Diseases

Benign Prostatic Hyperplasia

Benign prostatic hyperplasia affects the prostate gland and makes it dificult for elderly men to pass urine. It is very common. Research is continuing to understand the causes of BPH and to develop medicines to help relieve this distressing condition.

What is benign prostatic hyperplasia? Top

Benign prostatic hyperplasia (BPH) is an enlargement of more than 30cc in volume of the prostate gland, constricting the urethra and making the passing of urine difficult.

This increases the risk of urinary retention and of the onset of chronic prostatitis due to bacterial infection, mainly with Escherichia coli, Enterococcus faecalis and Staphylococcus epidermidis. The development of benign prostatic hyperplasia is linked to an age-related decrease in male hormones.

Who does BPH affect? Top

In Europe, BPH is the commonest cause of urination difficulties in men. However, prostate enlargement does not always give rise to symptoms and, even when it does, only about half of those affected seek medical help.

Some prostate enlargement is apparent in 75 per cent of men over 50 and clinical signs may be apparent in 30 per cent of individuals in their 60s, rising to almost 100 per cent in those over 90 years of age. Bacterial prostatitis accounts for an estimated two million outpatient visits yearly.

 

Male anatomy showing the location and structure of the prostate gland

Present treatments Top

Acute urinary retention often needs catheterisation. Under normal circumstances the catheter stays in place for some days. An unsuccessful trial after removal of the catheter may lead to prostate surgery. While surgical intervention may ultimately be required, useful medicines are available which provide symptomatic relief for BPH.

The major class of medicines used for this purpose is the alpha-adrenoreceptor antagonists, which block receptors in the muscles that control emptying of the bladder, improving urine flow.

Selective alpha-adrenoreceptor blockers have a rapid onset of action and are indicated for symptomatic therapy. They are generally well tolerated, although some may cause dizziness or interfere with blood pressure control.

Alpha-adrenoreceptor antagonists also act by relaxing prostate smooth muscle cells. Compounds that show greater relative binding affinity to prostatic alpha-1a receptors as compared to vascular alpha-1b receptors are thought to reduce the likelihood of hypotension and other side-effects associated with compounds in this class.

Relieving the symptoms, though, does not deal with an enlarging prostate. For this purpose, compounds have been introduced that inhibit type 2 of the enzyme 5-alphareductase. The enzyme converts testosterone – the male sex hormone - into the more potent dihydrotestosterone (DHT) which induces prostate enlargement.

Inhibiting this enzyme reduces DHT formation and, as a result, shrinks the enlarged prostate gland. Six months or more of usage is, however, often necessary before its full effectiveness can be judged; in addition, decreased libido and impotence may occur.

Another compound of 5-alpha-reductase inhibitor inhibits both types 1 and 2 of the enzyme, giving a particularly marked suppression of DHT formation. The type 2 isoenzyme is the dominant form of 5-alpha-reductase, type 1 accounts for 15 per cent of the concentration in the gland.

Meanwhile, combination therapy with a 5-alpha reductase inhibitor and an alphablocker is available. In clinical trials that enrolled men at increased risk of disease progression, it could be shown that the combination was more effective than either medicine alone in relieving symptoms and reducing the risk of disease progression, such as acute urinary retention and BPH-related surgery.

Bacterial prostatitis is treated with antibiotic medicines.

What’s in the development pipeline? Top

Development of more specific alpha-adrenoreceptor blockers, which show a particularly high specificity of binding, continues and clinical research on several compounds of this class is underway. Research groups are studying alpha-adrenoreceptor blockers to prevent acute urinary retention (a complication of benign prostatic hyperplasia that requires emergency treatment).

Further clinical research with 5-alpha-reductase inhibitors is concentrating on the prevention of prostate cancer. Large Phase 3 studies have been started to enrol patients at risk of the disease (with elevated prostate-specific antigen levels who are biopsy negative within six months of inclusion). These investigations will take at least several years.

A variety of other approaches is being tried. Vitamin D3 is thought to be able to reduce cell proliferation in the prostate, like 5-alpha-reductase inhibitors. However, the vitamin itself is not suitable for use as a treatment; because of its effects on the way calcium and phosphate are processed by the body. Instead, versions that do not induce excessive calcium levels have been developed.

Finally, some other hormonal approaches are being tried. Scientists are investigating a Gonadotrophin Releasing Hormone (GRH) antagonist that reduces testosterone and DHT levels and has shown improvements in symptoms in a Phase 2 trial and there are Phase 2 and Phase 3 studies ongoing with Luteinizing Hormone Releasing Hormone (LHRH) antagonists.

The longer-term future Top

Several effective medicines are now available for the treatment of the symptoms of benign prostatic hyperplasia and successful research continues into new approaches.

Further insight into the biology of the prostate and its growth regulation, as well as the development of more uro-selective and potent medications, is likely to bring future improvements in the treatment of benign prostatic hyperplasia - a condition that is likely to become even more common with the ‘greying’ of Europe’s male population over the next decades.