Medications:

The two primary drug classes used for BPH are:

• Alpha-blockers. These drugs relax smooth muscles, especially in the urinary tract and prostate. They include terazosin (Hytrin), doxazosin (Cardura), tamsulosin (Flomax), and alfuzosin (Uroxatral). Alpha-blockers help relieve BPH symptoms, but they do not reduce the size of the prostate. The can help improve urine flow and reduce risk of bladder obstruction. They are often the first choice, especially for men with smaller prostates.
• 5-alpha-reductase inhibitors. Finasteride (Proscar) and dutasteride (Avodart) block the conversion of testosterone to dihydrotestosterone, the male hormone that stimulates the prostate. These drugs are better for men with significantly enlarged prostates. In addition to relieving symptoms, they increase urinary flow and may even help shrink the prostate. However, patients may have to take these drugs for up to 6 - 12 months to achieve full benefits.

Because these two types of drugs work in different ways, combinations of the two may control symptoms in select patients more effectively than either drug alone. The combination treatment may work best for patients with larger prostate glands and higher PSA readings. Many men, however, can control their condition with a single drug.

Alpha-Adrenergic Antagonists (Alpha-Blockers)

General Guidelines for Alpha-Blockers. Alpha-adrenergic antagonists, commonly called alpha-blockers, were originally used to treat high blood pressure. They are prescribed for BPH to relax smooth muscles in the prostate. The muscle cells in the prostate are stimulated by molecules called alpha adrenergic receptors. This can cause lower urinary tract symptoms.

Drugs that block these receptors relax the muscles in and around the prostate, increase urinary flow and improve symptoms, sometimes significantly. Improvement occurs within days to weeks. Because these drugs are short-acting, symptoms return very quickly once a man stops taking the medication. They neither affect PSA levels nor shrink the size of the prostate.

Alpha-blockers are prescribed for most men with BPH symptoms whose prostates are not significantly enlarged. Even men with moderately enlarged prostates might try alpha-blockers before more intense treatments because these drugs work fairly quickly, have no effect on sexual drive, and are the least expensive treatment for BPH. Some experts now recommend alpha-blockers as first-line treatment for patients with moderate-to-severe symptoms.

These drugs are generally referred to as either nonselective or selective alpha-blockers. Drugs in both categories are similar in effectiveness for reducing symptoms and improving urinary flow. There are some differences, however. Patients should discuss the appropriate alpha-blocker for their individual condition with their doctors.

Nonselective Alpha-Blockers. Nonselective alpha-blockers (also referred to as alpha-specific antagonists) include terazosin (Hytrin) and doxazosin (Cardura). They relax all smooth muscles, not only in the prostate but also those that surround any blood vessel in the body. These drugs work within a few weeks, are inexpensive, and produce long-lasting benefits.

• Side Effects. Nonselective alpha-blockers can reduce blood pressure, which may cause dizziness, headache, rapid heartbeat, and fatigue. Orthostatic hypotension, a sudden drop in blood pressure when standing, can occur and increases the risk of falling. Taking the medication close to bedtime can help reduce these side effects. Because of the reduced blood pressure side effect, do not take phosphodiesterase inhibitors [such as sildenafil (Viagra)] at the same time, at least without advice from a doctor. (Alfuzosin's extended-release formulation appears to pose a much lower risk for side effects than other alpha-blocker drugs.) Alpha-blockers can also cause headache, sore throat, and weakness. Nasal congestion occurs in about 2% of cases. Men may also experience a decreased ejaculate. (Impotence is not a usual side effect of alpha-blockers, as it is with finasteride and dutasteride.)
• Long-Term Effects. These drugs may control the symptoms of BPH but do not prevent urinary retention.
• Best Candidates. Nonselective alpha-blockers may be a good choice for many men with severe urinary problems.

Selective Alpha-Blockers. Tamsulosin (Flomax) and alfusozin (Uroxatral) are the only selective alpha-blocker (sometimes called alpha1A-urospecific antagonists) approved for treatment of BPH. These drugs target receptors that affect only the smooth muscles of the prostate. They seem to work as well as nonselective alpha-blockers.

