Benign prostatic hypertrophy

Benign prostatic hypertrophy

Walter M. O’Brien

Benign prostatic hypertrophy is one of the most common diseases affecting middle-aged and older men. Transurethral resection of the prostate (TURP) is the 10th most frequently performed operative procedure. Each year, an estimated 400,000 men undergo TURP for management of problems related to benign prostatic hypertrophy. [1] This article reviews current approaches to the management of patients with this disease.

Pathophysiology

The prostate gland sits on top of the urogenital diaphragm and beneath the bladder (Figure 1). It produces a portion of the seminal fluid and accounts for about 15 percent of the volume of ejaculate. The prostate is primarily involved in reproduction, but it may also provide some protection against urinary tract infection.

The prostate enlarges rapidly at puberty and then remains a constant size until about age 45. [2] At that time, the gland undergoes benign enlargement (Figure 2), or it atrophies. Hyperplasia of both epithelial and stromal elements produces the changes of benign prostatic hypertrophy.

Although the etiology of the hyperplasia in benign prostatic hypertrophy is unknown, it is clear that the testes and the aging process both play some role. However, their exact roles (such as changes in the testosterone and estrogen balance) have not yet been defined.

The testes must be present for the prostate to enlarge. Benign prostatic hypertrophy does not occur in men who were castrated before puberty, and established disease may regress following castration.

Benign prostatic hypertrophy does not occur before age 45; however, by 80 years of age, approximately 75 percent of men have the disease. By age 75, between 10 and 25 percent of men require some form of intervention for one of the complications of benign prostatic hypertorphy. [2]

An enlarged prostate does not cause problems unless it obstructs the outflow of urine from the bladder. As the gland enlarges, it may encroach on the urethral lumen, causing resistance to the outflow of urine from the bladder. In response to increased resistance, the detrusor muscle undergoes hypertrophy (Figure 3). Urinary retention occurs when the bladder muscle can no longer generate enough pressure to overcome the increased outlet resistance.

Clinical Presentation

Bladder outlet obstruction secondary to benign prostatic hypertrophy produces obstructive voiding symptoms. These symptoms may include hesitancy (difficulty in starting the urinary stream), decreased force of the urinary stream, terminal dribbling, postvoid fullness (feeling of fullness persisting after urination) and double voiding (need to urinate again five to 10 minutes after voiding). Other causes of bladder outlet obstruction include bladder neck contracture, urethral stricture, prostatic carcinoma and phimosis.

As a result of bladder outlet obstruction, the detrusor muscle undergoes hypertrophy, and irritative voiding symptoms develop. The thickened, hypertrophic bladder muscle is more irritable and more likely to contract. Irritative voiding symptoms include frequency, urgency, dysuria and nocturia. These symptoms may also be caused by infection, neurogenic bladder, distal ureteral stone and cystitis. The presence of irritative voiding symptoms in the absence of obstructive voiding symptoms suggests a disease other than benign prostatic hypertrophy. In such cases, more complete urologic evaluation is warranted.

The degree of difficulty caused by benign prostatic hypertrophy can be quantified using an objective symptom assessment score, such as that formulated by Boyarsky and co-workers. [3] This assessment has been applied in clinical trials to evaluate the outcome of intervention for the disease. A simplified version of this scoring system, as presented by Klein, [4] is useful for evaluating individual patients (Figure 4). Use of such a symptom assessment before and after treatment provides a good indication of the degree of improvement following treatment. There is no absolute score that indicates the need for intervention. However, a low symptom score favors postponing surgical intervention for benign prostatic hypertrophy.

Diagnosis

Diagnostic tools for assessing benign prostatic hypertrophy include the physical examination, cystoscopy, intravenous pyelography and urodynamic studies, as well as transrectal prostatic ultrasonography. [5] Typically, an enlarged prostate is felt on rectal examination. However, the size of the gland on rectal examination does not correlative with the degree of bladder outlet obstruction. A palpably small gland may produce significant bladder outlet obstruction. A palpably small gland may produce significant bladder outlet obstruction if the enlarged portion projects around the urethra. Alternatively, a palpably large gland may produce little or no bladder outlet obstruction if the gland does not encroach on the urethra.

If a large benign gland is felt rectally, but the symptoms are minimal and there is no evidence of bladder or renal compromise, surgical intervention is not needed. Digital examination of the prostate may disclose changes that suggest prostatic cancer. [TABULAR DATA OMITTED]

If malignancy is suspected, evaluation with needle biopsy should be performed.

