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Special Health Reports


2012 Annual Report on Prostate Diseases

Covering advances in the diagnosis and treatment of prostate cancer, benign prostatic hyperplasia, erectile dysfunction, prostatitis, and related conditions

2. Prostate enlargement (benign prostatic hyperplasia)

Getting this "going" — and "growing" — problem under control

Around the time of a man's 25th birthday, his prostate begins to grow. This natural enlargement is called benign prostatic hyperplasia (BPH). It is the most common cause of prostate enlargement. Indeed, if a man lives long enough, he will almost certainly experience some degree of BPH — a benign condition that doesn't lead to cancer, although the two problems can coexist.

No one knows exactly why BPH occurs. One popular theory suggests that the prostate begins to grow because of shifts in the balance between testosterone, a male hormone, and estrogen, a female hormone present in men in small amounts. Testosterone production declines with advancing age, changing the ratio of testosterone to estrogen. Some animal studies have shown that this shift in hormone balance may start a chain reaction, causing the rapid cell multiplication seen with prostate enlargement. Other animal studies suggest that the accumulation of the male hormone dihydrotestosterone (DHT) in the prostate may encourage cells to divide.

Evidence suggesting a link between prostate enlargement and Western dietary patterns has also emerged. In 2002, researchers for the 51,529 men participating in the Health Professionals Follow-up Study reported that men with a higher intake of calories, protein, and some specific forms of polyunsaturated fats were more likely to develop an enlarged prostate than those who ate less of these nutrients. A 2007 analysis of the same participants showed that those who consumed the fewest vegetables had the highest risk of developing an enlarged prostate. A 2008 study of 4,770 participants in the Prostate Cancer Prevention Trial came to some similar conclusions: risk rose with a diet low in vegetables and high in total fat, polyunsaturated fat, and red meat. However, this study came to the opposite conclusion about protein, finding that it might actually reduce risk (see "Dietary factors and BPH"). These studies have also raised questions, because unsaturated fats are generally considered healthy, so it is not clear why they would raise risk of BPH.

Dietary factors and BPH

Kristal AR, Arnold KB, Schenk JM, et al. Dietary Patterns, Supplement Use, and the Risk of Symptomatic Benign Prostatic Hyperplasia: Results from the Prostate Cancer Prevention Trial. American Journal of Epidemiology 2008;167:925–34. PMID: 18263602.

Rohrmann S, Giovannucci E, Willett WC, Platz EA. Fruit and Vegetable Consumption, Intake of Micronutrients, and Benign Prostatic Hyperplasia in U.S. Men. American Journal of Clinical Nutrition 2007;85:523–29. PMID: 17284753.

Suzuki S, Platz EA, Kawachi I, et al. Intakes of Energy and Macronutrients and the Risk of Benign Prostatic Hyperplasia. American Journal of Clinical Nutrition 2002;75:689–97. PMID: 11916755.

Although 50% to 60% of men with BPH may never develop any symptoms, others find that BPH can make life miserable (see "Symptoms of BPH") and seek treatment. Interestingly, the size of the prostate does not always predict symptoms. Some men with large glands never have symptoms, while others with small glands do. When problems do occur, patients and their physicians have several medications from which to choose, so if one doesn't do the trick, another can be prescribed. And thanks to some refinements, surgical treatments are more effective and have fewer side effects than ever before.

Symptoms of BPH

The most common symptoms of BPH involve changes or problems with urination. These are sometimes referred to as lower urinary tract symptoms. They include

  • a hesitant, interrupted, or weak urine stream

  • urgency, leaking, or dribbling

  • a sense of incomplete emptying

  • more frequent urination, especially at night.

How BPH progresses

As the prostate enlarges, it starts to press against the urethra and the bladder (see Figure 4), like a foot stepping on a garden hose or fingers pinching a soda straw. This gradually obstructs the flow of urine, forcing the bladder to work harder to push urine through the urethra. But straining to urinate, although unavoidable, only makes matters worse. Like any muscle, the bladder wall becomes thicker with work. This reduces the amount of urine the bladder can hold and causes it to contract even when it contains only small amounts of urine, causing more frequent urination. Eventually, the bladder becomes so thick that it loses its elasticity and can no longer empty itself.

Figure 4: An inside look at BPH

An inside look at BPH

As the prostate gland enlarges, it constricts the urethra, the tube that carries urine out of the body, impeding urine flow. The bladder has to work harder to force stored urine out. Over time, the bladder walls thicken, leaving less and less room for urine.

The narrowing of the urethra and partial emptying of the bladder cause many of the problems of BPH. You may feel as though you have to urinate immediately, yet have to strain to do so. You may have a weak urinary stream or one that stops and starts. You may dribble after urinating or feel as if you're not emptying your bladder completely. And you may feel the need to urinate frequently — even every few minutes — causing many awakenings during the night. Some men also experience urinary incontinence, the involuntary discharge of urine.

The course of BPH varies from one man to the next. In some, the disease may progress to a certain point and reach a plateau of mild symptoms that never worsen, or the prostate may continue to enlarge but grow away from the urethra, causing no additional impingement. Particularly in the early years of the condition, the symptoms may abate before worsening again. In other men, the disease progresses and the symptoms intensify steadily, year after year. In the worst cases, the prostate can grow as large as an orange.

Most physicians advise against medical or surgical treatment for men with mild symptoms, because the side effects of the treatment outweigh the potential benefits. But if the symptoms worsen, ordinary activities may become a challenge. A 65-year-old man may find it hard to sit through a lengthy meeting without having to excuse himself to use the bathroom. He may need to request an aisle seat at the theater or a sports event, so he can rush to the bathroom at any time. If he has a problem with leakage, he may begin wearing dark clothing to conceal his incontinence. And he may feel fatigued during the day because of frequent nighttime awakenings.

BPH can also produce complications that, while not life-threatening, nonetheless require medical attention. If the blockage is so severe that it keeps your bladder from emptying completely, you may be vulnerable to frequent urinary tract infections. The risk of developing bladder stones also increases. The growth of the prostate can rupture blood vessels in the urethra, causing blood to appear in the urine. If obstructive BPH goes untreated for too long, the bladder may become distended, its muscular wall may weaken, and you may be unable to squeeze any urine past the obstructing prostate gland, a condition known as acute urinary retention. The bladder may become so distended that urine cannot adequately empty from the kidneys. In the most severe cases, this can lead to kidney failure. And not being able to urinate at all is a medical emergency, requiring the temporary passage of a catheter (a thin tube) through the urethra to allow the bladder to drain. Fortunately, such complications are uncommon because most men seek medical attention well before serious problems develop.

Getting help

If you experience the symptoms of BPH, see your doctor. During an initial evaluation, the doctor will take a medical history. Expect questions about your urinary flow problems, how long the symptoms have been present, and any prior genitourinary surgery or procedures. Most likely, he or she will ask about your health habits and any medications that may have made the symptoms worse. Your doctor may also ask you to complete a questionnaire, such as the American Urological Association Urinary Symptom Score, to help evaluate the severity of your BPH (see "Your urinary symptom score").

An adequate physical exam and diagnostic workup includes a digital rectal examination (DRE) and, if you and your doctor concur, a prostate-specific antigen (PSA) test. It also includes several other laboratory tests, such as a urinalysis. This allows your doctor to rule out bacterial infections and look for untreated diabetes, which can produce frequent urination, particularly at night.

