Background

Chronic pelvic pain syndrome (CPPS) in men is an important and common condition in genitourinary medicine (GUM) and other sexual health services. It has a lifetime prevalence of 2%–14%.1–4 The terms CPPS and chronic prostatitis are often used interchangeably to describe a syndrome which causes perineal and genital pain that can be unrelenting and physically, as well as emotionally, exhausting.1–5 The median age of patients affected is 43 years and the syndrome is usually of sudden onset,2 ,4 though classically CPPS is only diagnosed when symptoms have been present for at least 3 months.1 ,5 Due to the nature of CPPS pain, including dysuria, penile tip, perineal, testicular and ejaculatory pain, as well as other commonly associated symptoms such as urinary frequency, patients often present to GUM departments, usually at onset of the acute phase; however no data are available as to the frequency of presentation.1 ,5

Managing men with CPPS is challenging as the aetiology is poorly understood, diagnosis is one of exclusion and management strategies are suboptimal.1 ,4 ,5 A number of hypotheses have been proposed as to the causes of CPPS, both infective and non-infective. It is well recognised that men with acute non-gonococcal urethritis (NGU) may go on to develop chronic urethritis.6 Although published data are limited, men with CPPS may have urethritis, and indeed symptom profiles overlap.1 ,6 ,7 ^{W1 W2} Both Mycoplasma genitalium and Ureaplasma urealyticum are associated with chronic NGU although in the majority no infection is detected.6 ^W3 Chronic bacterial prostatitis is identified in up to 10% and is associated with recurrent urinary tract infections.4 ,5 Evidence supports a non-infective aetiology in the majority of cases. An infectious or inflammatory initiator may result in neurological dysfunction leading to increased pelvic tone.1–5 ^W4 There is some evidence to indicate that increased pelvic floor muscle tone may contribute by increasing intraurethral resistance to urinary flow.5 ^W4 This, in turn, may lead to reflux into the prostate causing symptoms.5 ^{W4 W5} There is further evidence that symptoms may be caused by chronically tense myofascial tissue around the pelvic floor.2 ,4 ,5 ,8 ^W5–W7 Underlying anxiety or depression about the cause of symptoms may exacerbate this phenomenon; however, it remains uncertain whether these are premorbid conditions or a result of developing symptoms.1–3 ,5Although this has not been formally assessed, it is our experience in Bristol that men with obsessive personality traits who tend to get locked into circular trains of thought are over-represented in patients with CPPS.

There is no reliable single therapy for effectively treating men with CPPS.1–5Although evidence for antibiotic therapy was thought to be unconvincing, a recent systematic review and meta-analysis suggests that antimicrobials may indeed be effective.9 The exact mechanism of action is unclear as antimicrobials may have other properties such as an anti-inflammatory action.5 ^{W8 W9} Thus, this should not be used to support an infection with an unknown microorganism as a possible cause. The findings also indicate that α-blockers, such as tamsulosin or alfuzosin, are effective with the greatest improvement being observed when a combination of an α-blocker and antibiotic are used.9 Evidence suggests prolonged treatment for more than 6 weeks (likely more than 12 weeks) with an α-blocker is required before a beneficial effect may be observed.4 ,10

There are a number of other therapeutic interventions which have various levels of evidence supporting their use such as non-steroidal anti-inflammatory drugs, finasteride, phytotherapy, myofascial trigger point release and paradoxical relaxation training, acupuncture and exercise.1 ,5 ,8 ,10 ^{W7 W10 W11} Low dose tricyclic antidepressants have been demonstrated to be useful in neuropathic pain although there is no evidence from a randomised controlled trial demonstrating efficacy in men with CPPS.4 ,10 Nickel et al10 have proposed that the traditional pharmacotherapeutic approach to managing patients would be enhanced by addition of a biopsychosocial approach tailored to an individual's presenting symptoms. Westesson and Shoskes demonstrated that multimodal therapy based on clinical presentation (UPOINT phenotype) resulted in significant benefit.8 ^W12

Patient outcome can be quantified using the American National Institutes of Health Chronic Prostatitis Symptom Index score (NIH CPSI).5 ^W13 Scores can range from 0 to 43, with scores closer to 0 reflecting a more favourable status.

