Benign Prostatic Hyperplasia

Benign prostatic enlargement, BPH

The term benign prostatic hypertrophy is also used but technically it is 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.

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 and that some of the drugs used to treat it may induce that process.¹ Apoptosis is the natural programmed death of cells.

The term prostatism has fallen from favour to describe the symptoms of BPH and the term lower urinary tract symptoms or LUTS is preferred. BPH, LUTS and bladder outlet obstruction are not entirely synonymous.

The prostate secretes about 70% of the volume of seminal fluid. It is hormone dependent and BPH does not occur in castrated men.

BPH affects the quality of life of about a third of men over 50 years, the numbers increasing markedly with years. Histological evidence of BPH occurs in up to 90% of men by the age of 80. It is unusual before the age of 45 and affects men of Afro-Caribbean origin at a slightly earlier age. There is little correlation between size of prostate and clinical complaints.² The prostate increases in size with passing years but at a decelerating rate. Between the ages of 31 and 50 it doubles in size every 4.5 years. Between 51 and 70 this doubling time increases to 10 years and over 70 it reaches 100 years.³

History should focus on a number of specific features that are typical of the disease. This should be followed by the International Prostate Symptoms Score (IPPS) to give a assessment of the effect on the quality of life. If surgery seems likely, and bearing in mind the age of most men who present with this condition, further questions to assess fitness for surgery may be in order. This should be followed by examination and special investigations to exclude a number of conditions that can mimic BPH.

• 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.
• Urinary urgency may occur. There is a need to pass urine quickly for fear of incontinence.
• Hesitancy is when he has to stand at the toilet for a while before he can initiate micturition. There is usually a poor stream too and he may stop during the act. There may be dribbling.
• 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.

International Prostate Symptom Score (IPSS) is a quantitative and validated technique based on 8 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 link to the International Prostate Symptom Score (IPSS) explains the system and allows the questionnaire to be used within the consultation. The results are scored and severity of the symptoms is classified according to the score:

• Examination of the abdomen includes checking for a palpable bladder. This may indicate chronic outflow obstruction or a neurogenic bladder. To exclude the latter a brief enquiry about motor or sensory loss along with checking knee and ankle jerks and plantar response should suffice.
• Digital rectal examination 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 20g. A useful guide for those less familiar with prostates is that a finger's breadth represents about 15 to 20g and so a gland that is 3 fingers breadth across is 45 to 60g. Symptoms are unusual below 2 fingers 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.
• If an elderly person is likely to need operation a brief check of the cardiovascular and respiratory systems is wise.

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 it may represent undiagnosed Paget's disease of bone.
• Acid phosphatase used to be used to assess for carcinoma of prostate but it is elevated for several days after rectal examination and is less reliable than PSA and technically difficult to assay. Nowadays it is largely of historical interest
• Prostate specific antigen (PSA) is not raised by DRE but it is elevated with a large, benign prostate. Nevertheless, Clinical Knowledge Summaries advise, "The PSA test should be done before the digital rectal examination. If this is not practicable, it is recommended that the PSA test be delayed a week."
  A combination of clinical examination and PSA levels are a better way of attempting to differentiate a benign and malignant prostate.⁴ It is also preferable to relate normal PSA to age:

Patients (and sometimes doctors) expect a test to give a simple affirmative or negative answer and so a booklet to help understand the PSA test may be of value.⁶ A high result may occur in benign disease.⁷

Imaging

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

• Abdominal ultrasound or intravenous urography may be required.
• Ultrasound examination of the prostate may be used to assess abnormal areas and possibly to guide needle biopsy.

Other investigations

• 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 differentiate between obstruction and poor bladder contractility. More detailed analysis requires a pressure flow study. A Qmax value over 15 ml/s is usually considered normal. A Qmax below 7 ml/s is accepted as low. Results can vary according to effort and volume and so the usual compromise is to obtain at least 2 readings with at least 150 ml of urine each time.
• Residual bladder volume is measured immediately after voiding. It can be estimated by passing a catheter and measuring the volume but ultrasound is comfortable, non-invasive and accurate.
• Pressure studies are rather invasive but may be necessary if there is suspected bladder neck obstruction. A voiding pressure above 60cms water with a Qmax of under 15 ml/s is regarded as diagnostic.
• Endoscopy may be required. A flexible cystoscope can be used as an outpatient procedure with a topical anaesthetic gel. It takes several minutes and 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.

