Health 24 - Prostate, Enlarged prostate

The prostate is a walnut-shaped gland situated immediately below the bladder and in front of the rectum. It completely surrounds the upper part of the urethra, the tube running from the bladder to outside the body.

The prostate contributes �0.5ml to the volume of ejaculate, supplying nutrients to the sperm. Together with the bladder neck, the prostate forms a genital sphincter ensuring antegrade ejaculation, causing semen to be expelled to the outside rather than running back into the bladder.

Benign prostatic hyperplasia (BPH) is the non-cancerous enlargement of the prostate gland. The development of BPH is dependent on the male hormones testosterone and dihydrotestosterone. Over time it occurs to a greater or lesser degree in all men with functioning testicles and normal prostates.

The enlargement of the prostate distorts the urethra, obstructing the flow of urine from the bladder and leading to symptoms of an obstructive or irritative nature.

Symptoms are not directly related to prostate size. Some very large glands are completely asymptomatic whereas some very small glands can be severely symptomatic.

Clinically significant BPH is present in 50% of men aged 60-69 years, with �50% of these men needing treatment. The lifetime risk of needing surgery to the prostate gland is � 1 in 10.

Cause

The prostate gland consists of glandular and stromal elements. The stroma contains smooth muscle and connective tissue. BPH involves an increase of all elements of the gland, but with a relatively greater increase of prostatic stroma.

The prostate requires male hormones (testosterone and dihydrotestosterone) to grow. These hormones do not cause BPH, but are necessary for it to develop.

Aging and male hormones are the only proven risk factors for developing BPH. Any man with a normal prostate and functioning testes will develop BPH if he lives long enough.

The testes produce 95% of testosterone found in the body. Testosterone is converted to dihydrotestosterone in the prostate gland. The prostate gland is much more sensitive to dihydrotestosterone than testosterone. An enzyme called 5-alpha reductase mediates this conversion of testosterone to its active form. 5-Alpha reductase is specific to the prostate gland (it is not found anywhere else in the body) and can be manipulated medically (see treatment section).

Dihydrotestosterone causes the formation of growth factors within the prostate gland, which in turn lead to an imbalance between cell growth and programmed cell death (apotosis).

The net effect of all this is a slow progressive enlargement of the prostate gland over time. While the majority of older men have clinically enlarged prostate glands, this per se does not necessarily lead to symptoms or complications.

BPH can cause symptoms due to its effect on the prostate itself, or due to its obstructive effect on the bladder outlet (see symptoms).

Symptoms

BPH can be asymptomatic or symptomatic. Symptoms can be related to the obstructive effect of prostate enlargement itself, to secondary effects of the obstruction on the bladder, or to the complications of BPH.

Obstruction of the bladder outlet can have variable effects on the bladder. It can lead to thickening of the bladder muscle and bladder muscle instability. Bladder instability is thought to account for irritative symptoms.

Obstruction can also lead to, or worsen, poor bladder contraction. This can lead to obstructive symptoms and poor bladder emptying. Both bladder instability and poor bladder contraction are associated with aging per se. Obstruction will accentuate both these effects of aging.

Obstructive symptoms

Irritative symptoms

Symptoms of complications

Prevalence

There is no accepted definition of what comprises BPH. The first microscopic changes of hyperplasia tend to develop in the prostate around age 35. All men eventually develop BPH if they live long enough.

Only �50% of men with histological (microscopic) evidence of BPH will have symptoms related to their prostatic enlargement. An enlarged prostate gland will not necessarily cause obstruction or symptoms.

The clinical syndrome (symptoms and signs) related to prostatic enlargement goes by many different names, including BPH, LUTS (lower urinary tract symptoms), prostatism and bladder outflow obstruction.

50% of men aged 51-60 years and 90% of men over 80 years have histological BPH. However, only 25% of 55-year-old men and 50% of 75-year-old men will have bothersome symptoms related to their prostatic enlargement.

Course

The natural history of untreated BPH is variable and unpredictable. There is little reliable information in the medical literature. It is clear, however, that BPH is not necessarily a progressive disease.

