Benign Prostatic Hyperplasia (BPH)
Benign prostatic hyperplasia, a noncancerous enlargement of the prostate gland, is the most common benign tumor found in men.
As is true for prostate cancer, BPH occurs more often in the West compared to Eastern countries, such as Japan and China, and may be more common among blacks. Not long ago, a study found a possible genetic link for BPH in men younger than age 65 who have a very enlarged prostate: Their male relatives were four times more likely than other men to need BPH surgery at some point in their lives, and their brothers had a six-fold increase in risk.
BPH produces symptoms by obstructing the flow of urine through the urethra. Symptoms related to BPH are present in about one in four men by age 55, and in half of 75-year-old men. However, treatment is only necessary if symptoms become bothersome. By age 80, some 20 to 30% of men experience BPH symptoms severe enough to require treatment. Surgery was the only option until the recent approval of minimally invasive procedures that open the prostatic urethra and drugs that can relieve symptoms either by shrinking the prostate or by relaxing the prostate muscle tissue that constricts the urethra.
Signs and Symptoms
The symptoms of BPH can be divided into those caused directly by urethral obstruction and those due to secondary changes in the bladder.
Typical obstructive symptoms are:
Difficulty in starting to urinate despite pushing and straining
A weak stream of urine; several interruptions in the stream
Dribbling at the end of urination
Bladder changes cause:
A sudden strong desire to urinate (urgency)
The sensation that the bladder is not empty after urination is completed
Frequent awakening at night to urinate (nocturia)
As the bladder becomes more sensitive to retained urine, a man, may become incontinent (unable to control the bladder causing bed wetting at night, or inability to respond quickly enough to urinary urgency).
Burning or pain during urination can occur if a bladder infection or stone is present. Blood in the urine (hematuria) may herald BPH, but most men with BPH do not have hematuria.
Screening and Diagnosis
The American Urological Association (AUA) Symptom Index provides an objective assessment of BPH symptoms that helps to decide on treatment. However, this index cannot be used for diagnosis, since other diseases can cause symptoms similar to those of BPH.
A medical history will give clues to conditions that can mimic BPH, such as possible stricture, bladder cancer or stones, or abnormal bladder function (problems with holding or emptying urine) due to a neurologic disorder (neurogenic bladder). Strictures can result from urethral damage caused by prior trauma, instrumentation (for example, catheter insertion), or an infection, such as gonorrhea. Bladder cancer is suspected if there is a history of blood in the urine.
Pain in the penis or bladder area may indicate bladder stones or infection. A neurogenic bladder is suggested when an individual has diabetes or a neurologic disease such as multiple sclerosis or Parkinson's disease, or describes a recent deterioration in sexual function. A thorough medical history should also include questions about previous urinary tract infections or prostatitis (inflammation of the prostate that may cause pain in to lower back and the area between the scrotum and rectum, chills, fever, and general malaise), and any worsening of urinary symptoms when taking cold or sinus drugs. The physician will also ask whether any over-the-counter or prescription medications are being taken, because certain varieties can make voiding symptoms worse in men with BPH.
The physical examination may begin with the doctor observing urination to completion to detect any urinary irregularities. The doctor will manually examine the lower abdomen to check for the presence of a mass, which may indicate an enlarged bladder due to retained urine. In addition, a digital rectal exam (DRE) which allows the physician to assess the size, shape, and consistency of the prostate, is essential for proper diagnosis. This important examination involves the insertion of a gloved finger into the rectum, but is only mildly uncomfortable. The detection of hard or firm areas in the prostate raises the suspicion of prostate cancer. If the history suggests possible neurologic disease, the physical may also include an examination for neurological abnormalities that indicate the urinary symptoms result from a neurogenic bladder.
A urinalysis, which is obtained in all patients with symptoms of BPH, may be the only laboratory test if symptoms are mild and no other abnormalities are suspected from the medical history and physical examination. A urine culture is added if a urinary infection is suspected. With more severe chronic symptoms of BPH, blood creatinine of blood urea nitrogen (BUN) and hemoglobin are measured to rule out kidney damage and anemia. Measuring prostate specific antigen (PSA) levels in the blood to screen for prostate cancer is recommended as well as the DRE. PSA testing alone cannot determine whether symptoms are due to BPH or prostate cancer because both conditions can elevate PSA levels.
