Benign Prostatic Hyperplasia

Description

Alternative Names

Medications

The two primary drug classes used for BPH are the following:

• Alpha-blockers. These drugs relax smooth muscles, especially in the urinary tract and prostate. They include terazosin (Hytrin), doxazosin (Cardura), tamsulosin (Flomax), and alfuzosin (Xatral). Alpha-blockers are more likely to reduce symptoms of BPH and are often the first choice, particularly in men with smaller prostates.
• 5-alpha-reductate inhibitors. Finasteride (Proscar), the standard a5-alpha-reductate inhibitor, blocks male hormones, particularly dihydrotestosterone. Such agents may help men with significantly enlarged prostates.

Because the two drug classes have different mechanisms, combinations of the two are being investigated for selected candidates. Although studies have been mixed, a well-conducted 2003 study reported that a combination of doxazosin and finasteride delayed progression of BHP more effectively than either drug alone. (Another 2003 study found no additional benefit from finasteride.) The combination is expensive, in any case, and many men can control their condition with a single agent.

Alpha-Adrenergic Antagonists (Alpha-Blockers)

General Guidelines for Alpha-Blockers.Alpha-adrenergic antagonists, commonly called alpha-blockers, 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 then 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 do not affect PSA levels. Research also indicates that they may even promote a natural process called apoptosis, in which cells in the prostate gland self-destruct.

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

These agents 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), doxazosin (Cardura), and alfuzosin (Xatral). Alfuzosin is the newest agent and can be taken once a day. They relax all smooth muscles, not only in the prostate but also those that surround any blood vessel in the body. These agents work within a few weeks, are inexpensive, and produce long-lasting benefits. (Alfuzosin, the newest agent, begins to improve urine flow within hours.)

• 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. (Alfuzosin's prolonged-release formulation appears to pose a much lower risk than the other agents.) 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 common side effect of alpha-blockers, as it is with finasteride.)
• Long-Term Effects. These agents are useful in reducing high blood pressure and may have some benefits in improving unhealthy cholesterol levels. These agents also may help reduce the risk for prostate cancer cell growth through apoptosis -- a process in which cells self-destruct.
• Interactions. These agents should not be taken with drugs that are cytochrome P3A4 inhibitors, which include erythromycin, ketoconazole, itraconazole and others.
• Best Candidates. Nonselective alpha-blockers may be a good choice for many men with severe urinary problems and especially those with hypertension, high cholesterol levels, or both. However, alpha-blockers can exacerbate heart failure symptoms in men with this condition.

Selective Alpha-Blockers. Tamsulosin (Flomax) is the only selective alpha-blocker (sometimes called alpha1A-urospecific antagonists) approved to date. Naftopidil is a similar agent under investigation. These agents target receptors that only affect the smooth muscles of the prostate. Tamsulosin appears to be similar in effectiveness to the nonselective alpha-blockers. It is not clear if it reduces long-term complications of BPH.

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 agents can interact with certain medications, including calcium channel blockers (particularly verapamil).

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), known as a 5-alpha-reductase inhibitor, blocks this enzyme and so suppresses dihydrotestosterone and reduces the size of the prostate.

Finasteride is not as effective as alpha-blockers in improving BPH and urinary tract symptoms, but they can be helpful. Follow-up studies in 2003 of six to ten years have reported that the drug is safe and effective over the long term. The 5 alpha-reductase inhibitors are perhaps most effective in reducing the size of large prostates. In such cases, studies on finasteride also suggest it 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 agent that inhibits two types of the 5-alpha-reductase enzymes and achieves a more rapid suppression of dihydrotestosterone than finasteride. Studies are reporting significant improvement in symptoms. Its effect on prostate cancer is not known. Comparison studies are needed to determine if the dual actions of dutasteride offer significant benefits over those of finasteride.

Candidates for Finasteride (Proscar). Some experts now believe that finasteride is most useful 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 very effective for patients who have hematuria (blood in the urine) related to BPH.

Administering Finasteride (Proscar). Finasteride is taken once a day. It may take as long as six months for a man to notice a change in symptoms.