Many studies indicate that in up to 30% of patients symptoms may improve or disappear over time. In �40% of patients symptoms stay the same and in 30% of patients symptoms get worse. �10% of untreated patients will eventually develop retention of urine. 10-30% of untreated patients eventually need surgery for their prostatic enlargement.

Risk Factors

Any normal man will develop BPH if he lives long enough. Time and male hormones (dihydrotestosterone and testosterone) are the only proven risk factors for developing BPH.

Prostate cells are much more sensitive to dihydrotestosterone than testosterone itself. An enzyme specific to the prostate, 5-alpha reductase, converts testosterone to dihydrotestosterone. Men who are castrated in their youth, or who lack 5-alpha reductase, do not develop BPH.

Recent studies indicate a probable genetic link for BPH. A male with a first degree relative who has had surgery for BPH has a four times' increased lifetime risk of needing prostate surgery himself. This genetic link is especially strong for men under 60 years of age with large prostates.

Some studies indicate that male hormone receptors (androgen receptors) may be increased in BPH cells. The role of environmental factors such as diet, obesity and an industrialised environment is not entirely clear.

Oriental men (especially the Japanese) have a low incidence of BPH. The oriental diet, which is high in phyto oestrogens, may have a protective effect.

When to see a Doctor

The acute (sudden) inability to pass urine is painful and will necessitate a hospital or doctor�s visit. Retention of urine can also come on slowly with a progressively worsening stream and eventual overflow incontinence.

In this scenario the bladder never empties properly, which can lead to obstructive kidney failure and other complications such as infections or stones.

Blood in the urine should never be assumed to be due to prostatic enlargement unless all other more serious causes, such as bladder cancer, have been ruled out.

Any man over 50 years should have a yearly prostate check to rule out prostate cancer. Black men, who are at higher risk for this kind of cancer, and men with a positive family history of prostate cancer should start their prostate checks at age 40. The aim of yearly prostate checks in is to diagnose prostate cancer early, when it is still curable.

Early prostate cancer is usually completely asymptomatic. Men who have had previous surgery for BPH (i.e. TURP or open prostatectomy) are not exempt from the risk of prostate cancer.

Prostate cancer classically develops in the outer part of the gland, which is not removed during operations for BPH.

Visit preparation

You may be asked to fill in a questionnaire to help assess the severity of your symptoms (symptom score). The physical examination should include a digital rectal examination of the prostate gland.

The health professional will usually require a urine sample and may ask you to pass urine into a machine to measure the flow rate. It is a good idea not to empty your bladder shortly before the appointment.

Diagnosis

Diagnosis of BPH is made based on medical history, physical examination and some confirmatory special tests.

History:

Symptoms of BPH can be grouped as either obstructive or irritative (see symptoms). Diagnosis cannot be made on symptoms alone as many diseases can mimic the symptoms of BPH. A careful history will give clues to conditions other than BPH as the cause of symptoms.

Diseases that can mimic BPH:

Urethral stricture can result from previous trauma, instrumentation (i.e. catheter) or infection such as gonorrhoea. Blood in the urine may indicate bladder cancer. Burning and pain with passing urine may indicate infection or stones.

Diabetes can cause frequent passage of urine, as well as poor bladder emptying due to its effect on bladder muscle and nerve function.

Symptom scores are checklists used to assess the severity of prostatic symptoms and can help to determine if an individual needs further evaluation or treatment. The most widely used is the American Urological Association symptom index.

Symptoms are classified according to the total score as mild (1-7), moderate (8-19) or severe (20-35). Generally, no treatment is needed if symptoms are mild. Moderate symptoms usually require some form of treatment and severe symptoms most often lead to surgical treatment.

Physical examination:

On physical examination the doctor will assess the patient's general health and examine the abdomen for the presence of a full bladder. A digital rectal examination will be performed to assess the size, shape and consistency of the prostate gland.

