Section 1: Epidemiology and aetiology
In order to explore the epidemiology of benign prostatic hyperplasia (BPH), one must first consider its definition.
BPH is in fact only a histological diagnosis and bears no relationship to symptoms. In order to prove that a patient has BPH, one requires a biopsy showing hyperplasia of prostatic stromal cells. BPH commonly affects the transitional zone of the prostate, which encircles the urethra and thus leads to restriction of flow out of the bladder. This is termed benign prostatic obstruction (BPO). The correct term for the diagnosis of an enlarged prostate, felt on digital rectal examination (DRE) is benign prostatic enlargement (BPE).
BPH is the most common benign neoplasm in males. Autopsy studies estimate that 40% of men in their 50s, 70% in their 60s and 88% in their 80s will have evidence of BPH.1 However, not all these men will have had BPO during life. A large European analysis of family physician records found an overall prevalence of lower urinary tract symptoms (LUTS) suggestive of the incidence of BPH being 10.3% in men older than 45, which increased to 24% at age 80.2
Hyperplasia in the prostate is stimulated by androgens. The most potent androgen is dihydrotestosterone, which is converted from testosterone by the enzyme 5-alpha reductase. The hyperplasia includes both smooth muscle cells and glandular connective tissue. In addition, smooth muscle in the prostate may be further contracted by the sympathetic nervous system perpetuating any existing obstruction, known as the dynamic mechanism of obstruction. The increase in the bulk of the prostate causes obstruction by the static mechanism.
The aetiology is multifactorial with advancing age, endogenous androgens and prostate volume increasing the risk of developing symptoms. Black men appear to have a higher risk and Asian men have a lower risk.
However, the risk for Asian men living in western society approximates that of the host society. This points towards unclear environmental causality.3
Section 2: Making the diagnosis
BPH should be suspected in middle-aged and elderly men with LUTS. Classically, a man over the age of 50 will report a weak stream with difficulty starting and stopping his flow.
A small proportion of men present with urine retention, which is a complication of untreated BPH. Acute retention is the inability to pass urine and is associated with suprapubic pain and a palpable bladder. This is a urological emergency and the bladder requires immediate drainage. Men presenting under the age of 50 with voiding LUTS are unlikely to have BPH. Patients with previous pelvic surgery or neurological disorders should be referred for specialist input because they may have detrusor underactivity or sphincteric dyssynergia.
Having made a diagnosis of BPO, the international prostate symptom score (IPSS) may be used to quantify severity. It has been shown that 20% of GPs use scoring questionnaires.4 This is primarily useful in choosing appropriate treatments and predicting and assessing response to treatment, which should commence in primary care.
Examination for BPH begins with abdominal, digital rectal and a focused neurological examination. Abdominal examination should assess for a palpable bladder and other abdominal masses. The DRE should assess perianal sensation, anal tone, prostate size and for any prostatic irregularity. This is the only sound method of diagnosing a prostate cancer. If a prostatic nodule is palpable then a PSA test should be considered along with appropriate referral to a urologist.
All patients should have a urine dipstick and/or culture and sensitivity to rule out a UTI or haematuria. NICE guidelines recommend that all patients with LUTS suggestive of renal impairment should have a serum creatinine and eGFR, which may be associated with chronic retention. Renal impairment should be suspected if there is a palpable bladder, nocturnal enuresis, recurrent UTI and history of stone disease. If renal impairment is present, an ultrasound scan should be requested to assess for hydronephrosis and post-void residual.
Investigations may include a urinary flow rate and post-void residual estimation. The maximum flow rate (Qmax) and pattern of flow are important to the urologist. There is less than a 30% likelihood of bladder outlet obstruction due to BPH if the Qmax is greater than 15ml/s, but more than a 90% likelihood if it is less than 12ml/s. Post-void residuals greater than 200ml may indicate a less favourable response to treatment and a GP should refer patients with consistently high residuals to a urologist. A flow meter and bladder scanner, however, may not be accessible to all GPs and therefore this needs to be accounted for by commissioning services.