Selective alpha-blockers appear to be very safe, even for years. Side effects are minimal. Most common ones include nasal congestion. The risk for low blood pressure and dizziness is lower than with the nonselective alpha-blockers. They may pose a higher risk for problems in ejaculation than nonselective alpha-blockers, but do not appear to cause impotence or reduce sexual drive as finasteride does. These drugs can interact with certain medications, including calcium channel blockers (particularly verapamil).

Antimuscarinics. A combination of alpha-blockers and antimuscarinics drugs have been evaluated in a few trials. These drugs, used to treat urinary incontinence, inhibit involuntary contractions of the bladder. One trial demonstrated that a combination of tolterodine (Detrol) and tamsulosin worked better than either drug alone for men with lower urinary tract symptoms (LUTS), including overactive bladder.

Finasteride and Other 5-Alpha-Reductase Inhibitors

Specific Benefits. The prostate gland contains an enzyme called 5 alpha-reductase that converts testosterone to another androgen called dihydrotestosterone. Finasteride (Proscar) and dutasteride (Avodart), known as a 5-alpha-reductase inhibitors, block this enzyme and thus reduce dihydrotestosterone in the prostate.

Finasteride is not as effective as alpha-blockers in improving BPH and urinary tract symptoms, but it can be helpful. Follow-up studies have reported that the drug is safe and effective over the long term. The 5 alpha-reductase inhibitors are perhaps most effective in reducing symptoms in men with large prostates. (Men with larger prostates and high PSA values may also benefit from combination therapy of finasteride and an alpha-blocker.) In such cases, studies on finasteride also suggest the medicine reduces the risk of acute urinary retention and the need for surgery. It also helps control bleeding in the urine that is related to BPH. A side benefit of finasteride is reduction of hair loss related to male hormones and, in some cases, hair growth in men with mild-to-moderate male pattern baldness.

Dutasteride (Avodart) is a newer drug that inhibits two types of the 5-alpha-reductase enzymes and achieves a more rapid suppression of dihydrotestosterone than finasteride. A 4-year study reported sustained improvements in urinary symptoms and prostate volume reduction. Comparison studies are needed to determine if the dual actions of dutasteride offer significant benefits over those of finasteride. Researchers are also investigating whether dutasteride can help prevent the development of prostate cancer.

Candidates. Some experts recommend 5-alpha-reductase inhibitors for men of any age who have all three of the following conditions:

• Very large prostates (40 mL or larger)
• Low urinary flow rates
• Prostate enlargement related primarily to hormone-stimulated overgrowth of glandular tissue

Finasteride is also proving to be helpful for patients who have hematuria (blood in the urine) related to BPH.

Dosing. Finasteride and dutasteride are taken once a day. It may take as long as 6 - 12 months for a man to notice a change in symptoms.

Effects on PSA. Finasteride and dutasteride decrease prostate-specific antigen (PSA) levels. These lowered PSA levels may affect the results of PSA tests and mask the presence of prostate cancer. To resolve this problem, doctors calculate PSA levels in men taking these drugs by doubling the PSA values. Studies confirm that this doubling equation helps provide an accurate measurement.

Side Effects. Finasteride has been associated with:

• Sexual dysfunction, including low sexual drive and impotence, in about 6 - 19% of patients. Such problems appear to occur only during the first year of use and diminish over time.
• Reductions in energy.
• Breast tenderness.
• Possible weight loss in some men.

Other Anti-Androgens

Other anti-androgens, including drugs known as gonadotropin-releasing hormone agonists, are effective against BPH, but they can reduce sexual drive and are much more likely to cause impotence. Flutamide is an anti-androgen that may be an alternative to surgery in certain patients with BPH who have physical or mental disorders.

Investigational Drugs

Botulinum. Botulinum toxin A (Botox) injections cause small muscles to relax. This approach is now being investigated for treating many disorders that involve overexcited muscle activity, including BPH. Preliminary studies are showing potential benefit in improving urine flow and reducing urinary retention in men with more severe symptoms. However, there are a few published studies evaluating its use.

PDE5 Inhibitors. Phosphodiesterase-5 (PDE5) inhibitors are used to treat erectile dysfunction (ED). They include sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). Because lower urinary tract symptoms (LUTS) and ED often occur together in older men, researchers are investigating whether PDE5 inhibitors may help improve BPH symptoms. Some studies indicate that sildenafil improves urinary symptoms in men who have both ED and LUTS. It is also being evaluated in combination with selective alpha-blocker drugs.