Benign prostatic hyperplasia

Benign prostatic enlargement

What is benign prostatic hyperplasia?

Benign prostatic hyperplasia (BPH) is an increase in size of the prostate gland without malignancy present and it is so common as to be normal with advancing age. It seems likely that the nature of BPH is a failure of apoptosis (natural programmed death of cells) and that some of the drugs used to treat it may induce that process.¹

The prostate secretes about 20-30% of the volume of seminal fluid. It is a hormone-dependent gland and BPH does not occur in castrated men.

It should be borne in mind that lower urinary tract symptoms (LUTS) and BPH are not synonymous. Prevailing European guidelines suggest that because BPH is so common in older men, it should not be looked on as the only possible pathology in patients presenting with LUTS. The doctor assessing a patient with LUTS should take an holistic view bearing in mind the full range of causes and the possibility of co-existing morbidities.²

The term benign prostatic hypertrophy is also used but is technically incorrect. Hypertrophy means enlargement of the components without an increase in their numbers as happens with muscle fibres. Hyperplasia is an increase in the number of the components and this is typical of glandular enlargement, such as occurs in BPH.

How common is benign prostatic hyperplasia? (Epidemiology)

BPH affects the quality of life of about 40% of men in their fifth decade and 90% of men in their ninth decade.² It is unusual before the age of 45 and affects Black men more significantly than white men, possibly due to higher testosterone levels, 5-alpha-reductase activity, androgen receptor expression and growth factor activity.

Studies have shown significant correlation between LUTS and increased prostate volume.^{3 45} Another study found that the mean length of prostate increased faster than the height and width, especially after the age of 60 years. The transitional zone volume and transitional zone length had a higher correlation with the International Prostate Symptom Score (I-PSS) than total prostate volume.⁶

The prostate increases in size with passing years - prostate volume increases by between 2 and 2.5% per year. ⁵

Prostate volume is higher in Western populations than those in other areas, particularly South East Asia. However, severity of symptoms does not necessarily reflect prostate volume as Indian men tend to report more symptoms than men from Western countries.⁵

Risk factors for benign prostatic hyperplasia⁵

• Diabetes. Diabetes itself, and particularly the use of insulin, appears to increase the risk of BPH as well as other LUTS.

• Diet. Alcohol, caffeine and high dose vitamin C supplementation all appear to increase the risks of BPH. Diets higher in beta-carotene, carotenoids and vitamin A appear to be protective.

• Genetic factors. First degree relatives of people with BPH are four times more likely to develop BPH.

• Localized inflammation.

• Obesity. The exact aetiology is unknown but this has been shown in observational studies.

• Metabolic syndrome. BPH is more common in people with metabolic syndrome but causation has not been established.

Symptoms of benign prostatic hyperplasia (presentation)

History should focus on a number of specific features that are typical of the disease.⁷ This should be followed by the I-PSS ⁸ to give an assessment of the effect on the quality of life.

• Urinary frequency is often a presenting symptom. Ask how many times a day he needs to void and how often he has to rise at night. Ask also if he passes small or large volumes of urine each time. When enquiring about urinary frequency, it is necessary to distinguish frequent passage of small volumes from polyuria. To this end it may be helpful to complete a frequency/volume chart.

• Urinary urgency may occur and manifests as a need to pass urine quickly for fear of incontinence.

• Hesitancy occurs when he has to stand at the toilet for a while before he can initiate micturition. There is usually a poor stream and dribbling of urine too and he may stop during the act.

• Incomplete bladder emptying gives the sensation of still having urine in the bladder, no matter how often he goes. He may even be able to pass more immediately after he has finished.

• There may be a need to push or strain, increasing the risk of micturition syncope.

The I-PSS is a quantitative and validated technique based on eight questions and a further quality-of-life question. The results are summated to give a figure for the degree of trouble caused by the condition.