When is BPH treatment necessary?
The course of BPH in any individual is not predictable. Symptoms, as well as objective measurements of urethral obstruction, can remain stable for many years and may even improve over time as many as one-third of men, according to some studies. In a recent study from the Mayo Clinic, urinary symptoms did not worsen over a three-and-a-half-year period in 73% of men with mild BPH. A progressive decrease in the size and force of the urinary stream and the feeling of incomplete emptying of the bladder are the symptoms most correlated with the eventual need for treatment. Although nocturia (frequent nighttime urination) is one of the most annoying symptoms of BPH, it does not predict the need for future intervention.
If worsening urethral obstruction is left untreated possible complications are: a thickened, irritable bladder with reduced capacity for urine; infected residual urine or bladder stones; and a backup of pressure that damages the kidneys.
Decisions regarding treatment are based on the severity of symptoms (as assessed by the AUA Symptom Index), the extent of urinary tract damage, and the man's and overall health. In general no treatment is indicated in those who have only a few symptoms and are not bothered by them. Intervention -usually surgical- is required in the following situations:
Inadequate bladder emptying resulting in damage to the kidneys
Complete inability to urinate after acute urinary retention
Incontinence due to overfilling or increased sensitivity of the bladder
Infected residual urine
Recurrent severe hematuria
Symptoms that trouble the patient enough to diminish his quality of life
Treatment decisions are more difficult for men with moderate symptoms. They must weigh the potential complications of treatment against the extent of their symptoms. Each individual must determine whether the symptoms bother him enough, or interfere with his life enough, to merit treatment. When selecting a treatment, both patient and doctor must balance the effectiveness of different forms of therapy against their side effects and costs.
Treatment Options for BPH
- Currently, the main treatment options for BPH are:
- Watchful waiting
- Surgery (Prostatic Urethral Lift, Transurethral Resection of Prostate, Photovaporization of the prostate, open prostatectomy)
If medications prove ineffective in a man who is unable to withstand the rigors of surgery, urethral obstruction and incontinence may be managed by intermittent catheterization or an indwelling Foley catheter (which has an inflated balloon at the end to hold it in place in the bladder). The catheter can stay in place indefinitely (in which case, it is usually changed monthly).
Because the progress and complications of BPH are unpredictable, a strategy of watchful waiting-meaning, no immediate treatment is attempted-is best for those with minimal symptoms that are not especially bothersome. Physician visits are needed about once a year to review the progress of symptoms, carry out an examination, and do a few simple laboratory tests. During watchful waiting, the man should avoid tranquilizers and over-the-counter cold and sinus remedies that contain decongestants. These drugs can worsen obstructive symptoms. Avoiding fluids at night may lessen nocturia.
Data is still being gathered on the benefits and possible adverse effects of long-term medical therapy. Currently, two types of drugs-5-alpha-reductase inhibitors and alpha-adrenergic blockers-are used to treat BPH. Preliminary research suggests that these drugs improve symptoms in 30 to 60% of men taking them, but it is not yet possible to predict who will respond to medical therapy, or which drug will be better for an individual patient.
Finasteride (Proscar) blocks the conversion of testosterone to dihydrotestosterone, the major male sex hormone found within cells of the prostate. In some men, finasteride can relieve BPH symptoms, increase urinary flow rate, and actually shrink the size of the prostate, though it must be used indefinitely to prevent recurrence of symptoms. It may take as long as six months, however, to achieve maximum benefits from finasteride.
In a study of its safety and effectiveness two-thirds of the men taking the drug experienced
- At least a 20% decreasen prostate size
- (Only about half had achieved this level of reduction by the one-year mark)
- One-third of patients had improved urinary flow
- And two-thirds felt some relief of symptoms
One study published last year suggests that finasteride may be best suited for men with relatively large prostate glands. An analysis of six studies found that finasteride only improved BPH symptoms in men with an initial prostate volume of over 40 cc (cubic centimeters); finasteride did not reduce symptoms in men with smaller glands. Since finasteride shrinks the prostate, men with smaller glands are probably less likely to respond to the drug because the urinary symptoms result from causes other than physical obstruction (for example, smooth muscle constriction). A recent study showed that over a 4-year period of observation, treatment with finasteride reduced the risk of developing urinary retention or requiring surgical treatment by 50%.
