Dr Toni Hazell presents two case studies that explore common causes and primary care management of lower urinary tract symptoms in men

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Dr Toni Hazell

  • common symptoms and causes of lower urinary tract symptoms (LUTS) in men
  • investigations for and management of LUTS in primary care
  • red flags for referral for suspected bladder or prostate cancer.

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Lower urinary tract symptoms (LUTS) are common in primary care, and their prevalence increases with age.1 Most elderly men have LUTS to some degree, but symptoms only cause problems in around 30% of men aged over 65 years.1 Many men with LUTS are concerned about prostate cancer—it is reassuring, therefore, to know that men who report LUTS are not at increased risk of advanced or fatal prostate cancer compared with men without LUTS, and that few will experience complications such as urinary retention or kidney stones.2

Case 1

A 65-year-old man has come to see you ‘about my waterworks, doctor’. He has noticed that, over the last few years, his urinary stream has become gradually weaker, with hesitancy on starting and some terminal dribbling. He is otherwise healthy and takes no regular medications; he had recent blood tests for diabetes, lipids, and renal and liver function, the results of which were normal.

Diagnosis

This man is describing voiding LUTS. In the absence of any known medical history, this is likely to be due to benign prostatic hyperplasia, which is the most common cause of voiding symptoms.3 Other causes of voiding LUTS are listed in Box 1.

Box 1: Causes of voiding LUTS3

  • Benign prostatic hyperplasia or benign prostatic enlargement—the most common cause of voiding symptoms
  • Drugs with an antimuscarinic action (such as tricyclic antidepressants, sedating antihistamines, antimuscarinic drugs for urinary incontinence, and disopyramide)
  • Diabetic autonomic neuropathy and neurogenic bladder
  • Urethral stricture and phimosis (constriction of the foreskin)
  • Cancer of the prostate, bladder, or rectum.

© NICE 2019. LUTS in men: what causes it? Available from: cks.nice.org.uk/topics/luts-in-men/background-information/causes-of-luts All rights reserved. Subject to Notice of rights. NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication. See www.nice.org.uk/re-using-our-content/uk-open-content-licence for further details.

It is important to ask about red-flag symptoms to exclude diagnoses such as urological cancer (see Box 2).4 Specific questions about haematuria, weight loss, and bone pain are useful, and a digital rectal examination should be performed to assess whether:5

  • the prostate is of normal size or enlarged, and whether any enlargement is diffuse, with a palpable median sulcus
  • the prostate is hard or irregular with an impalpable sulcus
  • there are nodules or tenderness.

Asking the patient to fill in an International Prostate Symptom Score (IPSS) questionnaire6 can help to judge the impact of his symptoms on quality of life and guide treatment. NICE recommends carrying out a urine dipstick test and considering blood tests for renal function if there is chronic retention, recurrent urinary tract infection (UTI), or a history of renal stones.7

Box 2: NICE criteria for suspected prostate cancer and bladder cancer4

Prostate cancer

  • Refer men using a suspected cancer pathway referral (for an appointment within 2 weeks) for prostate cancer if their prostate feels malignant on digital rectal examination
  • Consider a prostate-specific antigen (PSA) test and digital rectal examination to assess for prostate cancer in men with:
    • any lower urinary tract symptoms, such as nocturia, urinary frequency, hesitancy, urgency, or retention, or
    • erectile dysfunction, or
    • visible haematuria
  • Refer men using a suspected cancer pathway referral (for an appointment within 2 weeks) for prostate cancer if their PSA levels are above the age-specific reference range.

Bladder cancer

  • Refer people using a suspected cancer pathway referral (for an appointment within 2 weeks) for bladder cancer if they are:
    • aged ≥45 and have:
      • unexplained visible haematuria without urinary tract infection, or
      • visible haematuria that persists or recurs after successful treatment of urinary tract infection, or
    • aged ≥60 and have unexplained non-visible haematuria and either dysuria or a raised white cell count on a blood test
  • Consider non-urgent referral for bladder cancer in people aged ≥60 with recurrent or persistent unexplained urinary tract infection.

