P, etc.) con una tasa de respuesta deficiente en la mayoría de los casos. Sin embargo, se informan todos los datos de resultado disponibles en «Estudios no incluidos en el metanálisis» o en la tabla de «Resumen de resultados».

Se suprimió el ítem de “Fenotipificación clínica” como una intervención en la revisión, según lo sugerido por un revisor. Se reconoce que esta estrategia podría no constituir en sí una intervención. Este cambio no afectó los resultados de esta revisión debido a que no se encontró ningún ensayo sobre este tema. También se modificó la presentación de algunos de los métodos de esta revisión (evaluación de los resultados y criterios GRADE), aunque este hecho tampoco afectó los resultados de la revisión (ver Diferencias entre el protocolo y la revisión).

Se intentó explicar las razones de la heterogeneidad estadística entre los estudios para muchas comparaciones, aunque no fue posible hacerlo mediante los análisis de subgrupos predefinidos y post hoc. Lo anterior dio lugar a la disminución de la confianza en la evidencia debido a la inconsistencia, de acuerdo con los criterios GRADE. Se reconoce que existe una gran variabilidad en las causas subyacentes y las manifestaciones clínicas de los hombres que padecen esta afección a través de todos los estudios, por lo que se cree que podría haber otras variables que podrían explicar esta inconsistencia. Debido a que aún no se conoce la causa subyacente del SDPC/PC y puede abarcar diferentes vías patógenas (Appiya 2019), a menos que existan distinciones claras de estas vías y diferentes subtipos de SDPC/PC con factores etiológicos y pronósticos comunes, es de esperar que persistan estas inconsistencias entre las poblaciones de estudio de los diferentes ensayos.

Acuerdos y desacuerdos con otros estudios o revisiones

Se encontraron varias revisiones sistemáticas que consideraron intervenciones para el SDPC/PC. Estas revisiones tuvieron varias limitaciones metodológicas: falta de un protocolo que estableciera los métodos de revisión, búsquedas insuficientemente exhaustivas, restricciones de idioma inadecuadas y ninguna integración de la calidad de la evidencia con los resultados, por ejemplo, mediante el uso de los métodos GRADE.

Revisiones Cochrane

En una revisión Cochrane anterior sobre la pregabalina para el SDPC/PC (Aboumarzouk 2012), los autores incluyeron el mismo ensayo (Pontari 2010) que esta revisión y establecieron conclusiones similares, aunque se consideró que el estudio incluido estaba en riesgo bajo de sesgo, mientras que la revisión anterior lo consideró en riesgo alto de sesgo. Los juicios se justifican en la sección Características de los estudios incluidos. Tres revisiones sistemáticas (dos de ellas revisiones Cochrane) incluyeron intervenciones farmacológicas y no farmacológicas (McNaughton 2000; McNaughton Collins 1999; McNaughton 2002). Se incluyeron algunos de los ensayos cubiertos en estas revisiones. Los hallazgos sobre la efectividad y las limitaciones de la calidad de la evidencia fueron similares, aunque la mayoría de los estudios incluidos fueron anteriores a 1999; cuando el Research Consensus definió los criterios más recientes para esta afección (Nyberg 1999). Por esta razón, se realizó un análisis de sensibilidad para examinar este efecto, tal y como sugirió un revisor de la revisión anterior (Franco 2018).

Otras revisiones

En una revisión exhaustiva, Anothaisintawee 2011 evaluó los efectos de los alfabloqueantes, los antibióticos, los antiinflamatorios, la finasterida, la fitoterapia, el pentosán, la pregabalina y el tratamiento combinado, e incluyó los mismos ensayos que la revisión con resultados similares; sin embargo, esta revisión indicó que "la magnitud del beneficio aparente con los alfabloqueantes puede estar distorsionada por el sesgo de publicación", lo cual no se encontró en la evaluación.

