Benign Prostatic Hyperplasia

Authors: Drs Marshall Stoller (university of California SF) and Aaron Berger (Chicago) 2008-10-13
What is Benign Prostatic Hyperplasia (BPH)?

Benign prostatic hyperplasia (BPH) is an enlargement of the prostate gland that occurs commonly as men age. This enlargement can contribute to bothersome lower urinary tract symptoms (LUTS) and may include: urinary frequency, urgency of urination, nocturia or waking up at night to urinate, weak urinary stream, sensation of incomplete bladder emptying, and dribbling after urination. This constellation of symptoms known as LUTS is likely caused not only by BPH, but also by changes that occur in the bladder as a result of aging or as a result of changes brought on by BPH. BPH affects about half of men over the age of 50 and increases to 90% or more for men in their 80’s.

What exactly is the prostate?

The prostate gland is located between the bladder and the penis and secretes some of the seminal fluid that is released during ejaculation (Figure 1). The urethra, the tube running from the bladder through the penis where the urine passes, traverses through the prostate. In BPH, the more central portion of the prostate gland becomes enlarged and subsequently can obstruct the flow of urine traveling from the bladder.

Figure 1:  Cross-sectional view of the male pelvis showing the location of the prostate in relation to the bladder, urethra, and rectum.
 

How is BPH diagnosed?

A detailed medical history, especially focusing on urinary symptoms, is essential in the diagnosis of BPH. It is important to rule out more serious causes of urinary complaints such as prostate or bladder cancer. This urinary history can include a survey called the American Urological Association (AUA) Symptom Score (Figure 2) or International Prostate Symptom Score (IPSS) which assesses and assigns point values to several urinary symptoms, but also determines how bothersome the symptoms are to the patient.

Figure 2:  The American Urological Association (AUA) symptom score used to assess the severity of urinary symptoms (also known as International Prostate Symptom Score).

In addition to the history, a digital rectal exam (DRE) is used to evaluate prostate size as well as to determine if there is prostatic pain or tenderness which may be indicative of prostatitis, an inflammatory condition of the prostate which can cause bothersome urinary symptoms. While it is not possible to get an exact prostate measurement based on the DRE, an experienced urologist will be able to make a good estimate based on prior experience. However, prostate size does not necessarily correlate with the degree of symptoms. Patients with very large prostates may have no urinary symptoms and other patients with only mild BPH may have very bothersome symptoms.

During evaluation of urinary symptoms, a urinalysis should be performed to assess for any signs of infection or any blood in the urine, which could be an indication of a more serious problem. However, large prostates may sometimes bleed spontaneously, especially with strenuous activity or in patients on anticoagulation medication. A prostate specific antigen or PSA may also be checked as a screening test for prostate cancer, especially in men over age 50, or for patients with a family history of prostate cancer. An additional urine test, called a cytology, may be obtained if the urinary symptoms are mainly frequency and urgency. This test is utilized to evaluate for potential bladder tumors.

There are several other tests which are commonly used to better evaluate LUTS which may be caused by BPH. A non-invasive urinary flow rate, or uroflow, is a test whereby the patient urinates into a machine which measures the flow of urine over time. This exam is often followed by a measurement of the urine left in the bladder when urination is complete which is called the post-void residual (PVR). Normally, there should be little or no residual urine present and high PVRs can be indicative of obstruction from BPH, a poorly functioning bladder, or both. The PVR can be measured either by placing a catheter into the bladder to drain any residual urine or by a BladderScan device which is a type of ultrasound that measures the urine in the bladder.

If these non-invasive tests are not conclusive in determining the cause of urinary symptoms or if surgery is being considered for the management of BPH, urodynamics are often performed. This diagnostic test involves the placement of small catheters into both the bladder and rectum. As the bladder is filled, the pressure is recorded and when the bladder is full, the patient is asked to urinate and the flow rate and bladder pressure are recorded. Obstruction from BPH typically demonstrates a high bladder pressure and a low flow rate. X-ray images may also be used during this examination to evaluate for bladder shape and size, to determine if any stones are present in the bladder, and to determine if there is an outpouching of the bladder that is called a diverticulum.

Another diagnostic test which may be utilized, but which is not part of the standard BPH evaluation, is cystoscopy. This is an outpatient procedure where a small, flexible or rigid telescope is placed into the urethra and bladder. This can be useful to rule out the presence of a stricture or narrowing in the urethra, and may also give the urologist an idea of how large and obstructing the prostate actually is. Finally, an abdominal or transrectal ultrasound may be performed to get a more accurate measurement of prostate size, as this may help the urologist to predict what type of therapy is appropriate.