The I-PSS is free for the use of individual clinicians and non-funded research. The results are scored and severity of the symptoms is classified according to the score:

Interpretation of I-PSS score

Examination

Abdominal examination

Examination of the abdomen includes checking for a palpable bladder. This may indicate chronic outflow obstruction or a neurogenic bladder. To exclude the latter, an enquiry about motor or sensory loss along with checking knee and ankle jerks and plantar responses should suffice. Any further abnormalities require a full neurological history and examination.

Digital rectal examination

Digital rectal examination (DRE) includes noting the tone of the anal sphincter and the pelvic floor. It may be poor with a neurogenic bladder. The size of the prostate is assessed.

Urologists report their findings in terms of the size of the prostate, a normal gland in a young adult weighing about 20 g. A useful guide for those less familiar with prostates is that a finger's breadth represents about 15 to 20 g and so a gland that is three fingers in breadth across is 45 to 60 g.

Symptoms are unusual below two fingers in breadth. It is also important to note the texture and contour of the gland. It should be firm but not hard, and smooth without nodules. The median sulcus should be clearly defined. A gland that is hard rather than firm, nodular and lacks a clear median sulcus suggests carcinoma of prostate.

Diagnosing benign prostatic hyperplasia (investigations)⁷

Urine

Check urine by dipstick and send MSU for microscopy and culture.

Blood

• Routine blood tests include:

  • U&E and creatinine.

  • FBC.

  • LFTs.

  
  Abnormal LFTs may indicate other disease. Isolated elevation of alkaline phosphatase can occur:

  • If the prostate is malignant and has metastasised to bone.

  • In an elderly person, where it may represent undiagnosed Paget's disease of bone.

• PSA is elevated with a large, benign prostate. A combination of clinical examination and PSA levels may be a better way of attempting to differentiate between a benign and malignant prostate gland, although evidence to support this may be lacking.⁹ It should be recognised that normal PSA values change with age:¹⁰

• PSA testing should be carried out at least 72 hours after the last ejaculation, 48 hours after vigorous exercise and a week after a DRE, although evidence for this is not strong.¹¹

There are no age-specific reference limits for men older than 80 years of age. Clinical judgment should be used when deciding on referral.¹¹

Patients sometimes expect a test to give a simple affirmative or negative answer and so a link to help understand the PSA test may be of value. A high result may occur in benign disease and may be associated with an increased risk of having LUTS requiring treatment.¹²

Imaging

Imaging may also be necessary if there is any suggestion of urinary tract obstruction.¹³

Ultrasound examination of the prostate is increasingly used to assess the prostate volume.

The European Association of Urology suggests that post-void residual bladder volume should be part of any routine assessment of male LUTS.² Pre- and post-micturition ultrasound scans can be used to assess any residual urine following voiding and is readily available in primary care.

Other investigations

• Any uncertainty about diagnosis requires a referral to urology where further investigations may be required.

• Further investigations that may possibly be required include assessment of urine flow rate . It should be used as a baseline before embarking on any treatment, whether medical or surgical. The maximal flow rate (Qmax) is the single best measurement but a low Qmax does not help to differentiate between obstruction and poor bladder contractility. More detailed analysis requires a pressure flow study. A Qmax value over 15 mL/second is usually considered normal. A Qmax below 7 mL/second is accepted as low. Results can vary according to effort and volume and so the usual compromise is to obtain at least two readings with at least 150 mL of urine each time.

• Pressure studies are invasive but may be necessary if there is suspected bladder neck obstruction. A voiding pressure above 60 cm water with a Qmax of under 15 mL/second is regarded as diagnostic.

• Cystoscopy may be useful if urethral stricture is suspected. This may follow prolonged indwelling catheter or gonococcal urethritis. It may also be used if a lesion in the bladder is suspected.

Indications for referral

In September 2020 and more recently in January 2021, NICE provided updated guidance on suspected cancer recognition and referral. There are no specific changes in these versions that relate to prostate cancer.¹⁴

NICE recommends referral for the following:

• Acute retention of urine (admit immediately).