PSA has a useful role in the assessment of LUTS by acting as a surrogate marker in benign disease for an enlarged prostate. The weight of evidence suggests that men with a PSA >1.4ng/ml should be considered to be at increased risk of disease progression of BPH.5,6 A note of caution should remain that a PSA test cannot replace a DRE and should not be done in its absence. Another concern among urologists is that the indiscriminate use of the PSA test will result in unnecessary invasive biopsies and overdiagnosis of carcinoma; it has been suggested that up to 50% of patients identified on PSA screening do not have a clinically significant carcinoma.7
The presence of BPH symptoms does not predispose to prostate carcinoma and therefore it is not essential in men with BPH unless an abnormal prostate is felt on DRE or the patient is specifically concerned about or has a family history of prostate carcinoma.8 The NICE guidelines also recommend that a PSA test is offered only after full counselling. One must also exclude a UTI prior to a PSA test and not perform the test within a month of a proven UTI.
|LOWER URINARY TRACT SYMPTOMS|
|STORAGE SYMPTOMS||VOIDING SYMPTOMS||POST-VOID SYMPTOMS|
|Frequency||Slow/splitting/intermittent stream||Feeling of incomplete emptying|
Section 3: Managing the condition
The aim of treating LUTS suggestive of BPH should be to relieve symptoms and improve quality of life, as well as to attempt to prevent progression of disease and the development of complications.
These aims need to be balanced against the potential side-effects of treatment. Therefore watchful waiting is an option recommended for many men. These men should be reassured and educated on the benign nature of the condition.
When conservative options fail, medical therapy may be instituted in primary care. Options for voiding symptoms include alpha-antagonists, 5-alpha reductase inhibitors and combination therapy.
Urogram showing bladder (light) with enlargedprostate beneath (Photograph: Zephyr/SPL)
Inhibition of the noradrenergic alpha-1 receptors relaxes sphincter tone and decreases urinary outflow resistance. Alpha-antagonists act rapidly (usually within 48 hours) and provide a symptomatic improvement that is immediately noticeable to the patient.9
An improvement in symptom scores of 30-40% is reported on average for all the alpha-antagonists, in addition to an improvement in Qmax of 15-30%.10,11
Several studies have shown these agents alleviate symptoms quicker and more effectively than 5-alpha reductase inhibitors.12
Side-effects are due to blockade of alpha-receptors in other organ systems and include postural hypotension, dizziness, headache and failure of ejaculation.
Five-alpha reductase inhibitors
Testosterone is converted to dihydrotestosterone by the enzyme 5-alpha reductase within the prostate cell. Five-alpha reductase inhibitors therefore decrease prostate volume and reduce symptoms by arresting growth and causing prostatic atrophy. Men with larger prostates, higher IPSS scores, PSA>1.4ng/ml and Qmax<12ml/s are most likely to progress symptomatically and have been shown to benefit most from 5-alpha reductase inhibitors.
Two 5-alpha reductase inhibitors are licensed in the UK: finasteride and dutasteride. Five-alpha reductase inhibitors have been shown to decrease symptom scores, decrease prostate volume by 20-30%, increase flow rate and reduce the risk of surgery and acute retention.13,14
It must be remembered that prostate shrinkage takes approximately six months to have an effect on symptoms and flow rate. Side-effects include erectile dysfunction, reduced libido, ejaculatory dysfunction, gynaecomastia, musculoskeletal pain, lethargy and breast tenderness. Caution should be applied in men taking 5-alpha reductase inhibitor therapy because PSA levels will be halved.
This needs to be taken into account if a patient is being followed up or is suspected of having prostate cancer. Therefore if a man is taking a 5-alpha reductase inhibitor, any increases in PSA after six months of therapy are actually twice as high compared to men naive of this therapy and should therefore instigate a urological referral if two increases are witnessed.
There have been two large studies that have shown that combination of an alpha-blocker and 5-alpha reductase inhibitor leads to greater symptomatic relief and reduced progression of disease in men with BPH.15,16
Combination therapy was significantly superior to alpha-blocker monotherapy but not 5-alpha reductase inhibitor monotherapy at reducing the relative risk of acute retention or BPH-related surgery.17
Another combination therapy which is increasingly being used by urologists and should also increase in primary care is that of an alpha-antagonist and anticholinergic. This combination can be used in men with mixed voiding and storage symptoms where the storage symptoms persist after alpha-antagonist therapy.