Cai 2017 se centró en los efectos del extracto de polen e incluyó estudios en animales, estudios no aleatorizados y algunos de los ensayos clínicos incluidos en esta revisión, con los mismos resultados. Dos revisiones sistemáticas (Cohen 2012; Yang 2008) incluyeron los ensayos de esta revisión, aunque tuvieron poco poder estadístico para algunas comparaciones, como las que incluyeron antibióticos y antiinflamatorios. Yang 2008 incluyó algunos ensayos solo disponibles en la China National Knowledge Infrastructure (CNKI).

Una revisión sistemática de la MTC para la prostatitis crónica (Chen 2006) incluyó nueve ensayos aleatorizados de la base de datos CNKI, de los cuales ninguno se incluyó en esta revisión. Encontraron que hubo evidencia de calidad baja de que la MTC era equivalente o superior a los tratamientos occidentales, aunque el metanálisis agrupó estudios aleatorizados y no aleatorizados. No está claro si incluyeron a participantes con prostatitis bacteriana.

Erickson 2008 (y su actualización Le 2011) incluyó algunos de los estudios de las intervenciones farmacológicas para el SDPC/PC. Esta revisión indicó que los inhibidores de la 5‐alfa‐reductasa, el alopurinol, los alfabloqueantes, la mepartricina, los AINE, el pentosán y la quercetina pueden tener poco o ningún efecto beneficioso para esta enfermedad, pero con grandes dudas debido a la calidad baja del cúmulo de evidencia. Aunque la mayoría de los resultados de dicha revisión son similares a los de esta revisión, los autores centraron su análisis de los alfabloqueantes en el estudio más grande en riesgo bajo de sesgo. Este hecho concuerda con el análisis de sensibilidad en el que se encontró que los alfabloqueantes son ineficaces. Otras dos revisiones (Lee 2007; Yang 2006) evaluaron el efecto de los alfabloqueantes, aunque sus evaluaciones de la calidad de los estudios fueron limitadas.

Una revisión sistemática con un metanálisis en red (Qin 2016) evaluó los efectos de la acupuntura, los alfabloqueantes, los antibióticos y el tratamiento combinado, e incluyó los mismos ensayos que esta revisión con resultados similares sobre la efectividad. El gráfico de superficie bajo la curva de clasificación acumulativa (SUCRA, por sus siglas en inglés) reveló hallazgos interesantes al comparar los tratamientos no farmacológicos y los tratamientos farmacológicos, a favor de la acupuntura y la electroacupuntura. Otra revisión que utilizó el metanálisis en red (Thakkinstian 2012) también tuvo resultados similares, aunque los autores reflejaron que "los resultados son discrepantes entre los análisis de las puntuaciones de los síntomas y la capacidad de respuesta del tratamiento". Se cree que lo anterior se relaciona con el hecho de que la diferencia de las puntuaciones de los síntomas requieren tamaños de la muestra más pequeños que las mediciones de los efectos del tratamiento para los resultados dicotómicos. Esta es la razón por la cual la calidad de la mayoría de los análisis para los «pacientes que responden al tratamiento» se disminuyó debido a la imprecisión.

Magistro 2016 incluyó ensayos similares pero con un alcance más limitado, y los autores afirmaron que "La comprensión actual de la fisiopatología subyacente del SDPC/PC que resulta en este síndrome altamente variable no habla a favor de una monoterapia para el tratamiento".

Study flow diagram.
Figuras y tablas -
Figure 1

Study flow diagram.

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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figuras y tablas -
Figure 2

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

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Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
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Figure 3

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

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Funnel plot of comparison: 1 Alpha‐blockers versus placebo, outcome: 1.1 Prostatitis symptoms: short term.
Figuras y tablas -
Figure 4

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

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Funnel plot of comparison: 1 Alpha‐blockers versus placebo, outcome: 1.8 Adverse events.
Figuras y tablas -
Figure 5

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

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Comparison 1 Alpha‐blockers versus placebo, Outcome 1 Prostatitis symptoms: short term.
Figuras y tablas -
Analysis 1.1