© NICE 2015. Suspected cancer: recognition and referral. Available from: www.nice.org.uk/guidance/ng12 All rights reserved. Subject to Notice of rights. NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication. See www.nice.org.uk/re-using-our-content/uk-open-content-licence for further details.

A prostate-specific antigen (PSA) test is indicated if symptoms are suggestive of benign prostatic enlargement, if requested by a concerned patient, or if the prostate feels abnormal,7 but it is important that the patient understands that the PSA test does not have high specificity or sensitivity for prostate cancer (see Box 3).7,8 NICE recommends that this is discussed with the patient before testing;7 in addition, you may find it helpful to signpost online information on the subject.8,9

Box 3: Reasons why interpreting PSA results can be difficult7

  • An increased serum PSA level can be present with:
    • prostate enlargement
    • older age (PSA levels normally increase with age)
    • infection (for example, prostatitis and urinary tract infection)
    • physical causes, including following vigorous exercise, digital rectal examination, catheterisation, and prostate biopsy
    • prostate cancer
    • a normal prostate
  • A normal serum PSA level can be present with:
    • prostate enlargement
    • prostate cancer
    • infection
  • A decreased serum PSA level can be present with:
    • the use of certain drugs, including 5-alpha reductase inhibitors (a decrease in PSA levels is seen rapidly, within the first few months of treatment), aspirin, statins, and thiazide diuretics
    • obesity
  • For detailed information on PSA testing, see the section on Information about PSA testing in the NICE CKS topic on Prostate cancer.

PSA=prostate-specific antigen; CKS=clinical knowledge summary

© NICE 2019. LUTS in men: what investigations should I arrange for a man presenting with lower urinary tract symptoms? Available from: cks.nice.org.uk/topics/luts-in-men/diagnosis/investigations All rights reserved. Subject to Notice of rights. NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication. See www.nice.org.uk/re-using-our-content/uk-open-content-licence for further details.

Management

Management depends on clinical findings and the result of the PSA test, if done.10

Mild symptoms (IPSS ≤7) can be managed conservatively, with bladder and pelvic floor muscle training and advice on fluid intake and other lifestyle measures, such as avoiding constipation, maintaining a healthy weight, and limiting intake of caffeine, artificial sweeteners, and fizzy drinks.10

Moderate-to-severe symptoms (IPSS ≥8) are treated with an alpha blocker, such as alfuzosin, doxazosin, tamsulosin, or terazosin—review for symptoms and quality of life at 4–6 weeks and then every 6–12 months.10

If there is an enlarged prostate and a risk of progression, consider a 5-alpha reductase inhibitor, such as finasteride or dutasteride—risk of progression increases with higher PSA levels, a larger prostate, higher symptom scores, and any evidence of bladder decompensation, such as chronic retention. Both drugs can be combined in patients with severe symptoms and an enlarged prostate.10

Finally, referral to a urologist may be considered if medical management doesn’t improve symptoms and there is a possible need for surgery, such as a transurethral resection of the prostate.10

Clinical outcome

This patient has an IPSS of 10 and is quite bothered by his symptoms, but his prostate seems to be of normal size. You therefore start him on an alpha blocker—this controls his symptoms well and he remains on it long term.

Case 2

An 80-year-old man has come to see you to discuss his urinary problems. For the last few days, he is having to pass urine increasingly frequently, sometimes every hour, and he is getting up a few times in the night. Sometimes, when he has just urinated, he has to go again within 10 minutes or so, and he is finding this very difficult. He has once or twice been incontinent at night, but never during the day. His urine stream is normal, and he has no haematuria, dysuria, or other symptoms. His medical history shows that he has type 2 diabetes that is not particularly well controlled. In addition, his family have raised concerns about poor memory, and he is awaiting a memory clinic appointment.