In a sense, your lifestyle will determine how burdensome you find BPH. The symptoms that disrupt the day-to-day activities of one man may have less of an effect on another who perhaps spends much of his day at home. Work with your physician to determine what, if any, treatment is the best choice.

Your urinary symptom score

To evaluate the severity of your benign prostatic hyperplasia (BPH) and determine what treatment, if any, might be best for you, your doctor may ask you to complete a questionnaire like the one below. Circle one number to respond to each question, and then calculate the total score.

In general, if your symptoms are mild (scores of 1–7), no treatment is needed. If your symptoms are moderate (scores of 8–19), you probably need some form of treatment, such as medication. If your symptoms are severe (scores of 20 or greater), surgery is likely to be your best treatment option.

1. Over the past month, how often have you had a sensation of not having emptied your bladder completely after you finished urinating?

0 ____ Not at all
1 ____ Less than 1 in 5 times
2 ____ Less than half the time
3 ____ About half the time
4 ____ More than half the time
5 ____ Almost always

2. Over the past month, how often have you had to urinate again less than two hours after you last finished urinating?

0 ____ Not at all
1 ____ Less than 1 in 5 times
2 ____ Less than half the time
3 ____ About half the time
4 ____ More than half the time
5 ____ Almost always

3. Over the past month, how often have you stopped and started again several times while urinating?

0 ____ Not at all
1 ____ Less than 1 in 5 times
2 ____ Less than half the time
3 ____ About half the time
4 ____ More than half the time
5 ____ Almost always

4. Over the past month, how often have you found it difficult to postpone urination?

0 ____ Not at all
1 ____ Less than 1 in 5 times
2 ____ Less than half the time
3 ____ About half the time
4 ____ More than half the time
5 ____ Almost always

5. Over the past month, how often have you had a weak urinary stream?

0 ____ Not at all
1 ____ Less than 1 in 5 times
2 ____ Less than half the time
3 ____ About half the time
4 ____ More than half the time
5 ____ Almost always

6. Over the past month, how often have you had to push or strain to begin urination?

0 ____ Not at all
1 ____ Less than 1 in 5 times
2 ____ Less than half the time
3 ____ About half the time
4 ____ More than half the time
5 ____ Almost always

7. Over the past month, how many times, typically, did you get up to urinate between the time you went to bed at night and the time you got up in the morning?

0 ____ None
1 ____ Once
2 ____ Twice
3 ____ Three times
4 ____ Four times
5 ____ Five times or more

8. How would you feel if you had to live with your urinary condition the way it is now, no better, no worse, for the rest of your life?

0 ____ Delighted
1 ____ Pleased
2 ____ Mostly satisfied
3 ____ Mixed
4 ____ Mostly not satisfied
5 ____ Unhappy

Total score: ____

Source: American Urological Association

Treating BPH

When symptoms are not particularly bothersome, you and your doctor may choose to do nothing other than watchful waiting, which involves regular monitoring to make sure you aren't developing any complications, but no treatment. For more troubling symptoms, most doctors begin by recommending a combination of lifestyle changes (see "Tips for relieving BPH symptoms") and medication. Often this will be enough to relieve the worst symptoms and allow you to avoid surgery. Another option is learning intermittent self-catheterization (see Figure 6).

Tips for relieving BPH symptoms

These simple steps can help relieve some of the symptoms of BPH:

  • Reduce stress by exercising regularly and practicing relaxation techniques such as meditation. Some men who are nervous and tense urinate more frequently.

  • When you go to the bathroom, take the time to empty your bladder completely. This will reduce the need for subsequent trips to the toilet.

  • Talk with your doctor about all prescription and over-the-counter medications you take; some, such as antihistamines and decongestants, may affect urination. Your doctor may be able to adjust dosages or change your schedule for taking these drugs, or he or she may prescribe different medications that cause fewer urinary problems.

  • Avoid drinking fluids in the evening, particularly caffeinated and alcoholic beverages. Both can affect the muscle tone of the bladder, and both stimulate the kidneys to produce urine, leading to nighttime urination.

Should surgery become necessary, keep in mind that there are several surgical techniques available and that just because a technique is new doesn't mean it is better. Before proceeding, check with your health insurance company to make sure your choice is covered. Not every health plan covers every procedure, and because there are several effective treatments, you may want to choose one that your insurance will cover. Also, if you choose a surgical procedure, find a surgeon who has extensive experience with that specific procedure.

Table 2: Medications for BPH

Medication

Potential side effects

Comments

5-alpha-reductase inhibitors

dutasteride (Avodart)

finasteride (Proscar, generic)

Although uncommon, decreased libido, decreased ejaculate volume, and impotence may occur.

Help shrink larger prostate glands. Reduce need for surgery. Not beneficial for small prostates. Slow to act; can take up to two years to see full benefits. Can lower PSA levels considerably.

May increase risk of aggressive prostate cancer; important to monitor PSA.

Alpha blockers (nonselective)

doxazosin (Cardura, generic)

terazosin (Hytrin, generic)

Dizziness, headache, and fatigue are most common. Nasal congestion, dry mouth, and swelling in the ankles can also occur. Hypotension (low blood pressure), although rare, may pose a danger for some people.

Should be used carefully by those with hypertension or heart disease.

Alpha blockers (selective)

alfuzosin (Uroxatral)

silodosin (Rapaflo)

tamsulosin (Flomax, generic)

Dizziness, headache, and fatigue are most common. Nasal congestion, dry mouth, and swelling in the ankles can also occur.

Do not lower blood pressure, but men taking silodosin may notice a drop in blood pressure upon standing.

Combination

dutasteride and tamsulosin (Jalyn)

Dizziness, headache, and fatigue may occur. Hypotension (low blood pressure), although rare, may pose a danger for some people.

Can lower PSA levels considerably.

May increase risk of aggressive prostate cancer; important to monitor PSA.

PDE5 inhibitor

tadalafil (Cialis)

Headache, flushing, upset stomach, nasal congestion. Temporary disturbances in color vision possible. In rare cases, may cause priapism, an erection that lasts too long.

Do not take more than one pill in 24 hours. Do not take if you are also taking alpha blockers or nitrate medications, to avoid risk of hypotension (low blood pressure that can cause fainting).

Medications that treat BPH

Before suggesting surgery, your doctor is likely to recommend medication for BPH (see Table 2). The FDA has approved three types of drugs for BPH:

  • 5-alpha-reductase inhibitors, including dutasteride (Avodart) and finasteride (Proscar, generic)

  • alpha blockers, including doxazosin (Cardura, generic), terazosin (Hytrin, generic), alfuzosin (Uroxatral), silodosin (Rapaflo), and tamsulosin (Flomax, generic)

  • a PDE5 inhibitor, tadalafil (Cialis).

The FDA has also approved a medication that combines the 5-alpha-reductase inhibitor dutasteride with the alpha blocker tamsulosin (the combination is marketed as Jalyn). These drugs work in different ways to alleviate urinary symptoms, and they often work well together (see Figure 5).

Figure 5: How BPH medications can help

image

Alpha blockers attach to certain receptors in the prostate, bladder, and urethra, blocking chemical signals that tell muscles in these structures to contract. As a result, the muscles relax, allowing urine to flow more freely.

image

The 5-alpha-reductase inhibitors block the hormone responsible for prostate growth, eventually causing the prostate to shrink.