This examination involves the insertion of a gloved finger into the rectum. The prostate gland is situated immediately adjacent to the anterior rectal wall and is easily palpable in this manner. The test is mildly uncomfortable, but should not be painful. BPH classically leads to smooth, rubbery enlargement, whereas prostate cancer causes hard irregular nodular enlargement of the prostate.

Unfortunately prostate size alone correlates poorly with symptoms or obstruction. Many large prostates cause no symptoms or obstruction at all, and some very small prostates can lead to severe obstruction with symptoms and/or complications.

An enlarged prostate per se is not an indication for treatment. In patients who do need treatment, the size of the gland can influence which treatment option is selected. A neurological examination is indicated if the history suggests a possible neurological cause for the symptoms.

Special tests:

Special tests are used to confirm diagnosis, rule out other causes of symptoms, prove or disprove obstruction and identify complications related to the obstruction.

Minimum recommended evaluation for BPH:

Optional tests:

Simple urine analysis can be performed in the office with dipstix. If this indicates possible infection a urine culture should be obtained. If the urine contains blood this should be further investigated to rule out other causes.

A urine flow rate is performed by asking the patient to pass urine into a machine, which measures urine flow rate. Most machines measure the volume of urine, the maximum flow rate and the time taken to empty the bladder. For a flow rate test to be of value the patient needs to pass at least 125-150 ml of urine at one time.

The most useful parameter is the maximum flow rate or Q-max, measured in millilitres per second. Although flow is only an indirect measure of obstruction, most patients with a flow rate less than 10 ml/second will prove to have bladder outflow obstruction, whereas most patients with a flow rate of more than 15 ml/second will not have evidence of obstruction.

Patients with a low flow rate prior to surgery tend to do better following surgery as compared to those with higher initial flow rates. A low flow rate however cannot be used to distinguish between obstruction and poor bladder muscle function as the cause of poor flow.

Serum creatinine is measured on a blood sample and is a fair reflection of renal function. Creatinine is one of the waste products excreted by the kidneys. If serum creatinine level is elevated due to bladder outflow obstruction, it is prudent to drain the bladder with a catheter and allow the kidneys to recover prior to embarking on prostate surgery.

Pressure/flow urodynamic testing is the most accurate method of proving obstruction of the bladder outlet. It involves simultaneous measurement of pressure within the bladder and flow of urine. Obstruction is characterised by high pressure and low flow. It is an invasive test with probes inserted into the bladder and rectum. Most authors do not recommend routine measurement of pressure/flow urodynamics for patients with prostate symptoms. It can however be invaluable in cases that are not clear-cut.

Indicators for pressure flow analysis:

Serum PSA is elevated by BPH, but more so by prostate cancer. The routine use of serum PSA as a screening test for prostate cancer is controversial. The American Urological Association and most urologists recommend annual PSA testing in men over 50 years with a 10-year life expectancy.

Black men and men with a positive family history of prostate cancer should start PSA testing at age 40. PSA levels rise before prostate cancer becomes clinically evident, enabling early diagnosis and treatment while the disease is still curable.

Abdominal ultrasound can be useful to assess the kidneys for hydronephrosis (swelling and dilatation) and to measure the post void residual, that volume which remains in the bladder after the patient has passed urine. Residual urine volume does not correlate well with other symptoms and signs of prostatism and does not predict the outcome of surgery.

It is uncertain whether large post void residual volumes indicate impending bladder or renal damage. Most authors feel that patients with large post void residual volumes should be monitored more closely if they opt for non-surgical therapy.

Kidney impairment due to obstruction is associated with dilatation (hydronephrosis). In patients with raised serum creatinine, ultrasound can confirm whether the kidney impairment is due to obstruction or not.

Transrectal ultrasound of the prostate gland is not routinely indicated in patients with BPH. It can measure prostate volume (size) very accurately. Its main role is in guiding prostate biopsies in cases of suspected prostate cancer.