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

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Comparison 1 Alpha‐blockers versus placebo, Outcome 2 Prostatitis symptoms: pain.
Figuras y tablas -
Analysis 1.2

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

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Comparison 1 Alpha‐blockers versus placebo, Outcome 3 Prostatitis symptoms: urinary.
Figuras y tablas -
Analysis 1.3

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

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Comparison 1 Alpha‐blockers versus placebo, Outcome 4 Prostatitis symptoms: quality of life.
Figuras y tablas -
Analysis 1.4

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

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Comparison 1 Alpha‐blockers versus placebo, Outcome 5 Prostatitis symptoms: responders rate.
Figuras y tablas -
Analysis 1.5

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

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Comparison 1 Alpha‐blockers versus placebo, Outcome 6 Prostatitis symptoms: long term.
Figuras y tablas -
Analysis 1.6

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

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Comparison 1 Alpha‐blockers versus placebo, Outcome 7 Prostatitis symptoms: long term.
Figuras y tablas -
Analysis 1.7

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

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Comparison 1 Alpha‐blockers versus placebo, Outcome 8 Adverse events.
Figuras y tablas -
Analysis 1.8

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

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Comparison 1 Alpha‐blockers versus placebo, Outcome 9 Sexual dysfunction.
Figuras y tablas -
Analysis 1.9

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

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Comparison 1 Alpha‐blockers versus placebo, Outcome 10 Quality of life: mental.
Figuras y tablas -
Analysis 1.10

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

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Comparison 1 Alpha‐blockers versus placebo, Outcome 11 Quality of life: physical.
Figuras y tablas -
Analysis 1.11

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

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Comparison 1 Alpha‐blockers versus placebo, Outcome 12 Anxiety and depression.
Figuras y tablas -
Analysis 1.12

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

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Comparison 1 Alpha‐blockers versus placebo, Outcome 13 Urinary symptoms.
Figuras y tablas -
Analysis 1.13

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

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

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

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Comparison 1 Alpha‐blockers versus placebo, Outcome 15 Adverse events (sensitivity analysis according to risk of bias).
Figuras y tablas -
Analysis 1.15

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

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

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

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Comparison 1 Alpha‐blockers versus placebo, Outcome 17 Adverse events (subgroup analysis by co‐interventions).
Figuras y tablas -
Analysis 1.17

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

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Comparison 2 5 alpha reductase inhibitors versus placebo, Outcome 1 Prostatitis symptoms.
Figuras y tablas -
Analysis 2.1

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

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Comparison 2 5 alpha reductase inhibitors versus placebo, Outcome 2 Prostatitis symptoms: responder rate.
Figuras y tablas -
Analysis 2.2

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

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Comparison 2 5 alpha reductase inhibitors versus placebo, Outcome 3 Adverse events.
Figuras y tablas -
Analysis 2.3

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

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Comparison 3 Antibiotic therapy versus placebo, Outcome 1 Prostatitis symptoms.
Figuras y tablas -
Analysis 3.1

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

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Comparison 3 Antibiotic therapy versus placebo, Outcome 2 Prostatitis symptoms: pain.
Figuras y tablas -
Analysis 3.2

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

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Comparison 3 Antibiotic therapy versus placebo, Outcome 3 Prostatitis symptoms: urinary.
Figuras y tablas -
Analysis 3.3

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

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Comparison 3 Antibiotic therapy versus placebo, Outcome 4 Prostatitis symptoms: quality of life.
Figuras y tablas -
Analysis 3.4

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

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Comparison 3 Antibiotic therapy versus placebo, Outcome 5 Prostatitis symptoms: responder rate.
Figuras y tablas -
Analysis 3.5

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

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Comparison 3 Antibiotic therapy versus placebo, Outcome 6 Adverse events.
Figuras y tablas -
Analysis 3.6

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

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Comparison 3 Antibiotic therapy versus placebo, Outcome 7 Sexual dysfunction.
Figuras y tablas -
Analysis 3.7

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

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Comparison 3 Antibiotic therapy versus placebo, Outcome 8 Quality of life: mental.
Figuras y tablas -
Analysis 3.8