Intravenous Pyelography

Intravenous pyelography can determine the degree of intravesical extension of the prostate and can, at times, help estimate the size of the prostate. In addition, the study may demonstrate thickening of the bladder wall or a large postvoid residual. “J hooking” of the ureters may be present due to distortion of the ureterovesical anatomy by the enlarged prostate (Figure 5). An intravenous pyelogram may also show dilatation of the ureters and the renal pelvis, suggesting impending renal compromise.

Although intravenous pyelography was once performed routinely to evaluate patients with benign prostatic hypertrophy, many physicians now believe that it is not required. Instead, renal ultrasonography can be performed to rule out hydronephrosis, thus avoiding the potential complications associated with the use of iodinated contrast medium.

Cystoscopy

Cystoscopy permits direct visual assessment of obstruction of the urethral lumen by the enlarged prostate. The presence of trabeculation, which represents bladder muscle hypertrophy, suggests bladder outlet obstruction (Figure 6).

Cystoscopy is usually performed in the office under local anesthesia. Both rigid and flexible cystoscopes are available. Flexible cystoscopy generally produces less patient discomfort. Before cystoscopy is performed, the patient is asked to void. The postvoid residual is measured once the cystoscope is advanced into the bladder. An elevated postvoid residual shows ineffective bladder emptying.

URODYNAMIC STUDIES

Urodynamic studies may include both a flow study and a cystometrogram. A flow study measures the rate of urine flow and can document decreased force of the urinary stream. A cystometrogram can be used to assess detrusor muscle function and to rule out a neurogenic bladder.

The value of urodynamic assessment in the evaluation of patients with benign prostatic hypertrophy is controversial. Urodynamic improvement and clinical improvement do not always correlate, and some men who have significant improvement in urinary flow rate have little or no symptomatic improvement. [6] Some urologists recommend that urodynamic studies be performed in every patient with benign prostatic hypertrophy, but others believe these studies should be reserved for more complicated cases. Urinary flow rates may be important in selecting patients who are likely to benefit from balloon dilatation of the prostate.

TRANSRECTAL PROSTATIC

ULTRASONOGRAPHY

Transrectal prostatic ultrasonography is being increasingly used to study the

TABLE 1

Therapeutic Options for the Management

of Benign Prostatic Hypertrophy

Surgical

Transurethral resection of the prostate

Open surgery

Nonsurgical

Catheter drainage

Balloon dilatation

Stents

Pharmacologic/hormonal

Alpha-adrenergic blockers

Antiandrogens

Analogs of gonadotropin-releasing hormone

5-Alpha-reductase inhibitors

Estrogen

Medical castration

prostate. [5] This technique can be useful for estimating the size of the prostate. Although the study can also identify asymptomatic prostatic carcinoma, its sensitivity and specificity for detecting cancer are too low to warrant its use for routine screening.

Presently, the most apprpriate uses of transrectal prostatic ultrasonography appear to be to assist with biopsy and, for patients with known prostatic cancer, to evaluate the anatomic extent of disease and monitor the response to therapy. At this time, transrectal prostatic ultrasonography is not recommended for screening patients with benign prostatic hypertrophy to detect occult prostatic carcinoma.

Treatment

Indications for the treatment of benign prostatic hypertrophy include urinary retention, hydronephrosis and secondary azotemia, severe hematuria, recurrent infection, bladder stone formation and troublesome symptoms. [1] The most common reason for intervention is the occurrence of troublesome symptoms. The degree of symptoms that prompts a patient to request intervention depends on the individual.

NONSURGICAL MANAGEMENT

Other than surgical resection or catheter drainage, several types of intervention are available [7] (Table 1). Pharmacologic agents that may be effective in the management of benign prostatic hypertrophy include alpha-adrenergic blockers, hormonal agents and antiandrogens.

The smooth muscle tone of the prostatic urethra and capsule is mediated through alpha-adrenergic receptors. Selective alpha [1] blockade can alleviate the symptoms of benign prostatic hypertrophy. Phenoxybenzamine (Dibenzyline), a nonspecific alpha-adrenergic blocker, has been used to alleviate the symptoms of benign protatic hypertrophy, improve urinary flow rates and reduce residual urine volume. [8] However, the frequent occurrence of side effects, including fatigue and dizziness, as well as concerns about potential carcinogenicity, have limited the use of phenoxybenzamine. Prazosin (Minipress), a selective alpha [1] blocker, has produced similar results, [9] with minimal side effects and without the concern for carcinogenicity.

Recently, terazosin (Hytrin), a longacting alpha, blocker, has been approved for use as an antihypertensive agent. Terazosin has produced significant improvement in obstructive symptoms and urinary flow rates. [10] However, orthostatic hypotension may occur, and the long-term effects of this agent are unknown. The usual dosage of terazosin is 1 or 2 mg orally once daily; however, to achieve the desired results, dosages of 5 to 10 mg per day have been necessary in some men.