Diagnosis

These are storage symptoms, which represent overactive bladder syndrome, defined by NICE as ‘the set of symptoms that include urgency, with or without urgency incontinence, and the sensation of needing to pass urine again just after urinating’.3 He does not appear to have any voiding symptoms, nor are there any red flags for prostate cancer.

It is often not possible to identify a cause for overactive bladder syndrome and we sometimes end up just treating the symptoms, but it is important to think about the underlying causes so that they can be confirmed or excluded before treatment. Causes of overactive bladder syndrome are listed in Box 4.

Box 4: Causes of overactive bladder syndrome3

  • Benign prostatic hyperplasia and benign prostatic enlargement
  • Neurological conditions (such as dementia, diabetic neuropathy, multiple sclerosis, Parkinson’s disease, and stroke)
  • Lower urinary tract infection, sexually transmitted infections, and prostatitis
  • Bladder stones
  • Cancer of the bladder and prostate. 

© NICE 2019. LUTS in men: what causes it? Available from: cks.nice.org.uk/topics/luts-in-men/background-information/causes-of-luts All rights reserved. Subject to Notice of rights. NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication. See www.nice.org.uk/re-using-our-content/uk-open-content-licence for further details.

The diagnosis will be made partly by performing a thorough examination with the causes of overactive bladder in mind (see Box 4), and partly through knowledge of the patient’s medical history. As with all LUTS, the urine should be dipstick tested.7 Bedwetting is a sign of chronic urinary retention, so it may also be appropriate to check renal function.7 This man’s symptoms are not immediately suggestive of prostatic enlargement, so a PSA test may not be needed.

A urinary frequency and volume chart can be downloaded11 and the man should be asked to fill it in. The pattern of passing urine can give a clue as to the cause of overactive bladder—if the frequency is high, but the 24-hour volume of urine is normal (up to 3 litres/day), then bladder capacity may be too low (a male bladder can usually hold 300–600 ml of urine without the need to urinate).5 The volume of urine passed at night should be no more than 35% of the 24-hour urine production.5 If it is more than this, then options include advising the patient to limit afternoon/evening fluid intake, administering an afternoon diuretic, or—after seeking advice from a specialist—prescribing a low dose of desmopressin.12 Polyuria can be caused by conditions such as undiagnosed or undertreated diabetes, and this should be considered.3 It is also worth asking the patient to fill in an IPSS questionnaire.6

Management

If a treatable cause is identified, then this should be addressed. If no cause is found for the symptoms, then the management is that of idiopathic overactive bladder syndrome. Lifestyle issues should be resolved first. A balance needs to be struck on fluid intake, which should be neither excessive nor restricted so much that there is a risk of UTI. If the patient has a raised body mass index, then weight loss is a good idea, as is managing any constipation and advising the patient to limit their intake of fizzy drinks, artificial sweeteners, alcohol, and caffeine.13 It is also sensible to advise smoking cessation if relevant.

Bladder training or bladder drill is another conservative measure that can be tried—depending on pathways in your area, you may be able to refer the patient for bladder training supervised by a continence nurse or physiotherapist, or the patient may have to do it on his own, with assistance from printable resources.14 If there is a current continence issue, then pads or sheaths may provide a temporary solution,13 but they should not be used in place of medical management unless there are reasons why management options are limited (for example, in palliative care).

Treatment for idiopathic overactive bladder syndrome is with an antimuscarinic drug, such as oxybutynin, tolterodine, or darifenacin.13 However, immediate-release oxybutynin can impair daily functioning and memory in older men, and would therefore not be appropriate in this case.13 A first-line drug should be tried for at least 4–6 weeks; subsequently, an alternative should be offered if the first-line drug is ineffective or poorly tolerated.13 Antimuscarinic drugs have significant side-effects, including dry mouth, constipation, drowsiness, and blurred vision, and it is common for patients to stop taking them (with or without telling their doctor),15 so ask about adherence in a non-judgemental way. In recent years, concerns have also been raised about the long-term use of antimuscarinic drugs and cognitive performance16 and dementia.17 This has led some CCGs to issue guidance ensuring that doctors are aware of the anti-cholinergic burden of drugs and the cumulative effects of multiple antimuscarinic drugs.18,19 Antimuscarinic drugs are not used solely for urinary symptoms, so it is possible that a patient may be on a variety of anti-cholinergic drugs at the same time; for example, an antimuscarinic for overactive bladder, an antihistamine, a tricyclic antidepressant, and an analgesic, such as tramadol.

