BENIGN PROSTATIC HYPERPLASIA

What is benign prostatic hyperplasia?

Benign prostatic hyperplasia (BPH), is a non-cancerous enlargement of the prostate gland, constricting the tube leading from the bladder (urethra), making the passing of urine difficult. Its development is linked to an age-related decrease in male hormones.

Who does BPH affect?

Benign prostatic hyperplasia is the commonest cause of urination difficulties in men. Some prostate enlargement is apparent in 75 per cent of men over 50. However, prostate enlargement does not always give rise to symptoms and, even when it does, only about half of those affected seek medical help. Estimates of the number affected have varied in different surveys. Depending on definitions used, clinical signs may be apparent in 15-30 per cent of individuals in their 60s.

Present treatments and shortcomings

Several medicines are available that can control symptoms in the earlier stages of BPH, although surgical intervention may eventually become necessary. The most used are the alphaadrenoceptor alphaadrenoceptor antagonists, which block receptors in the muscles that control emptying of the bladder, improving urine flow.

Selective alpha-adrenoceptor blockers now launched in the UK are: alfuzosin (Xatral, sanofi-aventis), doxazosin (Cardura, Pfizer), indoramin (Doralese, Glaxo¬SmithKline), prazosin (Hypovase, Pfizer), tamsulosin (Flomaxtra XL, Astellas), and terazosin (Hytrin, Abbott). These compounds are generally well tolerated, although some may cause dizziness or interfere with blood pressure control.

Relieving the symptoms, though, does not deal with an enlarging prostate. For this purpose, Merck Sharp & Dohme introduced finasteride (Proscar), the first compound to inhibit the enzyme 5-alpha-reductase that converts the male sex hormone testosterone 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. However, six months or more of use is often necessary before its full effectiveness can be judged; in addition, decreased libido and impotence may occur.

Another 5-alpha reductase inhibitor is GlaxoSmithKline's dutasteride. This inhibits both type 1 and type 2 5-alpha-reductase enzymes (finasteride inhibits only type 2), giving a particularly marked suppression of DHT formation.

What's in the development pipeline?

Development of new alpha-adrenoceptor blockers continues. Silodosin from Kissei, which targets alpha receptors, is in Phase 2. In addition, GlaxoSmithKline is testing a fixed combination of dutasteride and an alpha-blocker (GI-198745) in Phase 3 trials and sanofi-aventis's alfuzosin aims to prevent acute urinary retention (a complication of benign prostatic hyperplasia that requires emergency treatment).

No new 5-alpha reductase inhibitors are currently in development, but a variety of other approaches is being tried. Vitamin D3 (calcitriol) 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; BioXell has a compound (BXL-628) in Phase 2 trial. Also at this stage, Eli Lilly and ICOS are studying tadalafil (Cialis). This compound may cause relaxation of the smooth muscle within an enlarged prostate, thereby easing urine flow.

Nymox Pharma also has a compound (NX-1207) in Phase 2 trial. Finally, some other hormonal approaches are being tried. Ardana Biosciences has a gonadotrophin releasing hormone antagonist (Teverelix) that reduces testosterone and dihydrotestosterone levels and has shown improvements in symptoms in a Phase 2 trial and Aeterna Zentaris has two Luteinizing Hormone Releasing Hormone antagonists in trial (Ozarelix, Phase 2, and Cetrorelix, Phase 3).

The longer-term future

Several effective medicines are now available for the treatment of the symptoms of benign prostatic hyperplasia and successful research continues into new approaches. Further research into the biology of the prostate and its growth regulation are also needed to further improve management of benign prostatic hyperplasia - a condition that is likely to become even more common with the 'greying' of Britain's population over the next two decades.

FOR FURTHER INFORMATION CONTACT:

The Prostate Research Campaign (UK)
10 Northfields Prospect, Putney Bridge Road
London, SW18 1PE
Phone: 020 8877 5840
Website: www.prostate-research.org.uk