Finasteride use comes with some side effects. Impotence occurs in 3 to 4% of men taking the drug. Men experience a 15% reduction in their sexual function scores, regardless of their age and prostate size. Finasteride may also decrease the volume of the ejaculate. Another adverse effect is gynecomastia (breast enlargement). About 80% of those who stopped taking the drug had a partial or full remission of their breast enlargement. A study from England found gynecomastia in 0.4% of patients taking the drug. Because it is not clear that the gynecomastia is caused by the drug or increases the risk of breast cancer, men taking the drug are being carefully monitored until these issues are resolved. Men exposed to finasteride or dutasteride are also at risk of a condition called post-finasteride syndrome, which is characterized by a constellation of symptoms including sexual (ex: reduced libido, ejaculatory dysfunction, erectile dysfunction), physical (ex: gynecomastia, muscle weakness), and psychological (ex: depression, anxiety, suicidal ideation). These symptoms can persist long-term despite discontinuation of finasteride.
Finasteride can lower PSA levels by about 50%, but is not thought to limit the utility of PSA as a screening test for prostate cancer. The fall in PSA levels, and any adverse effects on sexual function, disappear when finasteride is stopped.
To get the benefits of finasteride for BPH without compromising the detection of early prostate cancer, men should have a PSA test before starting treatment with finasteride; subsequent PSA values can then be compared to this baseline value. If a man is already on finasteride and no baseline PSA level was obtained, the results of a current PSA test should be multiplied by two to estimate the true PSA level. A fall in PSA of less than 50% after a year of finasteride treatment suggests either that the drug is not being taken or that prostate cancer might be present. Any increase in PSA levels while taking finasteride also raises the possibility of prostate cancer.
These drugs, originally used to treat high blood pressure, reduce the tension of smooth muscles in blood vessel walls and also relax smooth muscle tissue within the prostate. As a result, daily use of an alpha-adrenergic drug may increase urinary flow and relieve symptoms of urinary frequency, and nocturia. A number of alpha-l-adrenergic drugs-doxazosin (Cardura), prazosin (Minipress), terazosin (Hytrin),and tamsulosin (selective alpha I-A receptor blocker- FLOMAX) for example-have been used for this purpose. One recent study found that 10 mg of terazosin daily produced a 30% reduction of BPH symptoms in about two-thirds of the men taking the drug. Lower daily doses of terazosin (2 and 5 mg) did not produce as much benefit as the 10 mg dose. Thus, the authors of this report recommended that physicians gradually increase the dose to 10 mg unless troublesome side effects occur. Possible side effects of alpha-adrenergic blockers are: orthostatic hypotension (dizziness upon standing, due to a fall in blood pressure), fatigue, and headaches. In this study, orthostatic hypotension was the most frequent side effect. The authors noted that this problem can be mitigated by taking the daily dose of the drug in the evening. In another study of over 2,000 BPH patients, a maximum of 10 mg of terazosin reduced average AUA Symptom Index scores from 20 to 12.4 over one year, compared to a drop from 20 to 16.3 in patients taking a placebo. Another troubling side effect of alpha-blockers is the development of ejaculatory dysfunction (up to 16% of patients will experience this).
An advantage of alpha blockers, compared to finasteride, is that they work almost immediately; they have the additional benefit of treating hypertension when it is present in BPH patients. However, whether terazosin is superior to finasteride may depend more on the size of the prostate. When the two drugs were compared in a study published in The New England Journal of Medicine, terazosin appeared to produce greater improvement of BPH symptoms and urinary flow rate than finasteride. But this difference may have been due to the larger number of men in the study with small prostates, who would be more likely to have BPH symptoms from smooth muscle constriction, rather than from physical obstruction by excess glandular tissue. Doxazosin was evaluated in three different clinical studies involving 337 men with BPH. Patients took either a placebo or 4 to 12 mg of doxazosin a day. The active drug- reduced urinary symptoms by 40% more than the placebo, and increased urinary peak flow by an average of 2.2 ml/s (compared to 0.9 ml/s in the placebo patients).