Alpha blockers, for example, deal with the "going" problem by relaxing certain muscles in the prostate and urinary tract. The 5-alpha-reductase inhibitors deal with the "growing" problem by reducing the size of the prostate. The 5-alpha-reductase inhibitors act slowly, taking a few months to have an effect. Indeed, you may not see the maximum benefit until you've been taking the medication for six months to a year. These drugs work best for men with large prostates. (Your doctor can give you a rough estimate of the size of your prostate by doing a DRE.) Alpha blockers, at least in some men, reduce symptoms much more quickly. In general, alpha blockers are better at relieving urinary symptoms such as difficult or frequent urination. But 5-alpha-reductase inhibitors have a stronger track record for reducing the chance that you'll need surgery or will experience complications, such as acute urinary retention, that occur when the prostate gland is large. With this in mind, some doctors prescribe both kinds of drugs for men with large prostates.

It's not clear why PDE5 inhibitors, normally used to treat erectile dysfunction, help improve BPH symptoms. But after several studies suggested that men taking these erection drugs also found their urinary difficulties subsided, investigators decided to conduct separate studies involving only men with BPH. Two studies concluded that the PDE5 inhibitor tadalafil improved BPH symptoms, and one concluded that it improved both BPH symptoms and erectile function (for more information, see "PDE5 inhibitors").

You generally need to take BPH drugs indefinitely to maintain their benefits. If you stop taking the medication, the symptoms usually return to their previous levels. Over all, compared with surgical procedures, medication has a lower risk for serious adverse effects, leading most men to choose drug therapy as their initial treatment.

Figure 6: Intermittent self-catheterization for urinary retention

One of the reasons that men who have BPH have to urinate so frequently is that they are unable to completely empty their bladder — a problem known as urinary retention. This is a common complication of BPH. The amount of urine left in the bladder is known as the post-void residual. When the bladder does not empty on a regular basis, a man may feel a constant sense of fullness in his abdomen and a nagging need to urinate, yet when the time comes his urine stream may be weak or intermittent.

Urinary retention is more than an annoyance. A man with significant post-void residual risks urinary tract infections and other medical complications. Incomplete voiding can also affect a man's quality of life. Men sit on their prostates. Sitting for prolonged periods — such as during business meetings or on airplanes — places extra pressure not only on the prostate but on the bladder, and that can increase the need to urinate. If a man's bladder is already partly full because of urinary retention, the pressure can become unbearable. Frequent fliers with this problem know the agony of waiting for the seatbelt light to go off so they can reach a bathroom.

If urinary retention is a problem for you, one option that may help is chronic intermittent catheterization. Men who learn this technique can more completely empty their bladder by using a home catheter that is smaller and more portable than the Foley catheters used in medical procedures. Using this technique along with some common-sense additional strategies — such as not drinking a lot of water, alcohol, or caffeinated beverages (all increase urination) — may help you get through the next long plane trip or meeting. Here's how to practice chronic intermittent catheterization:

  1. Find a clean and private environment, preferably with counter or desk space to use as necessary, where you can remain uninterrupted for a few minutes. You'll need a catheter (your doctor can provide you with one) and a toilet or container to drain urine into.

  2. If a sink is available, wash your hands with soap and water, and clean the tip of your penis, including the opening to the urethra. (You can use disposable towelettes if you prefer.)

  3. Lubricate the catheter using a water-based lubricant such as K-Y jelly. Do not use a petroleum-based lubricant such as Vaseline.

  4. Get into a comfortable position. Some men prefer to catheterize themselves standing up, while others prefer to be seated or propped up in a bed.

  5. Grasp your penis just below the head and pull it out and slightly upward to straighten the urethra.

  6. If you are not circumcised, retract the foreskin. Gently insert the catheter into the opening of the urethra and slide it slowly inward, toward your belly. The lubricated catheter should slide easily through the urethra (A).

image

  1. You may notice some resistance once you reach the level of the prostate (especially if tissue is pressing against the walls of the urethra) and at the sphincter located at the entrance of the bladder. If so, breathe deeply or practice another relaxation technique so that you can continue gently advancing the catheter.

  2. Continue advancing the catheter until urine starts to flow downward into the toilet bowl or other container. This is a sign that the catheter has entered the bladder (B).

image

  1. Advance the catheter another inch and then hold it in place until the urine stops flowing. At that point, the bladder is empty.

  2. Slowly withdraw the catheter.

  3. Discard a disposable catheter immediately. If the catheter is reusable, wash it completely, dry it, and store it in a clean container. Even a secure plastic bag is sufficient. Check with your health provider about how often a reusable catheter can be used.

  4. Keep extra catheters on hand for use as needed.

Alpha blockers. For men with moderate enlargement of the prostate and moderate urinary problems that are too bothersome to simply do nothing, doctors often first prescribe an alpha blocker. Originally approved to treat high blood pressure, alpha blockers relieve urinary symptoms by relaxing the smooth muscle tissue in the prostate and the surrounding capsule. This relieves constriction of the urethra and allows urine to flow more easily.

Alpha blockers come in two forms: selective and nonselective. Because nonselective alpha blockers can lower blood pressure, they aren't the right choice for every man. Some doctors are hesitant to prescribe nonselective alpha blockers for men who are already on another blood pressure medication. Taking several antihypertensive drugs at once can cause an excessive drop in blood pressure, producing faintness or dizziness, especially when getting up from a chair or out of bed. Sudden episodes of low blood pressure can be dangerous for men with vascular disease, which places them at high risk for a heart attack or stroke. However, the selective alpha blockers are more specific to the prostate and don't lower blood pressure, making them useful for men who don't need or couldn't tolerate this additional effect.

In addition, some men on alpha blockers experience dizziness, lack of energy, swelling of the ankles, or retrograde ejaculation, which occurs when semen flows back into the bladder rather than out through the penis upon orgasm. You may need to make several visits to your doctor and try several prescriptions to arrive at the appropriate medication and the right dose.

5-alpha-reductase inhibitors. These medications help shrink the prostate, but they work slowly and may be less effective at relieving symptoms than the alpha blockers. Finasteride and dutasteride shrink the prostate by changing its hormone balance. Specifically, they reduce levels of the male hormone dihydrotestosterone (DHT), which plays a role in prostate growth. The drugs interfere with the action of 5-alpha reductase, an enzyme that converts testosterone to DHT. Interestingly, their ability to lower DHT levels also makes these drugs useful in treating hair loss in men.

A 1996 analysis of six studies comparing finasteride against a placebo found that the medication works somewhat better in men with large prostates, and that it may not be a good choice for those with smaller glands. Further news came in 1998 from a study involving 3,040 men, which showed that for men with symptoms of urinary obstruction and prostatic enlargement, finasteride provided significant benefits. Patients who took it for four years experienced fewer symptoms, a reduction in prostate size, an increase in urinary flow rate, and less likelihood of needing surgery or experiencing acute urinary retention. A year later, researchers reported that finasteride was most effective in men with large prostates and with PSA levels of 1.4 nanograms per milliliter (ng/ml) or higher. (To read these studies on your own, see "5-alpha-reductase inhibitors for BPH.")

5-alpha-reductase inhibitors for BPH

Boyle P, Gould AL, Roehrborn CG. Prostate Volume Predicts Outcome of Treatment of Benign Prostatic Hyperplasia with Finasteride: Meta-Analysis of Randomized Clinical Trials. Urology 1996;48:398–405. PMID: 8804493.