Hormonal therapy can cause regression of established benign prostatic hypertrophy. [7] Castration causes shrinkage of the hyperthrophic epithelium but does not affect the stroma; therefore, the results of castration are unpredictable. Hormonal manipulation with estrogen may be effective, but it can produce unwanted side effects, such as gynecomastia, impotence and an increased risk of cardiovascular and thromboembolic disease.

Analogs of gonadotropin-releasing hormone (GnRH), such as leuprolide (Lupron), and antiandrogens, such as flutamide (Eulexin), can cause regression of an enlarged prostate. However, these agents are expensive, they impair libido and they can also produce impotence. Furthermore, once these medications are stopped, the changes of benign prostatic hypertrophy return. GnRH analogs and antiandrogens may be useful in select cases; for example, their use may avoid the need for catheterization in patients who are not candidates for surgery because of poor health or short life expectancy.

Future research will be directed at the development of MK-906 (Proscar), which inhibits the activity of 5-alpha-reductase, the enzyme that converts testosterone to dihydrotestosterone. [11,12] Limiting the amount of dihydrotesterone appears to decrease the size of the prostate without affecting libido or erectile function.

Recently, balloon dilatation of the prostatic urethra has been introduced as a treatment option for managing the symptoms of benign prostatic hypertrophy (Figure 7). Using a high-pressure balloon system that dilates the prostatic urethra to 75 Fr, Klein and associates [13] achieved successful improvement in the symptoms of 76 percent of patients after one year of follow-up. The long-term efficacy of this procedure is not yet known.

Balloon dilatation is less invasive and less costly than transurethral prostatectomy, and it is associated with a shorter recovery period. This form of treatment appears to be most effective in patients with mild obstruction. If should not be used in patients with advanced obstructive symptoms, very large prostates, enlarged middle lobes or prostatic cancer. The exact role of balloon dilatation remains to be defined, but it will probably play an increasingly important role in the management of benign prostatic hypertrophy.

SURGICAL MANAGEMENT

Surgical intervention remains the primary treatment for benign prostatic hypertrophy. Choices of surgical intervention include open surgery and TURP (Figure 8). Open surgical approaches include suprapubic, retropubic and perineal techniques. In any surgical treatment for benign prostatic hypertrophy, only the enlarged portion of the prostate is removed. Since the entire gland is not removed, the patient is still at the same risk as all men for the development of prostatic cancer.

Indications for open surgical removal of the prostate include a gland that is too large for TURP, a co-existing bladder stone and inability to place the patient in the dorsolithotomy position, usually secondary to ankylosis of the hips. The size of a gland that is too large for TURP depends on the individual surgeon.

One of the complications of TURP is the absorption of irrigation fluid, which can lead to volume overload and dilutional hyponatremia. This post-TURP syndrome is more likely to occur after a long period of resection or in vascular glands. The general rule of thumb for the urologist is to limit resection time to one hour. Glands that cannot be resected in that time should be removed through open surgery. Open surgery has complication rates similar to those for TURP. However, the postoperative recovery for open surgery is usually longer, and a catheter must be left in place for seven to 10 days.

In more than 90 percent of cases, surgical relief of bladder outlet obstruction secondary to benign prostatic hypertrophy can be achieved with TURP. The procedure is performed with a resectoscope, which is inserted through the urethra and into the bladder. The loop of the resectoscope is used to cut away the enlarged portion of the prostate under direct vision. An electric current directed through the loop cuts the prostatic tissue. The loop can also cauterize blood vessels to achieve hemostasis. To keep the field of vision clear, irrigation fluid is used to wash the resected chips into the bladder. All adenoma is resected down to the level of the true prostate, referred to as the prostatic capsule.

At the conclusion of resection, all chips are evacuated from the bladder, and a catheter is inserted. Resected tissue is examined histologically. Incidental carcinoma of the prostate is found in about 10 percent of patients who undergo TURP. If

TABLE 3

Complications of Transurethral

Resection of the Prostate

Dilutional hyponatremia

Bleeding

Infection

Incontinence

Impotence

Urethral stricture

Bladder neck contracture

Systemic complications

Deep venous thrombosis

Myocardial infarction

Other complications of general anesthesia

and surgery

prostatic cancer is found, subsequent management depends on the stage of the disease.

During resection, blood vessels that are cut open absorb irrigating fluid directly into the vascular system, possibly causing fluid overload and dilutional hyponatremia. If resection lasts longer than planned or if major venous vessels are entered, it is usually best to check serum electrolyte levels postoperatively. Continous bladder irrigation with normal saline is typically administered for the first 24 hours (or longer) postoperatively, until the urine is clear. The catheter is left in place for two to five days.