Risks of delaying or not seeking treatment:

BPH is a disease process which may not cause any symptoms or may cause significant bother. In addition to the quality-of-life symptoms, more serious complications can occur. If there is a significant amount of urine left in the bladder after urination is complete, called a post-void residual, patients are more likely to develop urinary tract infections and/or bladder stones. With a large obstructive prostate, the bladder pressure needed to empty the bladder is higher than normal and this high pressure can cause diverticuli to form in the bladder wall and these also can lead to the formation of infections or stones, as they often do not empty. In rare cases, high residuals and high bladder pressures can obstruct the kidneys and lead to loss of renal function. Furthermore, with long term obstruction from BPH, changes can occur in the bladder wall muscle which can lead to irreversible bladder dysfunction. Occasionally, obstruction from BPH is so severe that patients may be unable to urinate at all, a condition called urinary retention, and a catheter must be placed emergently into the bladder. While this condition often can be reversed with medical or surgical management, sometimes it is permanent and patients must live with an indwelling catheter. Another option for patients who cannot empty their bladder is called clean intermittent catheterization (CIC) which is when a patient intermittently places a catheter into the bladder themselves, several times daily. Another manifestation of a chronically obstructed bladder may be overflow incontinence where the bladder is always full and any additional urine leaks out against the patient’s desire. A large, obstructing prostate can also cause hooking or kinking or the ureters, the tubes coming down from the kidneys, which makes it difficult to perform surgery if a patient develops kidney stones.

Medical management of BPH:

There are many medications currently on the market for the treatment of BPH. There are two primary classes of medications: alpha-blockers and 5α-reductase inhibitors.

The alpha blockers are designed to block a specific type of receptor in prostatic smooth muscle. This is believed to allow the muscle to relax, thereby opening up the prostatic urethra and allowing for better urine flow. The most common medications in this class which are used today include:

Terazosin (Hytrin)

Doxazosin (Cardura)

Tamsulosin (Flomax)

Alfuzosin (Uroxatral)

The primary side effect with all of these medications is a decrease in blood pressure which can cause dizziness or lightheadedness. Terazosin and doxazosin can have more systemic effects so are often started at a low dose and then increased over several days to the recommended daily dose. Tamsulosin and alfuzosin can be started at the recommended treatment dose. Another possible side effect is either decreased ejaculation or retrograde ejaculation which is when the seminal fluid goes back into the bladder during ejaculation instead of out the penis. This effect is reversible if the medication is discontinued. Erectile function and sensation during sexual activity is not affected and it is not clinically significant unless there is a desire to have children because the semen will not go into the partner’s vagina but instead into the patient’s bladder. The same receptors that are blocked by the above medications can be excited by common medications used for nasal congestion such as Sudafed. Patients with BPH must be cautious using these medications as they may be unable to urinate and require placement of a catheter.

The other main class of medications is the 5α-reductase inhibitors, which inhibit the conversion of testosterone to the more potent dihydrotestosterone (DHT) in the prostate. DHT is the primary hormone involved in the growth of the prostate in BPH and decreasing the levels of DHT thus causes the prostate to shrink in size. There are two drugs in this class which are in clinical use:

Finasteride (Proscar)

Dutasteride (Avodart)

These medications can decrease the size of the prostate by up to 30% or more in some men after about 6 months of treatment. Patients undergoing PSA screening for prostate cancer should be aware that both of these medications artificially reduce the PSA level by about half. Side effects of these two medications may include decrease in libido, erectile dysfunction, and decrease in seminal volume. This class of medications also takes 3 to 6 months of use for the full effect to be appreciated.

Many patients with bothersome urinary symptoms from BPH, especially those with larger prostates, benefit most from a combination of both an alpha-blocker and a 5α-reductase inhibitor. Multiple large studies have shown a greater improvement in symptoms and/or progression of BPH in patients taking this combination of medications compared with patients on either medication alone.[1-3]

Phytotherapy for BPH:
There are a variety of plant extracts that are available for the treatment of urinary symptoms. The most common of these is saw palmetto which is derived from the bark of the American dwarf palm tree (Serenoa repens). There have been many different studies on the effectiveness of saw palmetto, with conflicting results. However, in an article from the New England Journal of Medicine from 2006, there were no significant differences in symptoms between patients on saw palmetto and those on placebo. There are a variety of other less common plant extracts available in nutrition stores and often marketed as formulas for men’s health but the data on these products is questionable, at best, and as with many nutritional supplements, patients must be cautious about the purity of what they are buying.  