McConnell JD, Bruskewitz R, Walsh P, et al. The Effect of Finasteride on the Risk of Acute Urinary Retention and the Need for Surgical Treatment Among Men with Benign Prostatic Hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group. New England Journal of Medicine 1998;338:557–63. PMID: 9475762.

Roehrborn CG, Boyle P, Bergner D, et al. Serum Prostate-Specific Antigen and Prostate Volume Predict Long-Term Changes in Symptoms and Flow Rate: Results of a Four-Year, Randomized Trial Comparing Finasteride Versus Placebo. Urology 1999;54:662–69. PMID: 10510925.

These medications tend to reduce PSA levels by about 50%, although the actual reduction varies. Most physicians advise obtaining a baseline PSA value before beginning treatment with a 5-alpha-reductase inhibitor, and then having another after six months to a year to see how much PSA was affected. If the PSA does not go down by 50%, or if it begins to rise after a man starts taking the drug, a biopsy may be necessary to determine if this is a sign of cancer. (See "Physician interview: Keeping the FDA ruling on 5-alpha-reductase inhibitors in perspective.")

Finasteride and dutasteride can interfere with sexual function, although this effect is relatively uncommon. According to one clinical trial, as the drug shrinks the prostate gland, some sexually active men (8.1%) have difficulty achieving erections, and others (6.4%) experience a decline in sexual desire. A few (3.7%) notice a decrease in the volume of their ejaculate, which some may find troublesome. In clinical practice, however, doctors say these side effects are much more common, affecting up to a third of patients (see "Why the discrepancy?").

Why the discrepancy?

The rate of side effects reported in clinical trials is often different from that seen in clinical practice. Researchers may not ask about particular side effects, so unless participants in a clinical trial know to report them, that information won't be recorded. (This underscores the need for consistent questioning of trial participants during clinical studies.) Also, a doctor may have a closer relationship with a patient than a researcher and may be more inclined to ask about side effects and how bothersome they are.

Combination therapy. Because alpha blockers and 5-alpha-reductase inhibitors work differently, researchers have hypothesized that taking both types of medication might be more effective for controlling symptoms than taking just one. After several studies confirmed this, the FDA in 2010 approved a pill — marketed as Jalyn — that combines the 5-alpha-reductase inhibitor dutasteride with the alpha blocker tamsulosin.

PDE5 inhibitors. Studies have established a physiological link between erectile dysfunction and the urinary symptoms that accompany BPH. Prescribed for erectile dysfunction, phosphodiesterase-5 (PDE5) inhibitors augment cyclic GMP, a chemical that relaxes smooth muscle in the penis, improving blood flow during sexual stimulation. PDE5 inhibitors — sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) — also seem to relax smooth muscle in the bladder neck, urethra, and prostate. A handful of clinical trials have shown that these drugs improve both erectile function and urinary symptoms in men with both conditions.

Based on three studies that specifically evaluated the use of PDE5 inhibitors for BPH, in 2011 the FDA approved tadalafil (Cialis) as a stand-alone treatment for BPH-related urinary symptoms and as a dual treatment to address both BPH and erectile dysfunction. Participants took 5 mg of tadalafil a day — at the lower end of the dosing scale when this pill is prescribed for erectile dysfunction. In all three studies, daily tadalafil significantly improved BPH symptoms as assessed through patient questionnaires that asked about issues such as urinary urgency and frequency (see "Evidence supporting tadalafil for BPH").

Evidence supporting tadalafil for BPH

Donatucci CF, Brock GB, Goldfischer ER, et al. Tadalafil Administered Once Daily for Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: A 1-Year, Open-Label Extension Study. BJU International 2011;107:1110–16. PMID: 21244606.

Egerdie RB, Auerbach S, Roehrborn CG, et al. Tadalafil 2.5 or 5 mg Administered Once Daily for 12 Weeks in Men with Both Erectile Dysfunction and Signs and Symptoms of Benign Prostatic Hyperplasia: Results of a Randomized, Placebo-Controlled, Double-Blind Study. Journal of Sexual Medicine 2011; Electronic publication ahead of print. PMID: 21981682.

Porst H, Kim ED, Casabe AR, et al. Efficacy and Safety of Tadalafil Once Daily in the Treatment of Men With Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia: Results of an International Randomized, Double-Blind, Placebo-Controlled Trial. European Urology 2011;60:1105–13. PMID: 21871706.

Although the fact that an erectile dysfunction drug can also perform "double duty" to relieve BPH may be welcome news to some men, it's also wise to understand the limitations. Most studies examining the use of PDE5 inhibitors have been relatively short — 12 weeks — meaning that researchers have little data on whether they affect the progression of BPH or instead only delay more aggressive treatments. One of the studies involving tadalafil lasted one year, but there are no longer-term data on the safety of this or other PDE5 inhibitors.

The FDA advises men against taking tadalafil with nitrates (such as nitroglycerin), because combining these two drugs may cause a risky drop in blood pressure. Traditionally doctors also advised that tadalafil and other PDE5 inhibitors not be combined with alpha blockers to treat BPH, out of concern that the combination might also dangerously reduce blood pressure. However, the drugs are often used together and in most cases do not cause problems. To be safe, start at the lowest dose possible and try to take the drugs at different times of the day.

Cancer warning

In addition to treating BPH, the 5-alpha-reductase inhibitors were also tested as a means of preventing prostate cancer. Instead, the FDA concluded that these drugs actually cause a small increase in risk for developing aggressive prostate cancer. If you are taking a 5-alpha-reductase inhibitor for BPH, or taking the combination pill Jalyn (which contains one of these drugs), read the advice from Editor in Chief Marc Garnick in "Physician interview: Keeping the FDA ruling on 5-alpha-reductase inhibitors in perspective."

Herbal remedies

A variety of herbal remedies are marketed as BPH remedies, but so far evidence for their effectiveness remains limited. In addition, standardized doses and preparations have not been determined.

Saw palmetto. One herbal remedy often touted for the treatment of the urinary effects of BPH is saw palmetto, which is made with extracts of the fruit of the saw palmetto plant. The active ingredients are thought to be the various sterols, or hormone-like substances, in the plant extract. American Indians have long used saw palmetto as a diuretic. But while early studies of various saw palmetto products concluded that the supplements moderately improve urinary tract symptoms and urine flow, more recent — and better designed — studies have concluded otherwise.

A federally funded study published in 2011, for example, concluded that saw palmetto — even at high doses — was no more effective at relieving BPH than placebo. The multisite study included nearly 370 men older than 45 who had moderate symptoms of BPH. Over 72 weeks, the participants took a daily dose of either saw palmetto or placebo. As the study progressed, the standard dose of 320 mg/day of saw palmetto was tripled. Despite the increase in dose, however, at the end of the study saw palmetto did not work any better than placebo.

These findings were consistent with the results of a 2006 study that found saw palmetto to be no better than placebo: there was no significant difference between the men who took saw palmetto and those who didn't on such measures as prostate size, PSA level, or maximum urine flow.

In addition to its lack of effectiveness, another drawback of this herbal supplement, as with most nonprescription herbal products, is that its composition and dosage have not been standardized, and the FDA doesn't regulate it. If you decide to use saw palmetto in spite of the negative research, tell your doctor so he or she will be alert to possible interactions between it and any other medications you take.