If an antimuscarinic does not control symptoms, or is felt to be contraindicated, then the next-line drug is mirabegron, a beta-3-adrenergic receptor agonist that relaxes the bladder muscles.13,20 It is more expensive than many antimuscarinic drugs and is only approved for use by NICE when antimuscarinic drugs are contraindicated, clinically ineffective, or have unacceptable side-effects.20 Contraindications include severe hypertension (≥180 mmHg systolic or 110 mmHg diastolic); the dose of mirabegron should be reduced if there is hepatic impairment or renal impairment, and the drug is contraindicated if hepatic or renal impairment is severe (see Box 5).21

Box 5: Prescribing information for mirabegron21

What are the contraindications and cautions for mirabegron?

  • Do not prescribe mirabegron to people with:
    • severe uncontrolled hypertension (systolic blood pressure of ≥180 mmHg and/or diastolic blood pressure of ≥110 mmHg)—measure blood pressure before starting treatment with mirabegron and monitor regularly during treatment, especially in people with hypertension
    • severe hepatic impairment
    • moderate hepatic impairment who are also taking strong cytochrome P450 inhibitors, such as itraconazole, ritonavir, and clarithromycin
    • end-stage renal disease (estimated glomerular filtration rate [eGFR] <15 ml/minute/1.73 m2)
    • severe renal impairment (eGFR 15–29 ml/minute/1.73 m2) who are also taking strong cytochrome P450 inhibitors, such as itraconazole, ritonavir, and clarithromycin
  • Use mirabegron with caution in people with:
    • bladder outlet obstruction
  • Reduce the starting dose of mirabegron to 25 mg once daily in people with:
    • moderate hepatic impairment
    • mild hepatic impairment who are also taking a strong cytochrome P450 inhibitor, such as clarithromycin, itraconazole, and ritonavir
    • severe renal impairment (eGFR 15–29 ml/minute/1.73 m2)
    • mild-to-moderate renal impairment (eGFR 30–89 ml/minute/1.73 m2) who are also taking a strong cytochrome P450 inhibitor, such as clarithromycin, itraconazole, and ritonavir.

How should I start and titrate mirabegron?

  • The recommended starting dose of mirabegron is 50 mg once daily
  • A recommended starting dose of 25 mg daily is recommended for people with:
    • moderate hepatic impairment
    • mild hepatic impairment who are also taking a strong cytochrome P450 inhibitor, such as clarithromycin, itraconazole, and ritonavir
    • severe renal impairment (eGFR 15–29 ml/minute/1.73 m2)
    • mild-to-moderate renal impairment (eGFR 30–89 ml/minute/1.73 m2) who are also taking a strong cytochrome P450 inhibitor, such as clarithromycin, itraconazole, and ritonavir.

What are the adverse effects of mirabegron?

  • Adverse effects of mirabegron include:
    • common and very common—arrhythmias, constipation, diarrhoea, dizziness, headache, increased risk of infection (for example, urinary tract infections), and nausea
    • uncommon—cystitis, dyspepsia, gastritis, joint swelling, palpitations, and skin reactions
    • rare or very rare—angioedema, eyelid oedema, hypersensitivity vasculitis, hypertensive crisis, lip swelling, and urinary retention
    • frequency not known—insomnia.

What are the key drug interactions of mirabegron?