Other Medications for Urinary Symptoms

There has been a recent increase in the use of antimuscarinic medications in the treatment of bothersome urinary symptoms from BPH [4,5]. These medications have traditionally been used mainly for women who have overactive bladder. However, as mentioned earlier, BPH and bladder obstruction from BPH can cause changes to occur in the bladder. These changes may cause overactivity of the bladder which manifests as urinary frequency, urinary urgency, and occasional urge urinary incontinence where a patient is unable to control the urge to urinate and urine leaks out uncontrollably. Furthermore, symptoms of overactive bladder can occur in men with minimal prostatic enlargement and the anti-muscarinics may be particularly useful in these patients. There are a large number of these medications available and they include:

Ditropan (oxybutynin)

Detrol (tolterodine)

Vesicare (solifenacin)

Sanctura (trospium chloride)

Enablex (darifenacin)

The most common side effects of these medications include dry mouth, dry eyes, and constipation. These medications must also be used with caution in patients with glaucoma, Parkinson’s disease, and Alzheimer’s as it may exacerbate the symptoms of these conditions. These medications may be used in combination with either an alpha blocker, a 5α-reductase inhibitor, or both.

A more recent development in the treatment of bothersome urinary symptoms has been the use of phosphodiesterase inhibitors. These are medications that help relax the smooth muscle in the penis and are typically used for the treatment of erectile dysfunction. There are currently three medications available in this class:

Viagra (sildenafil)

Levitra (vardenafil)

Cialis (tadalafil)

There is some recent evidence that these medications may help with bothersome urinary symptoms from BPH as well.  

Surgical Management of BPH:

There are many different surgical options for the treatment of BPH ranging from procedures which can be performed in a physician’s office to surgery which requires inpatient hospital admission. The traditional gold standard for the treatment of BPH has been the transurethral resection of the prostate or TURP. This is an endoscopic procedure where a scope is placed into the urethra and the obstructing prostatic tissue is resected with a wire electrosurgical cutting loop. Figure 3 shows how the prostate looks from inside the urethra. Most growth occurs in the lateral prostatic lobes, however, some patients have a more central growth that protrudes into the bladder which is known as the median lobe. The enlarged prostatic tissue is resected from the bladder neck (where the bladder meets the prostate) to the level of the verumontanum which is where the ejaculatory ducts enter the urethra. Care is taken not to resect tissue distal to this verumontanum as this may result in incontinence. A TURP is performed under a general or regional anesthetic and usually lasts for about an hour. There are no skin incisions as the surgery is performed by placing a scope through the tip of the penis into the urethra. The TURP has durable, well studied efficacy, no incisions, and relatively few side effects if performed correctly. After a TURP, a catheter is often left in place, sometimes connected to bladder irrigation, for one to two days and the patient is kept in the hospital. There are new, less invasive therapies to consider as well as technical updates to the traditional TURP.

Figure 3: Typical endoscopic (cystoscopic) appearance of the prostatic lobes from inside the urethra. 

 

Transurethral needle ablation (TUNA) involves placing a needle into each lobe of the prostate and then radiofrequency is used to heat the prostatic tissue to induce tissue destruction and subsequent sloughing of the obstructing tissue. This procedure is relatively quick, but the long term outcomes may not be as good as some of the other procedures available. A similar procedure called interstitial laser coagulation can be performed with the Indigo® laser. Irritative symptoms such as urinary frequency and urgency are common with these treatments and may persist for weeks or months after treatment. The long term efficacy of these therapies are not as good as the traditional TURP.

Transurethral Microwave Therapy (TUMT) involves placement of a special catheter into the bladder that uses microwaves to cause prostate tissue destruction. It typically can be done with local anesthesia and/or IV sedation. Depending on the type of machine used, the treatment typically lasts for an hour or less. There is usually swelling of the prostate after the procedure so an indwelling catheter is left in the bladder after treatment. The duration the catheter remains in place varies by device used and physician preference but typically is 2-4 days. A list of some of the most common TUMT devices used in the United States is shown below:
Targis (Urologix; Minneapolis, Minn)

Prostatron (Urologix)

TherMatrx Dose-Optimized Thermotherapy system (AMS; Minnetonka, Minn)

Urowave (Dornier MedTech; Kennesaw, Ga)

Prolieve system (Boston Scientific; Natick, Mass)

ProstaLund CoreTherm (ProstaLund Operations AB; Lund, Sweden; marketed by ACMI)

As mentioned earlier, the standard TURP remains the standard by which other modalities are measured. A recent advancement in TURP technology is the use of a bipolar electrode. There are several companies that produce this device and it allows the surgery to be performed with saline irrigation which diminishes the chances of TUR syndrome which can occur with the traditional TURP. This occurs when the body absorbs the irrigation fluid and it can lead to abnormalities of sodium and potassium levels in the blood.