We detail below how to set up and run a clinic for men with CPPS using the novel biopsychosocial approach which we have developed, evaluated and demonstrated to be effective resulting in a significant decrease in mean NIH CPSI from 22.6 to 14.4 (p=<0.01).7 In addition, we have identified M. genitalium in only one of nine male patients with chronic NGU in whom this was tested for in the past 3 years. This was probably as a result of re-infection as symptoms resolved on a prolonged course of clarithromycin and he did not receive treatment with moxifloxacin.^W14

Referral criteria and prereferral management

Men with persistent symptoms, despite appropriate investigation and treatment based on the national guideline on the management of NGU,1 ,6 ^W2 in whom a urinary tract infection has been excluded should be referred to the CPPS clinic (see online supplementary appendix 1, figure 1). The role of anxiety and pelvic floor muscle tone should be discussed prior to referral (see online supplementary appendix 1, figure 2). This figure was developed and introduced in 2012. In the online supplementary appendix 1, readers will find these aforementioned figures and indepth detail of the management strategy of CPPS with additional references.

We have updated our inhouse NGU management guideline in view of the fact that azithromycin 1 g may induce macrolide resistance in M. genitalium.^W14 Doxycycline 100 mg twice daily for 7 days is first line therapy for acute NGU and azithromycin 1 g then 500 mg once daily for 4 days plus metronidazole 400 mg for 5 days is first line therapy for chronic NGU (see online supplementary appendix 1, figure 1). Evidence would also support azithromycin 500 mg then 250 mg once daily for 4 days.^W14

Managing patients with chronic pelvic pain

Management

The primary aim is to exclude all potential and treatable causes and in so doing address the patients’ underlying anxieties which often centre on unknown (potentially transmissible) infection or cancer. The goal is not curing the patients but improving their symptoms so that they become manageable—it is important to be realistic. In our experience, patients understand that most people have some intermittent aches or pains.

The role of the urethral smear for detecting urethritis, when taken correctly, is its high negative predictive value for an STI, notably M. genitalium for which there is currently only limited access to specific diagnostic testing. With each course of antibiotics targeted at different pathogens, its positive predictive value for detecting an STI decreases. There should be a discussion about how anxiety can lead to increased pelvic tone which could result in back flow/pressure of urine into the prostate resulting in referred pelvic pain. This should be undertaken while referring to online supplementary appendix 1, figure 2 and a diagram of the male pelvic floor structures (eg, http://www.patient.co.uk/health/chronic-prostatitis patient leaflet). It should be explained that often the precipitating factor has either resolved or, as indicated by the history, specific investigations are being carried out and/or treatment is being initiated, in order to ensure that this is the case.

A leaflet on pelvic floor relaxation upon voiding should be provided and discussed (http://www.ocurology.com/Pelvic_Floor_Dysfunction_handout.pdf) and advice given about distraction techniques when the pain is present. Mindfulness and yoga may also have a role here. In our experience, exercise can be an effective distraction technique and may have other beneficial properties.^{W17 W18} Accurate and concise written information in the form of a patient leaflet with online resources and references should also be provided (Bristol CPPS leaflet available on request).

In our experience, men can be divided into four broad categories based on the initial clinical findings.

• Category 1: At risk of an STI urethral smear positive

• Category 2: At risk of an STI urethral smear negative

• Category 3: Low risk of an STI urethral smear positive

• Category 4: Low risk of an STI urethral smear negative

(Please see figure 1 for management pathway and online supplementary appendix 1 for a detailed discussion of how to apply this and manage sexual partner(s)). Usually patients improve gradually and value the support and reassurance provided at each visit.7 This protocol was developed by a single physician (PH) without recourse to a multidisciplinary team. It is likely that a multidisciplinary team approach, incorporating psychology, physiotherapy, GUM, urology and a chronic pain specialist, would further improve outcomes.7 ,8 ,10

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Figure 1

Flow diagram of the structured management approach to men attending a CPPS clinic.