  • Drug interactions of mirabegron include:
    • strong cytochrome P450 inhibitors —plasma concentrations of mirabegron may be increased by concurrent use with strong cytochrome P450 inhibitors
      • avoid or reduce the starting dose of mirabegron in people with hepatic or renal impairment who are also taking a strong cytochrome P450 inhibitor, such as clarithromycin, itraconazole, and ritonavir
    • dabigatran —be aware that mirabegron is predicted to increase the exposure to dabigatran
    • digoxin —concurrent use with mirabegron increases the plasma concentration of digoxin
      • reduce initial dose of digoxin
    • metoprolol —mirabegron increases the plasma concentration of metoprolol
      • if concomitant use is necessary, consider reducing the dose of metoprolol.

For a complete list of possible drug interactions of mirabegron, see the electronic Medicines Compendium (www.medicines.org.uk) or the British National Formulary (bnf.nice.org.uk).

© NICE 2019. LUTS in men: mirabegron Available from: cks.nice.org.uk/topics/luts-in-men/prescribing-information/mirabegron All rights reserved. Subject to Notice of rights. NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication. See www.nice.org.uk/re-using-our-content/uk-open-content-licence for further details.

If all of these primary care options fail, then referral is indicated—in secondary care, options include botulinum injection into the bladder wall, cystoplasty, and implanted sacral nerve stimulation.13 A useful thing to suggest while symptoms are ongoing is that the patient orders a ‘Just can’t wait’ card if he regularly needs to use a toilet while out and about—many shops will allow access to customer toilets if shown this.22

Clinical outcome

At first, you think that a UTI is unlikely because there is no dysuria; however, given the sudden onset of symptoms, you look carefully at the urine dipstick, which is positive for white cells and nitrites. Infection is confirmed on culture and the symptoms resolve on treatment. You make a mental note to be more aware of the possibility of UTI in elderly men without dysuria—NICE advises that, in men aged 65 years or older, UTI is likely with dysuria alone, or two or more of the following symptoms:23

  • temperature 1.5ºC above normal twice in 12 hours
  • frequency or urgency
  • incontinence
  • worsening delirium or debility
  • suprapubic pain
  • visible haematuria.

Summary

LUTS are common in men, with prostatic enlargement and overactive bladder being the more common causes,24 but it is important to be aware of the possibility of acute diagnoses such as UTI, possible signs of malignancy, and interactions with other medical conditions and drugs. Diagnostic tools, such as the IPSS and a urinary frequency and volume chart, may be useful in elucidating the cause of LUTS in men.