Pygeum africanum. This extract of an African prune tree is sometimes used as a treatment for urinary symptoms. While this substance may modestly improve urologic symptoms and flow, it's not clear how effective it is compared with standard medical interventions, such as alpha blockers or 5-alpha-reductase inhibitors. Nor is there information about whether it prevents long-term complications of BPH, such as acute urinary retention.

Beta sitosterols. Preparations containing beta sitosterols — derived from the South African star grass — are sometimes used to treat symptoms of BPH. These substances may improve urinary flow and other BPH symptoms, but their long-term effectiveness, safety, and ability to prevent BPH complications are unknown.

To read the studies on herbal remedies, see "Research on herbal remedies."

Research on herbal remedies

Barry MJ, Meleth S, Lee JY, et al. Effect of Increasing Doses of Saw Palmetto Extract on Lower Urinary Tract Symptoms: A Randomized Trial. Journal of the American Medical Association 2011;306:1344–51. PMID: 21954478.

Bent S, Kane C, Shinohara K, et al. Saw Palmetto for Benign Prostatic Hyperplasia. New England Journal of Medicine 2006;354:557–66. PMID: 16467543.

Tacklind J, MacDonald R, Rutks I, Wilt TJ. Serenoa Repens for Benign Prostatic Hyperplasia. Cochrane Database of Systematic Reviews 2009;(2):CD001423. PMID: 19370565.

Wilt TJ, Ishani A, Stark G, et al. Saw Palmetto Extracts for Treatment of Benign Prostatic Hyperplasia: A Systematic Review. Journal of the American Medical Association 1998;280:1604–609. PMID: 9820264.

Wilt TJ, Ishani A, MacDonald R, et al. Pygeum Africanum for Benign Prostatic Hyperplasia. Cochrane Database of Systematic Reviews 2002;(1):CD001044. PMID: 11869585.

Wilt TJ, Ishani A, MacDonald R, et al. Beta-Sitosterols for Benign Prostatic Hyperplasia. Cochrane Database of Systematic Reviews 2000;(2):CD001043. PMID: 10796740.

Surgical options

If the results of watchful waiting and medication or other therapies are not satisfactory, you and your doctor will need to determine whether surgery or another procedure may be right for you. In the past, if BPH symptoms were severe — or if they were modest but still disrupted a patient's life — doctors almost universally recommended a surgical procedure called transurethral resection of the prostate (TURP). Although TURP is still widely used and is considered the gold standard by many doctors, alternatives are available. Explanations of the most common procedures are below; for a comparison of procedures, see Table 3.

Transurethral resection of the prostate (TURP). TURP, often inelegantly referred to as the "roto-rooter" technique, is an incision-free surgical procedure that cuts away excess prostate tissue with an electrical loop. TURP remains the most common form of prostate surgery and is usually more successful than medication. It relieves urinary obstruction in at least 85% to 90% of men, and the improvement is usually long-lasting. However, urinary problems can recur if the prostate tissue grows back. Not surprisingly, the younger you are, the more likely it is that you'll eventually need another treatment.

The hour-long procedure takes place in an operating room under general or spinal anesthesia, given just before the operation begins. Typically, you will have an enema the preceding night and will be told not to eat or drink for eight hours before the anesthesia. During the procedure, the surgeon uses an instrument called a resectoscope to view the prostate (see Figure 7). The surgeon threads the resectoscope through the penis to the prostate, then uses the electrical loop to cut away the overgrown tissue that's pressing against the urethra. You may spend one to two days recovering in the hospital. While recovering, you urinate through a thin tube, or catheter, inserted into the bladder through the penis. Once home, you may have to restrict heavy physical activity for two weeks or more to prevent bleeding.

Figure 7: Transurethral resection of the prostate (TURP)

image

During transurethral resection of the prostate (TURP), the surgeon inserts a thin tube called a resectoscope into the urethra and threads it up into the enlarged prostate (A). The resectoscope contains a tiny camera allowing the surgeon to view the gland throughout the operation, as well as an electrical loop. The surgeon uses the loop to chip away at overgrown prostate tissue blocking the urethra (B). After the procedure, the enlarged passageway allows urine to flow more easily (C).

Most men who've had TURP experience retrograde ejaculation during sexual activity — that is, the semen does not come out of the penis, but instead flows backward into the bladder. This occurs because the surgery destroys the valve that would ordinarily prevent this from happening. The semen is later flushed out with the urine. While not harmful to your health, retrograde ejaculation does make it more difficult to father children, a factor that you must weigh when considering TURP if you have not yet completed your family.

The more worrisome complications of TURP occur in about 5% to 10% of patients. These include blood loss, impotence, urinary incontinence, infections, and complications related to the anesthesia. The risk of complications needs to be considered when choosing treatment options, but TURP remains the gold standard of treatment for BPH. Interestingly, a study of U.S. veterans has suggested that TURP is no more likely to cause sexual problems or incontinence than watchful waiting.

About 2% of men who have the procedure develop TURP syndrome, which causes symptoms such as confusion, nausea, vomiting, high blood pressure, and visual distortions. The syndrome develops as a complication of the fluid used to keep the surgical area clean during TURP. Such "irrigation fluids" are used in all sorts of surgery, but the solution used depends on the procedure. Traditionally, the irrigation fluids used most often during TURP are glycine or a combination of sorbitol and mannitol. Although generally safe, in some men these solutions can promote fluid buildup. There is also some evidence that at high levels glycine may be toxic to the liver, kidneys, and pancreas.

A safer alternative is saline solution — used in many other types of operations — but until recently this solution could not be used in TURP because saline conducts electricity and can interfere with the electrical charge delivered by a traditional resectoscope. A new type of resectoscope, using a different type of electrical grounding device, is designed to work with saline solution. Known as a coaxial continuous-flow bipolar resectoscope, the device is more expensive than traditional resectoscopes but may offer an alternative to men at risk for TURP syndrome, or who have had it in the past. (For a patient's perspective on this new variation on TURP, see "A patient's perspective: Bipolar transurethral resection of the prostate (TURP).")

On rare occasions, TURP isn't a good option because the prostate has grown too large. Instead, open prostatectomy is necessary. In this procedure, the surgeon removes tissue blocking the urethra through an incision in the lower abdomen, leaving the rest of the prostate gland in place. Generally, this operation requires a longer hospital stay. On the other hand, compared with TURP, it reduces the likelihood that the tissues will grow back or that problems will recur.

A patient's perspective: Bipolar transurethral resection of the prostate (TURP)

Robert Bach kept a diary recording his experience with an innovative TURP procedure. Here's what he had to say.

I'm 71 years old. About five years ago, I developed recurrent urinary tract infections. My ability to urinate was compromised. I went to a urologist, who diagnosed benign prostatic hyperplasia (BPH). I started taking Flomax, and continued for several years.

In January 2009 I consulted with a urologist at my local hospital and, because recurrent prostatitis and BPH caused poor drainage of my bladder, I decided to switch to Uroxatral in place of Flomax and to start taking Proscar to shrink the prostate gland and improve flow from the bladder.

The following June, I consulted with Dr. Marc Garnick at Beth Israel Deaconess Medical Center (BIDMC)* because of continuing symptoms of poor bladder drainage. Dr. Garnick performed a full physical exam, including a DRE. He ordered some blood tests, including a PSA, to rule out prostate cancer.