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

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Comparison 3 Antibiotic therapy versus placebo, Outcome 9 Quality of life: physical.
Figuras y tablas -
Analysis 3.9

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

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Comparison 3 Antibiotic therapy versus placebo, Outcome 10 Urinary symptoms.
Figuras y tablas -
Analysis 3.10

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

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Comparison 3 Antibiotic therapy versus placebo, Outcome 11 Prostatitis symptoms: subgroup analysis (age).
Figuras y tablas -
Analysis 3.11

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

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Comparison 3 Antibiotic therapy versus placebo, Outcome 12 Adverse events: subgroup analysis (age).
Figuras y tablas -
Analysis 3.12

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

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Comparison 3 Antibiotic therapy versus placebo, Outcome 13 Prostatitis symptoms: subgroup analysis (co‐interventions).
Figuras y tablas -
Analysis 3.13

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

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Comparison 3 Antibiotic therapy versus placebo, Outcome 14 Adverse events: subgroup analysis (co‐interventions).
Figuras y tablas -
Analysis 3.14

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

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Comparison 4 Antiinflammatories versus placebo, Outcome 1 Prostatitis symptoms.
Figuras y tablas -
Analysis 4.1

Comparison 4 Antiinflammatories versus placebo, Outcome 1 Prostatitis symptoms.

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Comparison 4 Antiinflammatories versus placebo, Outcome 2 Prostatitis symptoms: pain.
Figuras y tablas -
Analysis 4.2

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

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Comparison 4 Antiinflammatories versus placebo, Outcome 3 Prostatitis symptoms: urinary.
Figuras y tablas -
Analysis 4.3

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

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Comparison 4 Antiinflammatories versus placebo, Outcome 4 Prostatitis symptoms: quality of life.
Figuras y tablas -
Analysis 4.4

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

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Comparison 4 Antiinflammatories versus placebo, Outcome 5 Prostatitis symptoms: responder rate.
Figuras y tablas -
Analysis 4.5

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

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Comparison 4 Antiinflammatories versus placebo, Outcome 6 Prostatitis symptoms: long term.
Figuras y tablas -
Analysis 4.6

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

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Comparison 4 Antiinflammatories versus placebo, Outcome 7 Adverse events.
Figuras y tablas -
Analysis 4.7

Comparison 4 Antiinflammatories versus placebo, Outcome 7 Adverse events.

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Comparison 4 Antiinflammatories versus placebo, Outcome 8 Urinary symptoms.
Figuras y tablas -
Analysis 4.8

Comparison 4 Antiinflammatories versus placebo, Outcome 8 Urinary symptoms.

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Comparison 4 Antiinflammatories versus placebo, Outcome 9 Prostatitis symptoms: subgroup analysis (co‐interventions).
Figuras y tablas -
Analysis 4.9

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

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Comparison 4 Antiinflammatories versus placebo, Outcome 10 Adverse events.
Figuras y tablas -
Analysis 4.10

Comparison 4 Antiinflammatories versus placebo, Outcome 10 Adverse events.

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Comparison 5 Phytotherapy versus placebo, Outcome 1 Prostatitis symptoms.
Figuras y tablas -
Analysis 5.1

Comparison 5 Phytotherapy versus placebo, Outcome 1 Prostatitis symptoms.

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Comparison 5 Phytotherapy versus placebo, Outcome 2 Prostatitis symptoms: pain subscore.
Figuras y tablas -
Analysis 5.2

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

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Comparison 5 Phytotherapy versus placebo, Outcome 3 Prostatitis symptoms: urinary symptoms.
Figuras y tablas -
Analysis 5.3

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

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Comparison 5 Phytotherapy versus placebo, Outcome 4 Prostatitis symptoms: quality of life.
Figuras y tablas -
Analysis 5.4

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

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Comparison 5 Phytotherapy versus placebo, Outcome 5 Prostatitis symptoms: responder rate.
Figuras y tablas -
Analysis 5.5

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

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Comparison 5 Phytotherapy versus placebo, Outcome 6 Adverse events.
Figuras y tablas -
Analysis 5.6

Comparison 5 Phytotherapy versus placebo, Outcome 6 Adverse events.