There was a concern that the use of anticholinergics in men with voiding symptoms may lead to the precipitation of acute urinary retention.
This has not been found to be the case. The NICE guidelines, however, do recommend caution with using anticholinergics in men with a post-void residual volume >150ml and therefore a bladder scanner needs to be available to the primary care physician.
Surgery is performed less commonly now that effective pharmacotherapy is available for BPH, but surgery is an excellent option for improving symptoms and decreasing progression of disease for patients who develop complications or who have inadequately controlled symptoms on medical therapy.18
Section 4: Prognosis
Out of 276 men with BPH symptoms who were assigned to watchful waiting and who received no treatment, 24% progressed to require surgery within three years.18
In men treated with a 5-alpha reductase inhibitor, there is a 5% risk of requiring surgery by four years and a 3% risk of developing acute urinary retention over that time.13
Alpha-antagonists do not delay progression of disease.
The greatest benefit of 5-alpha reductase inhibitor therapy is for prostates larger than 30ml.
Other complications of untreated BPH may include chronic retention, renal impairment, recurrent UTI, bladder stones, haematuria and bladder overactivity.
Follow-up of men for whom watchful waiting is appropriate should include symptom score, abdominal examination and digital rectal assessment with or without PSA.
Deterioration in symptoms should lead to assessment of flow rate and post-void residual.
If treatment has been commenced, then a similar protocol should be followed, bearing in mind that the 5-alpha reductase inhibitor will shrink the prostate and halve the PSA.
The factors that should stimulate the request of a renal function test include a palpable bladder, nocturnal enuresis, recurrent UTIs and history of stone disease.
If new renal impairment is noted, an ultrasound of the kidneys is indicated.
Section 5: Case study
He had visited the practice two weeks previously with symptoms of poor flow, hesitancy and terminal dribbling. He had a non-palpable bladder and benign-feeling prostate. Previously, he had been asked to complete an IPSS form and his PSA had been checked. His IPSS score was 8 and his PSA was 1.2.
In a patient at high risk of cardiovascular side-effects it is not recommended to commence alpha-blockers for mild BPH symptoms.
The patient does not have a palpable bladder, nocturnal enuresis, stones or UTIs, so a renal function test is not necessary.
Alpha-blocker therapy is the best form of management for patients at high risk of cardiovascular side-effects and with only mild symptoms. This patient may never progress to requiring medication and thus avoid all the associated side-effects.
At this stage, obtaining a flow rate and post-void residual estimation may be premature and will be dictated by your comfort in interpreting these tests and their availability. They are not necessary in men with mild symptoms but they may make assessment of disease progression more objective.
A 5-alpha reductase inhibitor will be a treatment option to consider in the future if the symptoms begin to deteriorate and he has a large prostate or raised PSA >1.4ng/ml.
Section 6: Evidence base
- The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Proscar Long-Term Efficacy and Safety Study Group (PLESS). N Engl J Med 2003; 349: 2387-98.
Randomised placebo-controlled double-blind trial assessing finasteride versus placebo in 3,040 men with symptoms due to BPH over four years. Finasteride treatment led to a 50% reduction in men developing acute retention and needing surgery.
- The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: four-year results from the CombAT study. Eur Urol 2010; 57: 123-31.
Randomised double-blind parallel group study assessing tamsulosin and dutasteride alone or in combination in men with symptoms of BPH over four years. Combination therapy was superior to monotherapy at reducing risk of progression.
Good assessment recommendations on page 28.
- Practical Urology: essential principles and practice: Chapter 16. ISBN 978-1-84882-033-3
- British Association of Urological Surgeons – a good page on what patients might ask their primary care physician. Also contains videos on what prostatic surgery entails.
|CPD IMPACT: EARN MORE CREDITS|
These further action points may allow you to earn more credits by increasing the time spent and the impact achieved.
- Mr Altaf Mangera is a registrar and Mr Christopher Chapple is honorary professor of urology and consultant urological surgeon at the Royal Hallamshire Hospital, Sheffield
- Declaration of interest: Mr Chapple was chairman of the recent NICE guidelines: NICE. Lower urinary tract symptoms. The management of lower urinary tract symptoms in men. CG97. NICE, London, 2010.
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