On June 30, my PSA was 3.14. Because the DRE might have caused my PSA to rise, the test was repeated on July 6, and produced a value of 1.78. I consulted with Dr. William DeWolf, a surgeon at BIDMC,** later that month, and he performed a saturation prostate biopsy of 20 samples on August 5, all of which showed no prostate cancer or precancer cells present.***

By this point, the Proscar appeared to be working, as my urine flow improved and my BPH symptoms receded. My condition remained stable for most of 2010, but toward the end of the year, in December, some bladder (and possibly prostate) irritation returned and continued into January 2011.

In February, after a brief vacation in Florida, I returned with a severe flu and developed pneumonia. I started treating the flu with one antibiotic (azithromycin or "Z-pack") and later the pneumonia with another (Levaquin). While taking the drugs my prostatitis symptoms improved, which led me to believe that I may have had a low-grade infection of the prostate or bladder.

In March and April my symptoms of irritation returned and I consulted my local urologist. He performed urine analysis, urine cytology, ultrasound of my kidneys, and cystoscopy to examine the bladder. Urine cytology showed some cells that were not cancerous, and the other two tests were negative — meaning nothing was wrong. He prescribed a medication for bladder irritation. I continued to have symptoms of irritation of the bladder/prostate during a 10-day trip in April, and on May 5, I had a blood test to check cholesterol, thyroid, and liver functions. Included in that test was a PSA, which I had not been testing since my negative prostate biopsy in August 2009. The PSA test produced a 2.99 value.

On July 14, I consulted Dr. DeWolf about my continuing bladder and prostate irritation and the high PSA value. We discussed my having a TURP to promote drainage of the bladder and reduce irritation. At the age of 71, I felt strongly that now was the time to have the procedure. I am no longer sexually active, but in prior years when I was taking Uroxatral, I experienced reduced ejaculation, retrograde ejaculation, and reduced sexual pleasure from ejaculation. I would expect this state to continue after TURP. At my age, I decided I would choose to void well over having the additional sensation of normal ejaculation.

We scheduled a flow dynamics test for October 7. The test demonstrated normal functioning of the bladder, but retention of about 200 ml of urine, all indicative of the benefit that would accrue from a TURP.**** We scheduled a TURP procedure for November 4. I decided that I wanted to do this once, and the TURP offered a lifetime fix.

On October 11, I reviewed the procedure to be performed with Dr. DeWolf and had a pre-op meeting with the Anesthesiology Department at BIDMC. What follows are some notes I made about what the procedure felt like and how my recovery progressed.

Editor's notes:

*Dr. Garnick is also the editor in chief of Harvard's 2012 Annual Report on Prostate Diseases.

**Dr. DeWolf is also on the editorial board of Harvard's 2012 Annual Report on Prostate Diseases.

***A DRE revealed that Bach's gland was asymmetrical and had nodular changes that raised questions. The biopsy was necessary to rule out prostate cancer — especially since Bach was considering a surgical procedure for BPH.

****Normally the bladder retains less than 70 ml of urine.

For more about transurethral resection of the prostate (TURP), see "Surgical options."

Diary

Nov. 4, 2011

I underwent a two-hour bipolar TURP under general anesthesia. Dr. DeWolf removed the interior tissue of the prostate capsule using a bipolar cutting tool and flushed the tissue being removed with a saline solution. He retained the tissue for later pathological examination. The tissue left behind was cauterized by the bipolar electrode to minimize bleeding as the area healed. This left a scab and there was little bleeding after the procedure.

I awoke from the operation with little pain and a catheter in place, which was delivering a flushing saline solution to the bladder, providing antibiotics to prevent infection, and draining the bladder. I was transferred to a hospital room, had no appetite, and spent the rest of the afternoon sleeping. I took no pain medicine, only stool softeners.

Nov. 5, 2011

I was considering removal of the catheter and checking out of the hospital late in the day. Dr. DeWolf was skeptical that one day of recovery would be enough, but agreed to removal of the catheter in midafternoon and performance of a post-void residual test to determine if my bladder would be performing adequately to avoid retention of urine.

Removal of the large post-op catheter was painful so soon after the operation, and urination was painful. I was unable to expel enough urine, and ultrasound examination showed that I was retaining more urine than I was able to expel. Therefore my doctors determined that I would have a smaller catheter inserted — for drainage only — and would remain in the hospital for another night.

Nov. 6, 2011

I had the option of having the catheter removed and being tested again for urine retention or going home with the catheter in place in order to give my bladder several more days of rest. I chose to return home with the catheter in place. A surgeon at my local hospital would be providing post-op care.

Nov. 7, 2011

While at home, I noticed that the catheter was not draining, and quickly scheduled a visit to my local surgeon's office. He was able to flush out the catheter with saline solution to remove a blood clot blockage from the head of the catheter. I continued to rest the bladder for two more days.

Nov. 9, 2011

My local surgeon removed the catheter. There was no pain associated with the removal, and after several glasses of water I was able to urinate easily about 1200 ml over the course of the morning. Dr. DeWolf requested that my local hospital perform an ultrasound post-void residual test that afternoon. The result showed that I was retaining almost no urine in the bladder, and therefore the recovery process was continuing normally.

My experience indicates that it was better to leave the hospital with a catheter in place in order to provide several days of rest for the bladder, prior to testing for the return of normal bladder functionality.

Nov. 18, 2011

I have now experienced two weeks of recovery. During that period I continued to urinate normally, with little irritation. Blood clots and scab material continued to be flushed out when I urinated. I spent most of the time for the past two weeks either standing or reclined on a couch reading or working on my laptop computer. I slept well at night and took a nap of about an hour each day. I am looking forward to returning to my normal schedule next week, although I do not expect to be feeling 100% for another month.

I learned the pathology report has come back with the analysis of the tissue removed during the bipolar TURP — and there is no sign of cancer. That is good to know.

Dec. 16, 2011

During my post-op visit, Dr. DeWolf performed a DRE and examined my urine sample under a microscope. He told me that my white blood cell count was elevated, indicating that healing of the prostate was still under way.

I told Dr. DeWolf that a week earlier I experienced some discomfort while urinating and just afterward. After reviewing my urinalysis results, Dr. DeWolf prescribed an antibiotic.

Dec. 26, 2011

The antibiotic helped, and the discomfort while urinating has disappeared. But I continue to avoid spices and acidic food that in the past have irritated my bladder and urinary tract. As the healing process continues, I expect the irritation to subside.

I am very pleased with my ability to urinate easily with a strong stream that allows me to empty my bladder. I would rate my TURP procedure a substantial success. I would recommend bipolar TURP for someone in his 60s or 70s who is seeking a lifetime solution for BPH.

Transurethral electrovaporization of the prostate (TUEVP or TVP). This procedure is similar to TURP in that a resectoscope is inserted into the penis and threaded up into the prostate. But instead of a wire loop that cuts away overgrown prostate tissue, the resectoscope has a roller-ball electrode at the end. Electrical energy quickly heats, vaporizes, and cauterizes prostate tissue, minimizing bleeding. A catheter is then inserted into the bladder.

A meta-analysis of 20 studies examining the safety and effectiveness of TUEVP compared with TURP concluded that, after one year, there was no significant difference in urinary symptom scores or urinary flow rates. The men who underwent TUEVP were significantly less likely to require a blood transfusion. They also spent less time in the hospital and didn't need catheterization for as long as TURP patients. But the TURP patients had a lower risk of urinary retention after the surgery and were less likely to need a second operation compared with TUEVP patients. (To read this study on your own, see "TUEVP for BPH.")

