BENIGN PROSTATIC HYPERTROPHY (BPH)

What is enlarged prostate?

Enlarged prostate, a condition known as benign prostatic hypertrophy (BPH) or benign prostatic hyperplasia, is very common. The prostate gland becomes enlarged in many men as they age. BPH rarely causes symptoms before age 40, but more than half of men in their 60s, and as many as 90 percent in their 70s and 80s, have some symptoms of BPH.

Treatment for an enlarged prostate is not always required and will importantly depend on whether there are accompanying urinary symptoms. Should treatment be necessary, Public Citizen advises using alpha-blockers, such as terazosin (HYTRIN) or doxazosin (CARDURA).

Many BPH symptoms result from the partial obstruction of the urethra, resulting in thickening of the bladder. This thickening causes the bladder to hold less urine, leading to frequent urination during the day and night. The gradual loss of bladder function may also result in incomplete emptying of the bladder. The symptoms of BPH vary, but the most common involve changes or problems with urination, such as:

• a hesitant, interrupted, weak stream
• urgency and leaking or dribbling
• more frequent urination, especially at night

The symptoms of BPH arise from both prostate enlargement leading to mechanical obstruction and increased tone of the smooth muscle in the prostate. The size of the prostate does not always determine how severe the obstruction or the symptoms will be. Some men with greatly enlarged glands have little obstruction and few symptoms, while others, whose glands are less enlarged, have more blockage and greater problems.

BPH treatment options

The alpha-blocker family, which acts to relax the smooth muscle of the prostate, includes five drugs: alfuzosin (UROXATRAL), doxazosin, prazosin (MINIPRESS), tamsulosin (FLOMAX) and terazosin. Alfuzosin and tamsulosin are FDA-approved to treat BPH. Terazosin and doxazosin are approved for both high blood pressure and enlarged prostate. Prazosin is not approved for the treatment of BPH but is approved to treat high blood pressure. We have listed alpha-blockers as “Do Not Use” drugs for the treatment of high blood pressure because they are less effective than other drugs at lowering high blood pressure.

The other type of drug for the treatment of BPH is the 5-ARI family, which acts to shrink the prostate. The first drug in this class, finasteride, was approved by the FDA in June 1992 as PROSCAR. Finasteride was also marketed in December 1997 as PROPECIA for hair regrowth. The second drug in this category, dutasteride, was approved in November 2001, but there is no study that compares dutasteride’s usefulness to that of finasteride, which is a last-choice drug for treating BPH (especially in light of the increased risk of serious prostate cancer).

Results from finasteride and terazosin trials

A large clinical trial published in 1996 compared the effect of the 5-ARI finasteride with the alpha-blocker terazosin in more than 1,000 men with BPH. This study lasted one year. Overall, it was found that terazosin was effective therapy, finasteride was not and the combination of terazosin and finasteride was not more effective than terazosin alone. However, the researchers did find that finasteride was effective in a group of men with very large glands, while terazosin was effective in men with very large or small prostate glands.

A different conclusion was reached in a clinical trial published in 2003 that involved more than 3,000 men and lasted four and a half years. This trial is known as the Medical Therapy of Prostatic Symptoms (MTOPS) study. It concluded that the combination of finasteride and terazosin was superior to either of the drugs used alone. There are several possible reasons for these divergent results. First, the MTOPS trial lasted much longer than the trial published in 1996 — 4 ½ versus one year. This is important because finasteride does not act rapidly and often requires six months to a year to work. Second, the two trials measured different outcomes. The 1996 trial measured symptom score and peak urinary flow rate, while the MTOPS trial measured clinical progression of BPH, described as the first occurrence of an increase over baseline of at least four points in the symptom score: acute urinary retention, kidney problems, recurrent urinary tract infection and urinary incontinence.

A possible association between finasteride use and male breast cancer was revealed in the MTOPS trial when four cases of breast cancer were reported in men taking finasteride. This rate is nearly 200 times greater than what is seen in men in the general population.

Finasteride has also been tested in a very large clinical trial called the Prostate Cancer Prevention Trial (PCPT), with mixed results. There was a 25 percent relative reduction (6 percent absolute reduction) in cancers in healthy men taking finasteride. This means that for every 17 men treated with finasteride for seven years, one cancer would be prevented. There was, however, a 1.7-fold increase in the risk of an aggressive tumor in those men who developed cancer.

We were opposed to the PCPT at its inception because of the theoretical harm that could come from giving healthy men finasteride. Now that the potential for harm is no longer theoretical, our advice is that finasteride should not be used for prostate cancer prevention. The findings of this trial are also applicable to the other drug in the class, dutasteride (AVODART).

What You Can Do

If your BPH symptoms are minimal, no treatment is necessary, no matter the size of your prostate gland. If you have BPH symptoms and do not have a very enlarged gland, then an alpha-blocker such as terazosin would be the best choice. If your prostate is very enlarged, treatment with an alpha-blocker would, again, be the best choice.

Do not use dutasteride or finasteride to relieve your symptoms. If you are taking one of these drugs, consult your health care provider about switching to one of the alpha-blocker drugs listed in the table.

Surgical procedures are also an option for men with severe symptomatic BPH.

Consumers may report serious adverse events or product quality problems to the FDA’s MedWatch Adverse Event Reporting program online or by regular mail, fax or phone.

• Online: www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
• Regular mail: Use postage-paid, pre-addressed FDA form 3500 and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
• Fax: (800) FDA-0178
• Phone: (800) FDA-1088

Safer Alternatives for the Treatment of Enlarged Prostate