PDE-5 inhibitors, antimuscarinics may play role in BPH

August 15, 2006

In men with BPH, drugs indicated for other urologic conditions may play a role in the treatment of their lower urinary tract symptoms, suggest data from a number of studies presented at the 2006 AUA annual meeting. These studies were among those on BPH and LUTS highlighted by Claus G. Roehrborn, MD, professor and chairman of the department of urology at the University of Texas Southwestern Medical Center, Dallas.

Daily tadalafil (Cialis) can improve both BPH-related lower urinary tract symptoms as well as erectile dysfunction.

Phosphodiesterase type-5 (PDE-5) inhibitors-namely tadalafil, sildenafil citrate (Viagra), and vardenafil (Levitra)-are now the treatment of choice for most men with erectile dysfunction. Three different studies presented at this year's AUA meeting showed that the drugs also have an effect on urinary tract symptom severity and frequency in men with LUTS and BPH, but do not affect urinary flow rate.

Patients receiving tamsulosin (Flomax) combined with extended-release oxybutynin ER (Ditropan XL), an antimuscarinic agent, show a greater improvement in total and irritative International Prostate Symptoms Scores, as well as a greater improvement in quality-of-life score than do patients receiving tamsulosin plus placebo.

"This is an important step forward," Dr. Roehrborn said. "We have always treated LUTS as if it were only associated with BPH. We always knew but have not paid much attention to the observation that some men had less obstructive symptoms but more irritative symptoms. There is a growing understanding that these men may have overactive bladder."

Thus, some physicians are now considering the use of an alpha-blocker plus an antimuscarinic agent (eg, oxybutynin, darifenacin [Enablex], solifenacin [Vesicare], tolterodine tartrate [Detrol LA] trospium chloride [Sanctura]) for the treatment of irritative lower urinary tract symptoms in men.

Daily alfuzosin (Uroxatrol), 10 mg, reduces symptom progression and BPH-related events over 2 years. In men receiving alfuzosin, symptom score, bother, and flow improve, but the incidence of acute retention does not.

Dr. Roehrborn said the results of the 2-year alfuzosin study were similar to those of the landmark Medical Therapy for Prostatic Symptoms (MTOPS) study, which found that another alpha-blocker, doxazosin (Cardura), prevented symptomatic progression, but had no effect on the frequency of retention.

"This is a welcome study because it corroborates the MTOPS findings," he said. "It indicates that alpha-blockers treat the symptoms of BPH very well but do not prevent progression to retention, most likely because they do not interfere with the growth tendencies of the prostate."

The risk of iris prolapse during eye surgery is increased in men taking alpha-blockers for BPH, and the risk is highest with tamsulosin.

Iris prolapse, or floppy iris syndrome, is associated with a number of clinical presentations, diabetes being the most common. New data indicate that the use of alpha-blockers is also a risk factor for iris prolapse, although these effects should be completely reversible after stopping the alpha-blockers for 1 week, according to a paper published earlier this year (Naunyn Schmiedebergs Arch Pharmacol 2006; 372:346-53).

"This leads to the conclusion that it would be prudent for a physician to tell patients to stop taking alpha-blockers, perhaps a week prior to the cataract surgery," Dr. Roehrborn advised.

At a follow-up of up to 1 year, treatment with botulinum toxin type A (Botox) in men with BPH shows a substantial reduction in symptom score: from 18.7 to 9.0 points and from 19.3 to 8.3 points in men receiving 100 and 200 units, respectively.

Botulinum toxin is used to relax striated muscle for a number of clinical and cosmetic indications, but its use in men with BPH remains investigational.