There are several laser surgeries which are used in the treatment of BPH. These are designed to mimic the traditional electrosurgical TURP but instead use a laser to vaporize the obstructing prostate tissue. These treatments usually have very little blood loss and often have a shorter duration of post-operative catheterization than TURP. The photoselective vaporization of the prostate (PVP) is performed with a device called the GreenLight laser (AMS; Minnetonka, MN) and the holmium laser ablation of the prostate or HoLAP (Lumenis) uses the holmium laser which is often used in the treatment of kidney stones. Both of these procedures use saline irrigation to reduce the risk of TUR syndrome and both vaporize the prostate tissue with minimal bleeding. The side effects of these laser procedures are similar to a traditional TURP and the heat of the laser can also cause transient bladder overactivity resulting in urinary frequency and urgency. Another laser procedure, called a laser enucleation of the prostate, has recently gained popularity as well and may have better long term success rates but is more difficult to perform than a laser ablation.

For patients with very large prostates, while some of the aforementioned procedures are still an option, the most effective surgery may be a simple open prostatectomy. This is the most invasive type of surgery for BPH and involves making a small abdominal incision and then removing the entire central portion of the prostate while leaving the prostatic capsule intact. This should not be confused with a radical prostatectomy which is performed for prostate cancer, and which requires the entire prostate to be removed. A simple prostatectomy does not damage the cavernous nerves which are responsible for erectile function so impotence is not a common complication of a simple prostatectomy.

The most common complication of any BPH surgery is bleeding. Even with the newer procedures, which do not have significant bleeding during the surgery, heavy lifting or straining can cause bleeding from the remaining prostate. To help avoid this risk, patients should be off any blood thinners, for one to two weeks before surgery if possible. The laser vaporization procedures can be performed with patients on anticoagulation but post-operative bleeding can still occur.

For patients who are not surgical candidates or for patients who have irreversible bladder dysfunction and are unable to urinate on their own, there are several options. Patients may either have an indwelling catheter left in the bladder through the urethra, or a catheter can be placed into the bladder from a small opening in the lower abdomen, which is called a suprapubic tube. These catheters need to be changed every four to six weeks. Alternatively, patients may perform clean intermittent catheterization to empty the bladder and this is typically done every four to six hours to keep the bladder volumes to around 400 mL or less.

Can I still get prostate cancer after BPH surgery?

After any surgical treatment for BPH, there is a possibility of developing prostate cancer. The portion of the prostate that typically can develop cancer is the peripheral zone and this is the area that is left intact. Occasional, prostate cancer can be diagnosed in the prostatic tissue from a TURP or simple prostatectomy and if that is the case, further treatment is typically required to treat the prostate cancer. After most surgical procedures for BPH, the PSA level will likely decrease as the PSA is also correlated with the size of the prostate so with less prostate tissue, the PSA goes down.

The bottom line on BPH

BPH is very common in aging men and it has a large spectrum of symptoms and presentations.  Once the diagnosis is made, there are multiple medical and surgical treatments available and it is important to discuss the risks, benefits, and alternatives of any treatment with your doctor.

Other Resources:

American Urological Association  http://www.auanet.org/guidelines/patient_guides/bph_guide_2003.pdf

Kirkby RS, McConnell JD, Fitzpatrick JM, Roehrborn CG, and Boyle P. Textbook of Benign Prostatic Hyperplasia.  Informa Healthcare, 2004.

 

References

 

1.  Lepor H, Williford WO, Barry MJ, et al:  The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia.  Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group.  N Engl J Med 1996; 335:533-539.
2. McConnell JD, Roehrborn CG, Bautista OM, et al.  The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia.  N Engl J Med 2003;349;2387-2398.
3. Roehrborn CG, Siami P, Barkin J, et al.  The effects of Dutasteride, Tamsulosin and combination therapy on lower urinary tract symptoms in men with benighn prostatic hyperplasia and prostatic enlargement: 2-year results from the CombAT study.  J Urol 2008;179:616-621.
4. Chapple CR, Roehrborn CG: A shifted paradigm for the further understanding, evaluation, and treatment of lower urinary tract symptoms in men: focus on the bladder.  Eur Urol 2006;49:651-659.
5. Kaplan SA, Roehrborn CG, Dmochowski R,  et al.  Tolterodine extended release improves overactive bladder symptoms in men with overactive bladder and nocturia.  Urology 2006;68:328-332.