Friday, June 13, 2008
Are Medications for the Treatment of Enlarged Prostate (Benign ...
Alpha adrenergic receptor blocker medications, including doxazosin (Cardura), prazosin (Minipress), alfuzosin (Uroxatral), and terazosin (Hytrin), cause a relaxation of prostate smooth muscle and increase urine flow (Lepor et al 1996; McConnell et al 2003). The FDA has approved all of these medications for the treatment of BPH, with the exception of Minipress. Minipress is a medication that has been on the market for the treatment of hypertension for many years; your doctor has the right to prescribe it for you "off label" for the treatment of BPH if he or she thinks it is indicated. There are no current plans to obtain an indication for Minipress for the treatment of BPH, since it has been off patent for many years. All of the alpha adrenergic receptor blocker medications have similar side effects including dizziness, postural hypotension, and fatigue. The potential benefit from relief of BPH symptoms is usually worth the side effects of these medications. However, Uroxatral should not be used in patients with liver problems and causes cardiac effects (lengthening of the Q-T interval).
Tamsulosin (Flomax) is a selective blocker of the ±-1A adrenergic receptor that has fewer side effects than the other alpha-blockers because it is more selective to the ±-1A adrenergic receptor than the other drugs reviewed above. The other alpha blockers block adrenergic receptors in both the heart and the brain as well as in the prostate. For this reason they can block the smooth muscles in the blood vessels in these areas and cause the blood vessels to dilate. This changes blood flow in the brain, with associated dizziness, fatigue, or the possibility of passing out if you stand up too quickly (postural hypotension). Since Flomax is more specific to the adrenergic receptors in the prostate, it has fewer of these side effects.
5±-reductase inhibitors include drugs like finasteride (Proscar). One of the most important factors contributing to BPH is the male hormone dihydrotestosterone (DHT). DHT normally stimulates prostate tissue in adolescent males, which leads to the ability to produce semen and therefore become fertile. In later age, however, DHT can stimulate prostate tissue in a counter-productive way. Proscar inhibits the enzyme responsible for the conversion of testosterone to DHT, 5±-reductase, thereby reducing DHT levels as much as 80%. This is associated with a decrease in prostate volume of 20%, since this hormone stimulates prostate tissue growth. Side effects include decreased libido, impotence and ejaculatory disorder. Dutasteride (Duagen) blocks both types 1 and 2 5±-reductase and has a similar side effect profile as finasteride.
In the PROscar Safety Plus Efficacy Canadian Two Year Study (PROSPECT), 613 men with moderate BPH symptoms were started on a two year treatment course with Proscar or placebo (Nickel et al 1996). Finasteride resulted in a statistically significant reduction in symptom scores compared to placebo, with a baseline score of 15.8 the difference between finasteride and placebo was only 0.4, not a very big difference. There was about a 10% increase in urinary flow rates. Over twice as many (15.8%) of finasteride patients developed impotence as patients on placebo (6.3%). In a study comparing finasteride to the alpha blocker terazosin and placebo, 1229 were randomized to blinded treatment for one year. Change in symptom scores were 2.6 for placebo, 3.2 for finasteride, 6.1 for terazosin, and 6.2 for terazosin and finasteride.(Lepor et al 1996) Similar improvements were seen with urine flow, with greater increases in urine flow for terazosin. Finasteride was no better than placebo, while terazosin was statistically significantly better than both finasteride and placebo. Impotence was higher with finasteride (9%) than placebo (5%) or terazosin (6%). Another study looking at the long term effects of these drugs studied 3047 patients for five years on placebo, doxazosin (alpha blocker), finasteride, or combination therapy. The outcome was a four point increase in BPH symptom score, urinary retention or incontinence. Doxazosin reduced progression by 39% and finasteride by 34% compared to placebo (both statistically significant) (McConnell et al 2003). Combination therapy was even better (66% reduction) and was associated with a reduction in the need for surgery, as was finasteride alone.
Based on these findings I recommend the use of the alpha blockers initially (doxazosin (Cardura), prazosin (Minipress), alfuzosin (Uroxatral), and terazosin (Hytrin) and Flomax) with addition of Proscar or Duagen depending on symptom response and side effects. Talk it over with your doctor.
Lepor H, Williford WO, Barry MJ (1996): The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group. New England Journal of Medicine 335:533-539.
McConnell JD, Roehrborn CG, Bautista OM (2003): The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. New England Journal of Medicine 349:2387-2398.
Nickel JC, Fradet Y, Boake RC, Pommerville PJ, Perreault JP, Afridi SK (1996): Efficacy and safety of finasteride therapy for benign prostatic hyperplasia: results of a 2-year randomized controlled trial (the PROSPECT study). PROscar Safety Plus Efficacy Canadian Two year Study. Canadian Medical Association Journal 348:602-606.
You can buy Proscar here
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