Treatment

The main treatment options are watchful waiting, medication and surgery. In those patients who are totally unfit for surgery and for whom medication has failed, long-term indwelling catheters, self-intermittent catheterisation or internal urethral stents (see later) can be used. The complications of BPH are generally regarded as indicators for surgery. Patients who have suffered complications related to BPH are not candidates for watchful waiting or medication.

Home

Watchful waiting is a strategy of no immediate treatment with follow-up medical checks at regular intervals. The natural history of BPH is not necessarily progressive. Symptoms remain stable or may even get better in many patients. Watchful waiting is suitable for patients with minimal symptoms and no complications. The patients can be reviewed � yearly with symptom scores, physical examination and flow rate analysis. During watchful waiting patients should avoid tranquilisers and over-the-counter cold and sinus remedies, which can worsen symptoms and may even lead to urinary retention.

Several simple measures can improve symptoms related to BPH. Alcohol and caffeine should be taken in moderation, especially in the evening prior to going to bed. Tranquilisers and anti-depressants impair bladder muscle function and effective bladder emptying. Cold and flu remedies usually contain decongestants, which cause increased tone in smooth muscle fibres in the bladder neck and prostate, leading to worsening symptoms.

Phytotherapy refers to the use of plant extracts for medicinal indications. These treatments for BPH-related symptoms have received attention in the popular press recently. Most widely known is the extract of serenoa repens (commonly known as Saw Palmetto). The mechanism of action of these phytotherapies is unknown and their effectiveness unproven. Suggested modes of action include an anti-inflammatory effect to reduce prostate swelling and possible inhibition of hormones controlling the growth of prostatic cells. It is highly possible that their only action is as a result of the placebo effect.

Medication

Two types of medication are effective in the treatment of BPH, namely alpha-blockers and 5-alpha reductase inhibitors.

The prostate and bladder neck contain large numbers of smooth muscle cells. The tone in these muscle cells is under sympathetic (involuntary) nervous system control. The receptors at the nerve endings are called alpha-receptors. Alpha-blockers are drugs that block these alpha-receptors, thus decreasing the tone in the prostate and bladder neck. The net effect is an increase in flow rate and an improvement in prostatic symptoms. Alpha-receptors are found elsewhere in the body, especially in blood vessels. The original alpha-blockers were designed to treat high blood pressure. Not surprisingly, the most frequent side-effect of alpha-blockers is orthostatic hypotension (dizziness upon standing due to a fall in blood pressure).

Commonly used alpha-blockers are prazosin (Minipress�), doxazosin (Cardura�), terazosin (Hytrin�) and tamsulosin (Flomax�). Tamsulosin is a selective alpha 1A receptor blocker, specifically designed to block the sub-type of alpha-receptor found predominantly in the bladder and prostate.

Alpha-blockers are effective in patients without absolute indications for surgery and post void residual volumes of less than 300ml. Most studies indicate a 30-60% reduction of symptoms and a moderate increase in flow rate. All four alpha-blockers are effective at therapeutic dosages. The maximal effect is obtained within two weeks and the response is durable. Ninety% of patients tolerate the treatment well. The main reasons for discontinuing treatment are dizziness due to hypotension and perceived lack of efficacy. No direct comparative studies between the various different alpha-blockers have been performed, and claims of relative superiority cannot be justified. Treatment usually needs to be life-long. A less common side effect is abnormal or retrograde ejaculation, which occurs in 6% of patients taking tamsulosin.

The enzyme 5-alpha reductase converts testosterone to its active form, namely dihydrotestosterone within the prostate gland. Finasteride (Proscar�) blocks this conversion. In some men finasteride can relieve BPH symptoms, increase urinary flow rate and shrink the size of the prostate gland. The improvements, however, are usually only modest and take up to six months to achieve. Recent studies indicate that finasteride may be more effective in men with bigger prostates and have little effect in men with smaller glands. Finasteride does reduce the incidence of urinary retention and the need for prostatic surgery by 50% over a four-year period.

Due to its cost, moderate efficacy and long time to achieve maximal benefit, finasteride is not widely used for BPH treatment in South Africa. Side-effects of finasteride include breast enlargement (0.4%), impotence (3-4%), decreased ejaculate volume and 50% reduction of PSA levels.