Despite the previously held belief that doxazosin was only effective for mild or moderate BPH, patients with severe symptoms experienced the greatest improvement. Side effects-including dizziness, fatigue, hypotension (low blood pressure), headache, and insomnia-led to withdrawal from the study by 10% of those on the active drug, and 4% of those taking the placebo. In men treated for hypertension, the doses of other antihypertensive drugs may need to be adjusted to account for the blood-pressure-lowering effects of an alpha-adrenergic blocker. These drugs may also induce angina in men with coronary heart disease. A doctor will be able to determine which individuals are good candidates for their use.
Phosphodiesterase 5 Inhibitors
Phosphodiesterase 5 inhibitors, such as cialis, are commonly used for erectile dysfunction; however, when used daily also possess the ability to relax the smooth muscle of the prostate and overactivity of the bladder muscle. Studies examining the impact of daily cialis use compared to placebo demonstrated a reduction in IPSS scores by 4-5 points and was superior to placebo in reducing urinary frequency, urgency and urinary incontinence episodes. Studies examining the impact of cialis on urine flow, however, have not shown meaningful change in the rate of urine flow.
Surgical treatment of the prostate involves the displacement or removal of the obstructing adenoma of the prostate. Surgical therapies have historically been reserved for men who failed medical therapy, developed urinary retention secondary to BPH, developed recurrent urinary tract infections, bladder stones, and/or developed bleeding from the prostate. However, a large number of men are poorly compliant with medical therapy due to side effects. Therefore, surgical therapy can be considered in these men to prevent deterioration of bladder function long-term.
Current surgical options include monopolar and bipolar transurethral resection of the prostate (TURP), robotic simple prostatectomy (retropubic, suprapubic, and laparoscopic), transurethral incision of the prostate, bipolar transurethral vaporization of the prostate (TUVP), photovaporization of the prostate (PVP), Prostatic urethral lift (PUL), thermal ablation using transurethral microwave therapy (TUMT), water vapor thermal therapy, transurethral needle ablation (TUNA) of the prostate, enucleation using Holmium or Thulium laser (HoLEP or ThuLEP).
Thermal procedures alleviate symptoms by utilizing convective heat transfer generated from a radiofrequency generator. Transurethral needle ablation (TUNA) of the prostate uses low-energy radio waves, delivered by tiny needles at the tip of a catheter, to heat prostatic tissue. A six-month study of 12 men with BPH (age 56 to 76) found the treatment reduced AUA Symptom Index scores by 61%, and produced minor side effects (including mild pain or difficulty urinating for 1 to 7 days in all the men). Retrograde ejaculation occurred in one patient. Another thermal treatment, transurethral microwave thermotherapy (TUMT), is a minimally invasive alternative to surgery for patients with bladder outflow obstruction caused by BPH. Performed on an outpatient basis under local anesthesia, TUMT damages prostatic tissue by microwave energy (heat) that is emitted from a urethral catheter.
A new form thermal therapy, called water vapor thermal therapy or Rezum, involves conversion of the thermal energy into water vapour to cause cell death in the prostate. Studies examining the 6-month prostate size after water vapor thermal therapy demonstrated a 29% reduction in prostate size by MRI.
With thermal therapies, several treatment sessions may be necessary, and most men-will need additional treatment for BPH symptoms within five years after their initial thermal treatment.
Transurethral incision of the prostate (TUIP)
This procedure was first used in the U.S. in the early 1970s. Like TURP, it is done with an instrument that is passed through the urethra. But instead of removing excess tissue, the surgeon only makes one or two small cuts in the prostate with an electrical knife or laser. These incisions relieve pressure on the urethra. TUIP can only be done on men with smaller prostates. It takes less time than TURP, and can be performed on an outpatient basis under local anesthesia in most cases. A lower incidence of retrograde ejaculation is one of its advantages.
Prostatic Urethral Lift (Urolift)
In contrast to the other therapies that ablate or resect prostate tissue, the prostatic urethral lift procedure involves placing Urolift implants into the prostate under direct visualization to compress the prostate lobes and unobstruct the prostatic urethra. The implants are placed using a needle that passes through the prostate to deliver a small metallic tab anchoring it to the prostate capsule. Once the capsular tab is placed, a suture connected to the capsular tab is tensioned and a second stainless steel tab is placed on the suture to lock it into place and the suture is severed.