TUEVP for BPH

Poulakis V, Dahm P, Witzsch U, et al. Transurethral Electrovaporization Versus Transurethral Resection for Symptomatic Prostatic Obstruction: A Meta-Analysis. BJU International 2004;94:89–95. PMID: 15217438.

Transurethral incision of the prostate (TUIP). TUIP also involves inserting an instrument into the prostate via the penis. But rather than cutting away excess tissue, the surgeon makes one or more deep lengthwise incisions in the prostate at the site of the urethral constriction. This opens the urethral passage, relieving pressure on the urethra and improving urine flow. Spinal or general anesthesia is generally used for TUIP, which can be performed on an outpatient basis or during a one-day hospital stay. Recovery usually takes five to seven days.

TUIP is not an option for every patient. Men with small prostates are the usual candidates for this procedure. The benefits appear to last: over a five-year period, the chance of needing further surgery is 8% to 10%, somewhat higher than the comparable figure for TURP (5%). There appear to be fewer postoperative complications — including retrograde ejaculation, urinary incontinence, and blood loss — than with TURP. A quarter of men who've undergone TUIP experience retrograde ejaculation, but more than 70% of those who've had TURP do. As a result, most TUIP patients remain fertile after the procedure. Consequently, this option is the one often chosen by men with only moderately enlarged prostates who may still want to father children.

Table 3: BPH procedures compared

Procedure

What's involved

Success rates

Side effects

Transurethral resection of the prostate (TURP)

Performed in operating room

Requires general or spinal anesthesia

May require one to two days in the hospital, with catheter inserted to enable urination for one to three days

Heavy physical activity may be restricted for two weeks or more to prevent bleeding

Full recovery may take four to six weeks

Provides symptom relief in at least 85%–90% of men treated

May cause erectile dysfunction or ejaculatory problems (retrograde ejaculation)

Blood loss, urinary incontinence, infections, and complications from anesthesia are uncommon but do occur

Photoselective vaporization of the prostate (PVP or GreenLight)

Most patients treated in outpatient setting

Catheter remains in place at least overnight for most patients

Patients can resume light activity and return to work within two to three days

Patients can resume vigorous activity in four to six weeks

Improvement in symptom relief similar to TURP

Ejaculatory problems similar to TURP

Less bleeding than TURP

Urinary frequency or urgency in first month

No tissue sample available to check for prostate cancer

Transurethral microwave thermotherapy (TUMT)

Performed on outpatient basis in a doctor's office

Anesthesia not needed, though pain medication and sedatives may be needed

Procedure takes about one hour

Catheter needed for several days

More effective than medication but less effective than TURP

Some urinary side effects, such as frequent urination or discomfort during urination, that can last for several weeks

Risk of reoperation greater than with TURP

Transurethral incision of the prostate (TUIP)

Small incisions are made in the prostate to relieve constriction of the urethra

Requires anesthesia

Hospital stay is typically one to three days

Usually reserved for men with a small prostate

About 80% of patients report an improvement in urinary symptoms

Likelihood of urinary retention is greater than with TURP

Risk of reoperation greater than with TURP

Transurethral electrovaporization of the prostate (TUEVP)

Electrical current vaporizes overgrown prostate tissue

Overnight hospital stay

Catheter needed for one to two days, but usually for less time than with TURP

As effective as TURP at relieving symptoms and improving urine flow, but higher risk of needing second operation

Likelihood of urinary retention is greater than with TURP

Risk of reoperation greater than with TURP

Some urinary side effects, such as blood in the urine and irritation when urinating, that can last for a few weeks

Transurethral needle ablation of the prostate (TUNA)

Done on an outpatient basis

May need local anesthesia

Catheter usually not needed

More effective than medication but less effective than TURP

One study reported that 14% of patients need additional treatments

Side effects, such as erectile dysfunction and urinary incontinence, less common than with TURP

Laser procedures

Laser surgery is widely available for treating BPH. Although usually performed in a hospital setting, laser surgery is less traumatic than TURP, and most patients go home the same day.

To perform a laser procedure, the surgeon begins by guiding a fiber through the urethra to the prostate. This fiber conducts the laser light to the target area. Then the surgeon uses the laser to burn away tissue that obstructs the urine flow. Dead tissue that's not immediately vaporized is later expelled in the urine. This technique destroys prostate tissue with less bleeding than standard TURP. However, because tissue is vaporized, a pathologist cannot check it for cancer, as may be done with TURP.

Surgeons originally used low-energy lasers for these procedures. Now high-energy lasers are becoming more popular. The advantage of these over TURP or low-energy laser sources to remove prostate tissue is that bleeding is reduced and the catheter may be removed much earlier, often within 24 hours. Overnight hospitalization often is not needed. One type of high-energy laser, called a KTP laser, is used during a procedure called photoselective vaporization of the prostate (PVP). During PVP, the surgeon can view the prostate and remove large amounts of tissue with little bleeding (see Figure 8). Indeed, even patients on blood-thinning medication may undergo PVP while still taking their medications.

Figure 8: Photoselective vaporization of the prostate (PVP)

image

When an enlarged prostate obstructs urine flow (A), a relatively new laser technique may be used instead of TURP. During photoselective vaporization of the prostate (PVP), also called the GreenLight procedure, the surgeon threads a thin tube called a cystoscope through the urethra into the enlarged prostate. The surgeon then threads a fiberoptic device through the cystoscope to generate high-intensity pulses of light, which simultaneously vaporize the obstructing tissue and cauterize it to reduce bleeding (B). This creates an enlarged, uniform channel through which urine can flow (C).

Surgeons may also use other types of lasers. For example, procedures using high-energy lasers — like the KTP laser — involve less blood loss, shorter hospital stays, and less time with a catheter compared with TURP. However, use of the holmium laser and its relatives is somewhat limited because they require extensive training and experience compared with the KTP.

Research suggests that patients who have laser procedures are just as likely to experience urinary incontinence and retrograde ejaculation as are those who undergo TURP (see "PVP for BPH").

PVP for BPH

Ruszat R, Wyler SF, Seitz M, et al. Comparison of Potassium-Titanyl-Phosphate Laser Vaporization of the Prostate and Transurethral Resection of the Prostate: Update of a Prospective Non-Randomized Two-Centre Study. BJU International 2008;102:1432–38. PMID: 18671785.

Other treatments for BPH

A variety of other treatments for BPH are in use. Some are not available everywhere, some aren't covered by health insurance, and some are investigational, meaning that they are available only as part of a clinical trial. However, they can be viable options for certain patients with BPH, such as men who aren't healthy enough for surgery.

Transurethral microwave thermotherapy (TUMT). TUMT is one of a group of techniques, known as "heat therapies," that use heat to destroy prostate tissue, achieving results similar to TURP. In TUMT, the doctor guides a thin catheter carrying a miniature microwave generator through the penis to the prostate. There, microwaves destroy some of the prostate tissue and relieve pressure on the urethra (see Figure 9). A cooling jacket around the generator protects the urethra. The procedure takes about an hour and can be performed on an outpatient basis.