Dr Toni Hazell

Part-time GP, Greater London

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References

  1. NICE. LUTS in men: how common is it? NICE Clinical Knowledge Summary. cks.nice.org.uk/topics/luts-in-men/background-information/prevalence/ (accessed 4 March 2021).
  2. NICE. LUTS in men: what is the prognosis? NICE Clinical Knowledge Summary. cks.nice.org.uk/topics/luts-in-men/background-information/prognosis/ (accessed 4 March 2021).
  3. NICE. LUTS in men: what causes it? NICE Clinical Knowledge Summary. cks.nice.org.uk/topics/luts-in-men/background-information/causes-of-luts (accessed 4 March 2021).
  4. NICE. Suspected cancer: recognition and referral. NICE Guideline 12. NICE, 2015. Available at: www.nice.org.uk/guidance/ng12
  5. NICE. LUTS in men: how should I assess a man with lower urinary tract symptoms? NICE Clinical Knowledge Summary. cks.nice.org.uk/topics/luts-in-men/diagnosis/assessment (accessed 4 March 2021).
  6. Royal United Hospitals Bath NHS Foundation Trust. International prostate symptom score (IPSS). Bath: Royal United Hospitals Bath NHS Foundation Trust, 2017. Available at: www.ruh.nhs.uk/patients/urology/documents/patient_leaflets/form_ipss.pdf
  7. NICE. LUTS in men: what investigations should I arrange for a man presenting with lower urinary tract symptoms? NICE Clinical Knowledge Summary. cks.nice.org.uk/topics/luts-in-men/diagnosis/investigations (accessed 4 March 2021).
  8. Prostate Cancer UK website. The PSA test. prostatecanceruk.org/prostate-information/prostate-tests/psa-test#advantages-disadvantages (accessed 4 March 2021).
  9. Public Health England, Cancer Research UK, Prostate Cancer UK. PSA testing and prostate cancer: advice for well men aged 50 and over. London: PHE, 2020. Available at: assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/856976/PSA_testing_for_prostate_cancer_information_for_well_men.pdf
  10. NICE. LUTS in men: scenario: voiding symptoms. NICE Clinical Knowledge Summary. cks.nice.org.uk/topics/luts-in-men/management/voiding-symptoms (accessed 4 March 2021).
  11. Bladder Matters. Frequency and volume chart. Bladder Matters. Available at: bladdermatters.co.uk/downloads/85923fchart.pdf
  12. NICE. LUTS in men: scenario: nocturnal polyuria. NICE Clinical Knowledge Summary. cks.nice.org.uk/topics/luts-in-men/management/nocturnal-polyuria (accessed 4 March 2021).
  13. NICE. LUTS in men: scenario: overactive bladder. NICE Clinical Knowledge Summary. cks.nice.org.uk/topics/luts-in-men/management/overactive-bladder (accessed 4 March 2021).
  14. Sandwell Community Continence Service. Bladder retraining: information and advice for patients. Sandwell, Sandwell and West Birmingham Hospitals NHS Trust, 2012. Available at: swbh.nhs.uk/wp-content/uploads/2012/06/Bladder-retraining-ML3615.pdf
  15. Robinson D, Cardozo L. Antimuscarinic drugs to treat overactive bladder. BMJ 2012; 344: e2130.
  16. Ziad A, Olekhnovitch R, Ruiz F et al. Anticholinergic drug use and cognitive performances in middle age: findings from the CONSTANCES cohort. Neurol Neurosurg Psychiatry 2018; 89 (10): 1107–1115.
  17. Coupland C, Hill T, Dening T et al. Anticholinergic drug exposure and the risk of dementia—a nested case-control study. JAMA Intern Med 2019; 179 (8): 1084–1093.
  18. PrescQIPP website. Anticholinergic drugs. www.derbyshiremedicinesmanagement.nhs.uk/assets/Clinical_Guidelines/Formulary_by_BNF_chapter_prescribing_guidelines/BNF_chapter_4/Anticholinergics_drugs.pdf (accessed 12 March 2021).
  19. West Essex Clinical Commissioning Group. Anticholinergic side-effects and prescribing guidance. Essex: West Essex Clinical Commissioning Group, 2020. Available at: westessexccg.nhs.uk/your-health/medicines-optimisation-and-pharmacy/clinical-guidelines-and-prescribing-formularies/04-central-nervous-system/61-anticholinergic-side-effects-and-prescribing-guidance/file
  20. NICE. Mirabegron for treating symptoms of overactive bladder. Technology Appraisal 290. NICE, 2013. Available at: www.nice.org.uk/ta290
  21. NICE. LUTS in men: mirabegron. NICE Clinical Knowledge Summary. cks.nice.org.uk/topics/luts-in-men/prescribing-information/mirabegron (accessed 4 March 2021).
  22. Bladder & Bowel UK website. BBUK’s Just Can’t Wait cards. www.bbuk.org.uk/just-cant-wait-cards (accessed 4 March 2021).
  23. NICE. Urinary tract infection (lower)—men: when should I suspect a urinary tract infection in a man? NICE Clinical Knowledge Summary. cks.nice.org.uk/topics/urinary-tract-infection-lower-men/diagnosis/suspecting-a-urinary-tract-infection (accessed 4 March 2021).
  24. Tidy C, Knott L. Lower urinary tract symptoms in men. patient.info/mens-health/prostate-and-urethra-problems/lower-urinary-tract-symptoms-in-men (accessed 4 March 2021).