Effects on PSA. Finasteride reduces levels of a factor called prostate-specific antigen (PSA) levels, which is measured for screening prostate cancer. Lower PSA levels then may mask the presence of the cancer. A more recent test that measures so-called free PSA may be accurate, regardless of whether men are taking finasteride or not.

Side Effects. Finasteride has been associated with:

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

Animal studies have reported that the drug enters semen and may cause fetal abnormalities, but studies on humans have not reported such effects.

Other Anti-Androgens

Other anti-androgens, including drugs known as gonadotropin-releasing hormone agonists, are effective against BPH, but 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.

Alternative Medicines

Patients with chronic conditions are often tempted to try alternative treatments, including herbs and other nontraditional therapies. It is certainly possible that some herbal medicines may be helpful, but none are regulated and their quality and safety cannot be guaranteed. No one should take any herbal medication or attempt to self-treat BPH without first consulting a physician.

Saw Palmetto. Saw Palmetto is derived from the berry of the plant Serenoa repens. As with all herbal remedies, saw palmetto is not regulated. A private testing group reported that saw palmetto products sold in major drugstore and health food chains (CVS, GNC, Centrum, Celestial Seasonings, Natrol, Natures Way, Bayer, Walmart, Walgreens, Amway, and others) met quality requirements.

• Actions and Benefits. Studies on saw palmetto are mixed. In one 2003 study, for example, saw palmetto was no more effective than placebo. Other have reported some it to be as effective as to finasteride (Proscar) in reducing symptoms and increasing urinary flow and to have fewer side effects. (Alpha-blockers are more effective than either agent, however.)
• Side Effects. Saw palmetto does not cause impotence, which occurs in some men taking finasteride. There have been reports of increased bleeding during surgery with the use of this herb. Gastrointestinal problems have been reported and the herb may aggravate chronic gastrointestinal diseases, such as peptic ulcers, gastroesophageal reflux, and ulcerative colitis. Some experts suggest it be taken with food.
• Candidates. Some experts believe that saw palmetto, purchased from a reliable store, is a safe and possibly effective option for men with mild to moderate symptoms from BPH who are seeking a natural product with no known major side effects to date.

Beta-Sitosterol Preparations. Beta-sitosterol preparations (e.g., Harzol) are derived from South African star grass, Hypoxis rooperi, and other plant species. They have been shown to improve urinary symptoms and flow in four well-conducted studies. They may increase the risk for impotence, however. Long-term effectiveness and safety are unknown. Standardized preparations and comparison trials with standard agents are needed.

Pygeum Africanum. Pygeum Africanum (Tadenan) is an extract from the bark of an African plum tree. In an analysis of 18 trials, the agent provided a moderate improvement in urinary symptoms compared to placebo. Side effects were mild. The studies were small and of short duration, however. The preparations used were also not standardized, and comparison trials with standard agents are needed.

Cernilton. Cernilton is prepared from rye grass pollen. Studies have been limited but the available evidence suggests it may help improve symptoms, including nighttime urinary problems.

Bowman-Birk Inhibitor. Bowman-Birk inhibitor is a soybean-derived product that is being investigated for its effects on prostate health and possible prevention of prostate cancer. A 2001 trial of a concentrated form found it provided a significant decrease in serum PSA levels, in serum triglyceride levels, and in prostate volume. It may also improve urinary symptoms. There is some concern, however, that such agents may increase the risk for pancreatic cancer.

Investigative Agents

Botulinum. Botulinum toxin A (Botox) injections, a common wrinkle treatment, causes small muscles to relax. This approach is now being investigated for treating many disorders that involve over-excited muscle activity, including benign prostatic hyperplasia. In one early study, men with severe symptoms but who did not want surgery reported symptom reduction of 65% two months after injections.

Other Areas of Investigation. Researchers are looking at a number of different agents for future BPH therapies. Most agents being researched for BPH, such as arylpiperazines, target molecules in the prostate that may help suppress cell growth. Some efforts are focusing on drugs that affect the central nervous system or nerve fibers in the bladder and urethra to reduce urinary tract symptoms.