• Acute kidney injury (admit immediately).

• Visible haematuria (depending on age and other symptoms) - urgent cancer referral.

• Suspicion of prostate cancer based on the finding of a nodular or firm prostate, or a raised PSA level, or both - urgent cancer referral.

• Chronic urinary retention with overflow or night-time incontinence - urgent cancer referral.

• Recurrent UTI.

• Microscopic haematuria.

• Failure to respond to treatment in primary care with poor quality of life as assessed by the I-PSS.

Differential diagnosis

• Bladder tumours.

• Bladder stones.

• Bladder trauma.

• Chronic pelvic pain.

• Chronic prostatitis.

• Detrusor instability.

• Interstitial cystitis.

• Neurogenic bladder.

• Prostate cancer.

• Radiation cystitis.

• Urethral strictures.

• Urinary tract infection (UTI).

• LUTS due to heart failure or diabetes. ¹⁵

Management of benign prostatic hyperplasia^{2 14}

See also the separate Lower urinary tract symptoms in men article.

• If symptoms are minimal, 'watchful waiting' (WW) is the most judicious option, provided that malignancy has been excluded.¹⁶ One study found that WW was more readily used by specialist than by primary care physicians.¹⁷ The three key components which seem to contribute to the effectiveness of this approach are reassurance, education and monitoring.

• Several drugs have been shown to be useful to control the condition.

• A trial of medical therapy may still be followed by surgery, if required.

• Irrespective of the mode of management chosen after discussion with the patient, there should be periodic follow-up to assess progress, as the natural history is a tendency for symptoms to worsen.

• Complications, as discussed at the end, may necessitate referral, even as an emergency.

• There is some evidence supporting the use of lifestyle advice along with other modalities of treatment. BPH has been related to factors such as obesity and thus it is probably good to counsel patients on healthy diet regimens and involvement in exercise programmes if possible.¹⁸

Medication ⁷

• Alpha-adrenergic antagonists, or alpha-blockers, reduce the tone in the muscle of the neck of the bladder. They should be offered to men with moderate-to-severe voiding symptoms (corresponding to an I-PSS of 8 or more). There are alpha-1 receptors that are subdivided into types 1a, 1b and 1c. The alpha-1a is predominant in the prostate gland, bladder neck and urethra and the most selective drug available is tamsulosin.¹⁶ Prescribers of tamsulosin should be aware of the existence of intra-operative floppy iris syndrome, a condition which causes the iris to 'billlow out' during cataract surgery. This does not usually affect the long-term outcome but it can cause pain and prolong the recovery period. If aware, ophthalmologists can use techniques to minimise the risk of this occurring, so it is important that ophthalmologists review the lists of medication that patients are on.¹⁹

• Less selective alpha-blockers include doxazosin, terazosin, prazosin, alfuzosin and indoramin. The less specific effects may sometimes be beneficial. For example, if the patient has BPH and hypertension, one drug may be beneficial for both.

• 5-alpha reductase inhibitor (5-ARI) drugs block the synthesis of dihydrotestosterone from testosterone and can reduce symptoms - eg, finasteride and dutasteride. Whilst they are effective, it may take several months before benefit is noted. Unlike alpha-blockers, they have been shown to reduce the long-term risk (>1 year) of acute retention or need for surgery.

• For patients with bothersome moderate-to-severe LUTS not responding to monotherapy, an alpha-blocker plus a 5-ARI can be considered. Treatment should be continued for at least one year.

• There are a number of dietary supplements that are used in BPH. They are not available on FP10 but may be bought by the patient. Establishing an evidence base for the effectiveness of these products has been difficult due to variations in methodological techniques. One review of the literature reported some evidence for the effectiveness of beta-sitosterol, Pygeum africanum and Cernilton® but not for several other compounds.²⁰

• Daily tadalafil has been shown to be of benefit.²¹ Its use has historically been limited by cost but is licensed for this indication.²²

Certain caveats should be observed:

• Avoid alpha-blockers in those with postural hypotension or micturition syncope.