• Carcinoma of prostate
• Urinary tract infection
• Interstitial cystitis can affect men too
• Bladder tumours
• Detrusor instability
• Chronic prostatitis

• If symptoms are minimal, watchful waiting is the most judicious option, provided that malignancy has been excluded.
• Other management does not always have to be surgical and a number of drugs have proved useful to control the condition and they have been reviewed.⁸
• 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.⁹
• Complications, as discussed at the end, may necessitate referral, even as an emergency.

Drugs

• Alpha adrenergic blockers reduce the tone in the muscle of the neck of the bladder. There are alpha-1 receptors that are subdivided into types 1a, 1b and 1c. The alpha-1a is predominant in the prostate, bladder neck and urethra and the most selective drug available is tamsulosin. Less selective alpha blockers include doxazocin, terazocin, 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 drugs block the synthesis of dihydrotestosterone from testosterone¹⁰ and can reduce symptoms. Finasteride and dutasteride are examples. They do work¹¹ but it may take several months before benefit is noted. They are probably preferable to alpha blockers if the prostate is large.
• There are a number of herbal agents that are used in BPH. They include: saw palmetto, beta sitosterol, rye grass, and Pygeum africanum bark extract. They are not available on FP10 but may be bought by the patient. The mode of action is unclear and varies between each. Pygeum africanum may be of value but the evidence is very limited.¹² Evidence to support other herbal products is also very limited.¹³ For those prepared to take a drug that has not been adequately tested for efficacy, toxicity or drug interactions and which can vary in potency between batches this may be an acceptable alternative. The volume of sales suggests that there is no shortage of customers. These products tends to be very popular in Germany and France and are gaining sales in North America.

Certain caveats should be observed:

• Avoid alpha blockers in those with postural hypotension of micturition syncope
• 5-alpha reductase inhibitors may have an adverse effect on sexual performance and it is unwise to assume that a man of advanced years has renounced his conjugal pleasures. However, he may be too shy to complain of the problem. Problems include decreased libido, ejaculation disorder, and erectile dysfunction. Generally, adverse effects are less than with alpha blockers.
• The evidence is based on trials of less than 5 years but in practice treatment may be needed for many more years.¹⁴

Surgery

Surgery is usually reserved for those with a large prostate or failure to respond to an adequate trial of medical therapy.

• Surgery is required if there is acute urinary retention, failed voiding trials, recurrent gross haematuria, urinary tract infection, renal insufficiency due to obstruction or failure of medical treatment.
• Open prostatectomy is reserved for those with a prostate larger than 75g, bladder stones or bladder diverticula, and patients who cannot be positioned for transurethral surgery. The inner core of the prostate adenoma is shelled out, leaving the peripheral zone behind. There may be significant blood loss requiring transfusion. Open prostatectomy usually has excellent results in terms of improvement of urinary flow and urinary symptoms.
• Transurethral resection of the prostate (TURP) is now 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.
• Minimally invasive therapies usually involve heat destruction of prostatic tissue. Via the urethra energy is transferred to destroy tissue in the form of laser,¹⁵ microwaves, radiofrequency waves, high-intensity ultrasound, and high-voltage electrical energy. They are still under development.
• Transurethral incision of the prostate (TUIP) may be suitable for those with a small prostate who are unsuitable for general anaesthesia.

Bladder outlet obstruction can result in:

• Urinary retention. This may be precipitated by anticholinergic drugs including tricyclic antidepressants or when left ventricular failure is treated with morphine and diuretic.
• Recurrent UTI, especially with incomplete emptying
• Impaired renal function. Nowadays it is rarely allowed to progress to chronic renal failure
• Bladder calculi
• Haematuria

Patients on medical treatment should have symptoms assessed every 6 months. Every year PSA and DRE should be repeated. A benign prostate can undergo malignant change. In extreme old age not only is BPH almost invariable but areas that seem to have at least carcinoma-in-situ are very common. This is probably best managed conservatively as there is little evidence that an aggressive approach is beneficial.¹⁶

NICE recommends referral for the following indications:

• Acute retention of urine (admit immediately)
• Acute renal failure (admit immediately)
• Visible haematuria (to be seen in 2 weeks)
• Suspicion of prostate cancer based on the finding of a nodular or firm prostate, or a raised prostate-specific antigen (PSA) level, or both (to be seen in 2 weeks)
• Culture-negative dysuria (to be seen in 2 weeks)
• Chronic urinary retention with overflow or night-time incontinence (to be seen in 2 weeks)
• Recurrent urinary tract infection.
• Microscopic haematuria.
• Failure to respond to treatment in primary care with poor quality of life as assessed by the IPPS.