Benign prostatic hyperplasia
Description
An in-depth report on the causes, diagnosis, treatment, and prevention of BPH.
Alternative Names
Enlarged prostate
Medications
The two primary drug classes used for BPH are:
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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.
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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, researchers are investigating combinations of the two are for selected patients. Results from the Medical Therapy of Prostatic Symptoms (MTOPS) trial, published in 2003, reported that a combination of doxazosin and finasteride delayed progression of BHP more effectively than either drug alone. The combination treatment may work best for high-risk patients with larger prostate glands and higher PSA readings. Many men 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 do not affect PSA levels nor do they shrink the size of the prostate. Research also indicates that they may even promote a natural process called apoptosis, in which cells in the prostate gland self-destruct. Investigators are studying whether these drugs may help prevent the development of prostate cancer.
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 BPH treatment. 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), doxazosin (Cardura), and alfuzosin (Uroxatral). Alfuzosin is the newest drug 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 drugs work within a few weeks, are inexpensive, and produce long-lasting benefits. Alfuzosin begins to improve urine flow within hours.
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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 extended-release formulation appears to pose a much lower risk than the other 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 common side effect of alpha-blockers, as it is with finasteride.)
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Long-Term Effects. These drugs slow the progression of BPH but do not help prevent urinary retention.
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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 drug under investigation. These drugs target receptors that affect only 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 drugs 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) 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 the alpha-blocker doxazosin.) 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 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:
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Very large prostates (40 mL or larger)
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Low urinary flow rates
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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, which are measured for screening prostate cancer. Lower PSA levels may mask the presence of the cancer. 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:
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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 in most men who take finasteride.
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Reductions in energy.
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Breast tenderness.
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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.
Alternative Medicines
Popular herbal treatments for BPH include:
Saw Palmetto.
Saw palmetto is one of the most popular herbal remedies for BPH. It comes from the berry of the plant Serenoa repens. A major 2006 study in the
New England Journal of Medicine
found that saw palmetto had no benefit for treating BPH. The study enrolled 225 men with moderate-to-severe BPH. The men received either placebo or 160 mg of saw palmetto twice daily. After 1 year, there were no differences in symptom improvement between the placebo and saw palmetto groups.
Beta-Sitosterol.
Beta-sitosterol preparations come from South African star grass, Hypoxis rooperi, and other plant species. Some studies have shown beta-sitosterol to improve urinary symptoms and flow. They may increase the risk for impotence, however.
Pygeum Africanum.
Pygeum Africanum
is an extract from the bark of an African plum tree. In an analysis of 18 trials, the herb provided a moderate improvement in urinary symptoms compared to placebo. Side effects were mild. The studies were short in length, however.
Cernilton.
Cernilton is prepared from rye grass pollen. Studies have been limited, but some suggest it may help improve symptoms, including nighttime urinary problems. Other studies have found no benefit.
Other popular herbs include nettle root extract (
Urtica dioica
) and pumpkin seed oil (
Cucurbita peponis
). There is no scientific evidence that any of these remedies help treat BPH.
Herbs and Supplements
Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Patients should check with their doctor before using any herbal remedies or dietary supplements.
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Investigational Drugs
Botulinum.
Botulinum toxin A (Botox) injections, a common wrinkle treatment, cause small muscles to relax. This approach is now being investigated for treating many disorders that involve overexcited muscle activity, including benign prostatic hyperplasia. Preliminary studies are showing promising results in improving urine flow and reducing urinary retention.
PDE5 Inhibitors
. Phosphodiesterase-5 (PDE5) inhibitors can 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. Research presented at the 2006 American Urological Association meeting suggested that sildenafil improves urinary symptoms in men who have both ED and LUTS. Another study indicated that a combination of sildenafil and the alpha-blocker alfusozin (Uroxatral) worked better for treating LUTS and ED than either drug alone.
Other Areas of Investigation.
Researchers are looking at several different drugs for future BPH therapies. Most drugs 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.
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Review Date: 6/26/2006
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Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital
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