Prostate Enlargement

Medications that treat BPH

Before suggesting surgery, your doctor is likely to recommend medication for BPH (see Table 1). 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 3).

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.

In 2011, the FDA approved the first PDE5 inhibitor, tadalafil, for use in treating BPH and the combination of erectile dysfunction and BPH. 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. When used to treat BPH (with or without erectile dysfunction), the medication is taken at a 5 mg dose once daily.

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.

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.

An 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. Subsequently a study involving 3,040 men showed that finasteride provided significant benefits for men with symptoms of urinary obstruction and prostatic enlargement. 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. Researchers have also 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.

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.

Finasteride and dutasteride can interfere with sexual function. 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.

In 2012, based on reports it received from doctors and patients, the FDA revised the finasteride label to warn about possible sexual side effects. Men who use this drug for BPH should be aware that it may cause poor semen quality (contributing to infertility) and erectile dysfunction, although both problems should improve once they stop taking it. However, the drug may also depress libido, and the FDA warns that this problem may continue even after stopping the drug.

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. In 2012, a randomized controlled study reported that tadalafil worked as well as the alpha-blocker tamsulosin. Based on this evidence, an advisory committee in Europe recommended that the option become available in Europe as well.

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.

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 (serenoa repens). 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 review conducted for the Cochrane Collaboration, an international group of experts, examined 17 randomized controlled trials that compared saw palmetto with placebo. The review found that saw palmetto was no better than a placebo at improving urinary flow or otherwise relieving symptoms of BPH—even in studies where saw palmetto was given at double or triple the usual dose.

One of the studies include in the review was a federally funded trial published in 2011. 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.

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.

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 2.

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 4). 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.

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.

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.

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.

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.

Laser procedures

Laser surgery is widely available for treating BPH, and is increasingly being used instead of TURP. 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 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.

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 5). Indeed, even patients on blood-thinning medication may undergo PVP while still taking their medications.

Laser procedures have increased in popularity over the past decade. One analysis of data in Florida—a state with a large elderly population and thus, presumably, men affected by BPH—found that laser procedures had increased 400% between 2001 and 2009. In a surprise, however, the patients least likely to receive laser treatment for BPH were men who were older or in ill health, two factors that might make an office-based laser procedure seem more appealing than going into the hospital for TURP.

There is no proof yet that laser procedures are any better than TURP in the long term. 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. And a large study reported in 2012 that men who undergo laser procedures are more likely to need additional treatment for BPH symptoms than those who undergo TURP. The study found that about 8% of men who underwent TURP needed another procedure within four years, compared with 13% of men who had a laser procedure.