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Comparison 5 Phytotherapy versus placebo, Outcome 7 Sexual dysfunction.
Figuras y tablas -
Analysis 5.7

Comparison 5 Phytotherapy versus placebo, Outcome 7 Sexual dysfunction.

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Comparison 5 Phytotherapy versus placebo, Outcome 8 Urinary symptoms.
Figuras y tablas -
Analysis 5.8

Comparison 5 Phytotherapy versus placebo, Outcome 8 Urinary symptoms.

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Comparison 5 Phytotherapy versus placebo, Outcome 9 Prostatitis symptoms: subgroup analysis (co‐interventions).
Figuras y tablas -
Analysis 5.9

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

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Comparison 5 Phytotherapy versus placebo, Outcome 10 Adverse events: subgroup analysis (co‐interventions).
Figuras y tablas -
Analysis 5.10

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

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Comparison 6 Botulinum toxin A versus placebo, Outcome 1 Prostatitis symptoms.
Figuras y tablas -
Analysis 6.1

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

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Comparison 6 Botulinum toxin A versus placebo, Outcome 2 Prostatitis symptoms: pain subscore.
Figuras y tablas -
Analysis 6.2

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

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Comparison 6 Botulinum toxin A versus placebo, Outcome 3 Prostatitis symptoms: urinary subscore.
Figuras y tablas -
Analysis 6.3

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

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

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

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

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

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Comparison 6 Botulinum toxin A versus placebo, Outcome 6 Urinary symptoms.
Figuras y tablas -
Analysis 6.6

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

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Comparison 7 Allopurinol versus placebo, Outcome 1 Prostatitis symptoms.
Figuras y tablas -
Analysis 7.1

Comparison 7 Allopurinol versus placebo, Outcome 1 Prostatitis symptoms.

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Comparison 7 Allopurinol versus placebo, Outcome 2 Prostatitis symptoms: pain subscore.
Figuras y tablas -
Analysis 7.2

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

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

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

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Comparison 8 Traditional chinese medicine versus placebo or usual care, Outcome 1 Prostatitis symptoms.
Figuras y tablas -
Analysis 8.1

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

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Comparison 8 Traditional chinese medicine versus placebo or usual care, Outcome 2 Prostatitis symptoms: pain subscore.
Figuras y tablas -
Analysis 8.2

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

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Comparison 8 Traditional chinese medicine versus placebo or usual care, Outcome 3 Prostatitis symptoms: urinary subscore.
Figuras y tablas -
Analysis 8.3

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

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Comparison 8 Traditional chinese medicine versus placebo or usual care, Outcome 4 Prostatitis symptoms: quality of life.
Figuras y tablas -
Analysis 8.4

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

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Comparison 8 Traditional chinese medicine versus placebo or usual care, Outcome 5 Adverse events.
Figuras y tablas -
Analysis 8.5

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

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

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

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Comparison 8 Traditional chinese medicine versus placebo or usual care, Outcome 7 Anxiety and depression: anxiety.
Figuras y tablas -
Analysis 8.7

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

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

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

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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 LOWa,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 LOWa,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 LOWa,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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊕⊝
MODERATEa

‐

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)

⊕⊕⊕⊝
MODERATEa

‐

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)

⊕⊕⊝⊝
LOWa,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

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.

Figuras y tablas -
Summary of findings for the main comparison. Alpha blockers compared to placebo for chronic prostatitis/chronic pelvic pain syndrome
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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)

⊕⊕⊕⊝
MODERATEa

‐

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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊝⊝
LOWa,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

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.

Figuras y tablas -
Summary of findings 2. 5‐alpha reductase inhibitors compared to placebo for chronic prostatitis/chronic pelvic pain syndrome
Ir a la tabla de la revisión
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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊝⊝
LOWb,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)

⊕⊕⊕⊝
MODERATEc,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)

⊕⊕⊕⊝
MODERATEb

‐

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)

⊕⊕⊕⊝
MODERATEc

‐

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

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.