Surgery (Prostatectomy)

Prostatectomy is the most commonly performed urological procedure. About 200,000 prostatectomies are performed annually in the USA. A prostatectomy for benign disease (BPH) involves removal of only the inner portion of the prostate. This operation differs from radical prostatectomy for cancer in which all prostate tissue is removed. Prostatectomy offers the best and fastest chance of improving BPH symptoms, but may not alleviate all irritative bladder symptoms. This is especially true for men over 80 years of age, where bladder instability is thought to account for a large proportion of symptoms.

Transurethral resection of prostate (TURP)

This procedure is still considered the �gold standard� of BPH treatments against which all other treatment options are measured. TURP is performed using a resectoscope, which is passed through the urethra into the bladder. A wire loop carrying an electrical current cuts the prostatic tissue away from the inside. A catheter is left in place for one to two days and hospital stay is usually about three days. TURP is associated with little or no pain and full recovery can be expected by three weeks after surgery.

Marked improvement occurs in 93% of men with severe symptoms and 80% of those with moderate symptoms.

As in TURP, an instrument is passed into the bladder. An electrical wire knife is used instead of a loop, and one or more cuts are made into the prostate gland to relieve pressure on the urethra. Little or no prostate tissue is removed. In men with small prostates (< 30g), results of prostatotomy are similar to TURP, but it takes much less time to perform and has fewer complications. The incidence of retrograde ejaculation is much lower than with TURP.

This modification of TURP is also performed with a resectoscope through the urethra. However, instead of cutting away the tissue, a more powerful electrical current is applied to the prostate, resulting in vaporisation of tissue, with minimal bleeding. Possible advantages include shorter catheter time, shorter hospital stay and lower cost than TURP or laser prostatectomy.

Very large prostates are less suitable for TURP, due to the high incidence of complications associated with longer resection times. Open prostatectomy is the procedure of choice for prostates greater than 70-80g. A transverse lower abdominal incision is used to expose the bladder and prostate. The prostate capsule is incised and the BPH tissue is enucleated, leaving the prostatic capsule behind. Alternatively, the bladder itself is opened and the prostate enucleated via the bladder. One bladder catheter is placed via the urethra and a second via the lower abdominal wall. The catheters are left in for about five days. The results from open prostatectomy are very good, but it is a more major operation than TURP. Hospital stay and recovery period are longer and the complication rate slightly higher. However, it is a very effective way to remove all BPH tissue and very few patients fail to void adequately afterwards.

Despite the success of TURP there has been a constant search for a less invasive, safer and cheaper treatment option, which can be performed as a day case, preferably under local anaesthesia. A variety of energy sources have been applied to the prostate gland to cause local heat generation and subsequent sloughing of prostate tissue. These include laser, microwave thermotherapy, high intensity focused ultrasound, radiofrequency thermotherapy and transurethral needle ablation of the prostate (TUNA). All of these treatments trade less intra-operative complications for reduced efficacy and increased post-operative bother. Hospital stay is shorter than with TURP, but catheter times are longer and many patients end up needing secondary treatment, usually in the form of TURP. Various laser treatments can be used on the prostate gland. Newest and most promising is holmium laser prostatectomy, which is similar to TURP in that the prostatic tissue is actually removed. Blood loss is reportedly less with holmium laser than with standard TURP.

Some patients are unfit for any kind of surgical intervention. In this case, intra-urethral stents can be placed inside the prostatic urethra to keep it open, allowing the patient to void normally. Stents can be inserted under local anaesthetic. Short-term results are good, but migration and other complications lead to stent removal in 14-33% of cases. Although long-term indwelling catheters are best avoided, sometimes they are the only viable option in ill, frail or bedridden patients. An alternative is intermittent clean catheterisation by the patient himself or a carer.

Prevention

There is no viable way of preventing the development of BPH. Whether long-term finasteride treatment, starting before BPH is clinically evident, will significantly alter the disease process of BPH is unclear.

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