• 5-ARIs may have an adverse effect on sexual performance and direct questioning about sexual history is needed. Problems include decreased libido, ejaculation disorder and erectile dysfunction, which may continue after the medication has been stopped. Generally, adverse effects are less than with alpha-blockers.

• 5-ARIs are teratogenic and can be absorbed through the skin and are excreted via semen. Women of child-bearing age should not touch them and condoms should be worn during sexual intercourse with women of child-bearing age.

• Caution is required when prescribing 5-ARIs to men with hepatic impairment.

• Studies suggest that alpha-blockers continue to exert efficacy for at least four years.

• Due to their slow onset of action, 5-ARIs should be continued longer term.

Surgery

Surgery is usually reserved for those with a large prostate gland or failure to respond to an adequate trial of medical therapy.^{2 23}

• Surgery is required if there is acute urinary retention, failed voiding trials, recurrent gross haematuria, UTI, renal insufficiency due to obstruction or failure of medical treatment.

• Transurethral resection of the prostate (TURP) is the standard technique. A working sheath is placed in the urethra through which a hand-held device with an attached wire loop is placed. A cutting diathermy is run through the loop so that it can be used to shave away prostatic tissue. When successful, it is an excellent operation that does not involve entering the abdomen but it can have complications. Bleeding may be difficult to control. Irrigating fluid may be absorbed into the circulation via cut veins. An indwelling catheter is required until bleeding has stopped. Urethral stricture can occur. There can be retrograde ejaculation after operation or damage to the nerves can cause erectile dysfunction.

• The UroLift System is a minimally invasive procedure, which should be considered as an alternative to TURP and holmium laser enucleation of the prostate (HoLEP). It can be done as a day-case or outpatient procedure for people aged 50 and older with a prostate volume between 30 and 80 ml. Evidence supports the case for adopting the UroLift System for treating lower urinary tract symptoms of BPH.²⁴ The UroLift System relieves lower urinary tract symptoms, avoids risk to sexual function, and improves quality of life.

• HoLEP is equally effective, but UroLift is more cost-effective.

• Rezum®²⁵ has been approved by NICE as an option for treating lower urinary tract symptoms secondary to BPH. Rezum® technology uses water vapour to destroy excess prostate tissue, with the aim of relieving symptoms. The procedure can be carried out as a day case and is cost-saving compared to TURP. The incidence of sexual dysfunction after treatment with Rezum® was low, with a few people reporting a decrease in ejaculatory function but little change in erectile function.

• Estimated prostate size smaller than 30 g: transurethral incision of the prostate (TUIP) or transurethral needle ablation (TUNA) can be offered as an alternative to TURP for patients wishing to avoid, or who are unfit for, more invasive surgery. Both treatments, however, have a higher recurrence rate than TURP. If the prostate size is larger than 80 g, this narrows the options to TURP, TUVP or HoLEP.

• It should be noted that surgical options are unlikely to be definitive procedures.

• Newer techniques such as prostate artery embolisation have been shown to be safe and effective and are increasingly being used.²⁶

Complications of benign prostatic hyperplasia

Bladder outlet obstruction can result in:

• Urinary retention: this may be precipitated by anticholinergic drugs, including tricyclic antidepressants, opiates and diuretics.

• Recurrent UTI, especially with incomplete emptying.

• Impaired kidney function: progression to chronic kidney disease is much rarer now.

• Bladder calculi (may present as ongoing LUTS or recurrent infections).

• Haematuria - may be microscopic or macroscopic.

BPH is not considered to be a precursor of prostate cancer. It is likely that, although BPH may not make prostate cancer more likely to occur, it may increase the chance of diagnosing an incidental cancer.²⁷