Figuras y tablas -
Summary of findings 3. Antibiotic therapy compared to placebo for chronic prostatitis/chronic pelvic pain syndrome
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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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊝⊝
LOWa,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

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.

Figuras y tablas -
Summary of findings 4. Anti‐inflammatories compared to control for chronic prostatitis/chronic pelvic pain syndrome
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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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊕⊝
MODERATEa

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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊝⊝
LOWa,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

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.

Figuras y tablas -
Summary of findings 5. Phytotherapy compared to placebo or other agents for chronic prostatitis/chronic pelvic pain syndrome
Ir a la tabla de la revisión
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)

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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊝⊝
LOWb,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)

⊕⊕⊝⊝
LOWd,e

RR 5.00
(0.25 to 99.95)

Study population

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

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.

Figuras y tablas -
Summary of findings 6. Botulinum toxin A compared to placebo for chronic prostatitis/chronic pelvic pain syndrome
Ir a la tabla de la revisión
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)

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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊝⊝
LOWb,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

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).

Figuras y tablas -
Summary of findings 7. Allopurinol compared to placebo for chronic prostatitis/chronic pelvic pain syndrome
Ir a la tabla de la revisión
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)

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)

⊕⊕⊝⊝
LOWa,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)

⊕⊕⊝⊝
LOWb,c

RR 1.34
(0.22 to 8.02)

Study population

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)

⊕⊕⊕⊝
MODERATEb

‐

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)

⊕⊕⊝⊝
LOWb,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

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.

Figuras y tablas -
Summary of findings 8. Traditional Chinese Medicine compared to placebo or usual care for chronic prostatitis/chronic pelvic pain syndrome
Ir a la tabla de la revisión
Table 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

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.

Figuras y tablas -
Table 1. Description of the interventions by study
Ir a la tabla de la revisión
Table 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

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.

Figuras y tablas -
Table 2. Description of studies
Ir a la tabla de la revisión
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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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) Show forest plot

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) Show forest plot

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) Show forest plot

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) Show forest plot

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]
Figuras y tablas -
Comparison 1. Alpha‐blockers versus placebo
Ir a la tabla de la revisión
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 Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

2 Prostatitis symptoms: responder rate Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

3 Adverse events Show forest plot

2

105

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.33, 2.30]
Figuras y tablas -
Comparison 2. 5 alpha reductase inhibitors versus placebo
Ir a la tabla de la revisión
Comparison 3. Antibiotic therapy versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Prostatitis symptoms Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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) Show forest plot

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) Show forest plot

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) Show forest plot

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) Show forest plot

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]
Figuras y tablas -
Comparison 3. Antibiotic therapy versus placebo
Ir a la tabla de la revisión
Comparison 4. Antiinflammatories versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Prostatitis symptoms Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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) Show forest plot

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 Show forest plot

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]
Figuras y tablas -
Comparison 4. Antiinflammatories versus placebo
Ir a la tabla de la revisión
Comparison 5. Phytotherapy versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Prostatitis symptoms Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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) Show forest plot

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) Show forest plot

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]
Figuras y tablas -
Comparison 5. Phytotherapy versus placebo
Ir a la tabla de la revisión
Comparison 6. Botulinum toxin A versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Prostatitis symptoms Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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]
Figuras y tablas -
Comparison 6. Botulinum toxin A versus placebo
Ir a la tabla de la revisión
Comparison 7. Allopurinol versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Prostatitis symptoms Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

2 Prostatitis symptoms: pain subscore Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

3 Prostatitis symptoms: urinary subscore Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected
Figuras y tablas -
Comparison 7. Allopurinol versus placebo
Ir a la tabla de la revisión
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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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 Show forest plot

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]
Figuras y tablas -
Comparison 8. Traditional chinese medicine versus placebo or usual care
Ir a la tabla de la revisión