Figure 9: Transurethral microwave thermotherapy (TUMT)

image

A thin catheter carrying a miniature microwave generator is guided through the penis to the prostate. Microwaves heat the prostate, destroying the tissue that obstructs urine flow. A computer receives temperature information from the catheter and rectal probe and halts therapy if the areas get too hot.

TUMT appears to be less effective than TURP. A 2001 study reported that 18% of men who underwent TUMT needed additional treatment after 36 months, compared with 13% of those who received TURP. A 2007 analysis of 14 studies of the procedures found that TURP also yielded greater improvements in urine flow and urinary symptoms than TUMT. However, compared with TURP, TUMT results in no blood loss, fewer surgical complications because anesthesia isn't needed, and less risk of retrograde ejaculation. (To read these studies on your own, see "TUMT for BPH.")

TUMT for BPH

Floratos DL, Kiemeney LA, Rossi C, et al. Long-Term Followup of Randomized Transurethral Microwave Thermotherapy Versus Transurethral Prostatic Resection Study. Journal of Urology 2001;165:1533–38. PMID: 11342912.

Hoffman RM, Monga M, Elliot SP, et al. Microwave Thermotherapy for Benign Prostatic Hyperplasia. Cochrane Database of Systematic Reviews 2007;(4):CD004135. PMID: 17943811.

Transurethral needle ablation (TUNA). TUNA is a thermal approach that uses low-level radio waves delivered through twin needles to heat and kill obstructing prostate cells. Shields protect the urethra from damage.

A randomized, prospective clinical trial published in 2004 compared the safety and effectiveness of TUNA with TURP. Researchers at seven centers in the United States enrolled 121 men in the trial; 65 underwent TUNA, and 56 had TURP. Over five years, both groups of men reported significant improvement in symptoms, quality of life, urine flow, and post-void residual volume. But in most cases, the improvements were greater among the TURP patients. Only 1.8% of patients who had TURP needed a second procedure, for example, compared with 13.8% of TUNA patients (see "TUNA for BPH").

TUNA for BPH

Hill B, Belville W, Bruskewitz R, et al. Transurethral Needle Ablation Versus Transurethral Resection of the Prostate for the Treatment of Symptomatic Benign Prostatic Hyperplasia: 5-Year Results of a Prospective, Randomized, Multicenter Clinical Trial. Journal of Urology 2004;171:2336–40. PMID: 15126816.

However, patients undergoing TURP experienced more adverse events or side effects of the procedure than patients undergoing TUNA. For example, the incidence of erectile dysfunction following TUNA was 3.1%, versus 21.4% for TURP. None of the patients in the TUNA group experienced retrograde ejaculation, but 41% of the patients who underwent TURP did.

Prostatic urethral stents. A prostatic urethral stent is a small, springlike mesh cylinder. The doctor inserts the stent through the penis and, after positioning it in the narrowed area of the urethra, releases it to widen the channel, relieving pressure from the prostate tissue and allowing for easier urination. This quick procedure requires only local or spinal anesthesia, involves no loss of blood, and is often done in an outpatient surgical center.

Prostatic urethral stents are most often used in elderly men who have severe prostate enlargement and whose overall health is so poor that surgery would be risky. In many cases, urinary obstruction gradually returns because of a process called hyperplastic epithelial reaction, in which prostate tissue protrudes through the mesh and causes renewed blockage. Additional procedures may be required in some cases.

Ask a doctor

What is prostatic artery embolization? I heard it promoted as an alternative to surgery for BPH. Would you recommend it to your patients?

Embolization is a medical term for using something to plug up a blood vessel. In prostatic artery embolization (PAE), an interventional radiologist uses angiography — a type of real-time imaging that lets doctors see inside blood vessels — to thread a thin catheter into the femoral artery in the groin. The physician then directs the catheter into an artery that supplies the prostate with blood and injects tiny synthetic particles — about the size of fine sand — into the artery to block it. Deprived of the oxygen and nutrients supplied by blood, tissue downstream from the blockage dies off, shrinking prostate tissue and easing pressure on the urethra.

But the research is quite preliminary. Only two studies have been published describing PAE and its outcomes. The first involved two patients, and the second 15 (see "Studies on PAE," below). At a medical conference in 2011, investigators presented unpublished results involving additional patients. Some of the results are indeed promising — but other issues concern me.

Not that many radiologists know how to perform PAE, which is worrisome because one of the challenges of PAE is that the arteries that supply the prostate with blood are closely intertwined with the nerves to the penis, bladder, and rectum. Stopping blood flow to those arteries could indirectly damage organs other than the prostate — resulting in incontinence and erectile dysfunction. And while it is being promoted as "noninvasive," PAE could actually affect the entire prostate, not just the portion that obstructs the urethra.

That's why I'm advising my own patients to wait until the research advances further and we have more information about long-term outcomes.

— Kevin R. Loughlin, M.D., M.B.A.
Professor of Surgery (Urology), Harvard Medical School
Director of Urologic Research, Brigham and Women's Hospital

Studies on PAE

Pisco JM, Pinheiro LC, Bilhim T, et al. Prostatic Arterial Embolization to Treat Benign Prostatic Hyperplasia. Journal of Vascular and Interventional Radiology 2011;22:11–19. PMID: 21195898.

Carnevale FC, Antunes AA, da Motta Leal Filho JM, et al. Prostatic Artery Embolization as a Primary Treatment for Benign Prostatic Hyperplasia: Preliminary Results in Two Patients. Cardiovascular Interventional Radiology 2010;33:355–61. PMID: 19908092.

Botulinum toxin (Botox). Popularly used to minimize facial wrinkles, botulinum toxin is being investigated for relief of urinary symptoms in men with enlarged prostates. It won't shrink your prostate, but small studies have shown that botulinum toxin injections reduced pain and other urinary symptoms — and improved quality of life — for men with BPH. While that may sound promising, there's still a lot that isn't known about using botulinum toxin for the treatment of BPH, such as its long-term effectiveness, its impact on sexual function, the best injection sites, and the appropriate dose. If you decide to try botulinum toxin injections, do so only as a participant in a clinical trial.

NX-1207. This compound apparently works in a different way from other BPH drugs. The studies published so far suggest that it causes prostate cells to die off in an orderly fashion (a process known as apoptosis). A physician injects the drug directly into the prostate by using a catheter that slides into the rectum. Treatment takes place in a physician's office, involves only one injection, and doesn't require anesthesia.

In 2011, the company that makes NX-1207 announced preliminary results of one of its phase III trials — not yet published — that the compound doubled the BPH symptom relief offered by currently available drugs. They also claim that a single injection of NX-1207 can continue working for up to seven-and-a-half years (see "Research on NX-1207").

Research on NX-1207

Shore N. NX-1207: A Novel Investigational Drug for the Treatment of Benign Prostatic Hyperplasia. Expert Opinion on Investigational Drugs 2010;19:305–10. PMID: 20050813.

Too good to be true? Maybe. Independent researchers have expressed skepticism about these results, particularly because the company developing NX-1207 has not made crucial details — such as what exactly the compound is made of — public. Moreover, the phase III results have not yet been published in a peer-reviewed journal — a process that allows independent investigators to evaluate the strength of the findings. So while NX-1207 is worth keeping track of, it's really too soon to say how effective it is.

Author: Harvard Health Publications
Date Last Reviewed: 2/1/2012
Date Last Modified: 9/23/2013
Copyright Harvard Health Publications