Complications of TURP include bleeding, infection, incontinence and impotence [14] (Table 2). Bleeding can occur because of coagulation defects, the most common of which is impaired platelet function secondary to aspirin or nonsteroidal anti-inflammatory drug use. These medications should be stopped two weeks before surgery. Infectious complications can be minimized by making sure that the urine culture is sterile prior to surgery. The role of prophylactic antibiotics is undefined.

Rare systemic complications of TURP include those associated with any form of surgery, such as cardiovascular events, deep venous thrombosis and pulmonary embolism. Long-term complications include urethral stricture or contracture of the bladder neck with scar tissue. Both of these cause recurrent bladder outlet obstruction and may require a second operative procedure for management. The mortality rate associated with TURP is 0.2 percent.

Incontinence, a rare but feared complication of TURP, is secondary to injury of the external sphincter. Impotence occurs in about 5 percent of cases and is probably the result of injury to the nerves responsible for erection. Retrograde ejaculation, which occurs in most patients who undergo TURP, is the result of resection of the adenoma at the level of the bladder neck. With retrograde ejaculation, a man’s sense of orgasm is not diminished, but he is usually sterile.

In approximately 85 percent of patients undergoing prostatectomy, bladder outlet obstruction is relieved and voiding symptoms improve. However, as many as 20 to 25 percent of patients who undergo TURP may at some time require a second procedure for the management of a urethral complication such as stricture or bladder neck contracture or for the resection of recurrent adenoma. [1]

Final Comment

Benign prostatic hypertrophy is a common condition that occurs in the majority of older men. With proper evaluation and appropriate intervention, most patients with this disease can be effectively treated. Selection of the most appropriate treatment for the individual patient is based on accurate assessment of symptoms and careful evaluation of the general medical condition of the patient.

REFERENCES

[1] Graversen PH, Gasser TC, Wasson JH, Hinman F Jr, Bruskewitz RC. Controversies about indications for transurethral resection of the prostate. J Urol 1989; 141:475-81.

[2] Walsh PC. Bening prostatic hyperplasia. In: Walsh PC, ed. Campbell’s Urology, 5th ed. Philadelphia: Saunders, 1986:1248-65.

[3] Boyarsky S, Jones G, Paulson DF, Prout GR Jr. A new look at bladder neck obstruction by the Food and Drug Administration regulators: guidelines for investigation of benign prostatic hypertrophy. Trans Am Assoc Genitourin Surg 1976; 68:29-32.

[4] Klein L. Balloon dilatation of the prostate: a urologist’s perspective. Uroplasty Seminar, Washington, D.C., April 7, 1990.

[5] Waterhouse RL, Resnick MI. The use of transrectal prostatic ultrasonography in the evaluation of patients with prostatic carcinoma. J Urol 1989; 141:233-9.

[6] Lepor H, Rigaud G. The efficacy of transurethral resection of the prostate in men with moderate symptoms of prostatism. J Urol 1990; 143:533-7.

[7] Lepor H. Nonoperative management of benign prostatic hyperplasia. J Urol 1989; 141: 1283-9.

[8] Caine M, Pfau A, Perlberg S. The use of alpha-adrenergic blockers in benign prostatic obstruction. Br J Urol 1976; 48:255-63.

[9] Hedlund H, Andersson KE, Ek A. Effects of prazosin in patients with benign prostatic obstruction. J Urol 1983; 130:275-8.

[10] Dunzendorfer U. Clinical experience: symptomatic management of BPH with terazosin. Urology 1988; 32(6 Suppl):27-31.

[11] Wenderoth UK, George FW, Wilson JD. The effect of a 5 alpha-reductase inhibitor on androgen-mediated growth of the dog prostate. Endocrinology 1983; 113:569-73.

[12] McConnell JD. Medical management of benign prostatic hyperplasia with androgen suppression. Prostate 1990; 3(Suppl):49-59.

[13] Klein L, Perez-Marrero R, Bowers GW, Ludwig JJ, Herwig K. Transurethral cystoscopic balloon dilatation of the prostate. J Endourol 1990; 4:115-23.

[14] Mebust WK, Holtgrewe HL, Crockett AT, Peters PC. Transurethral prostatectomy; immediate and postoperative complications. A cooperative study of 13 participating institutions evaluating 3,885 patients. J Urol 1989; 141:243-7.

WALTER M. O’BRIEN, M.D. is clinical instructor in urology at Georgetown University Hospital in Washington, D.C., and is also in private practice in the metropolitan Washington area. A graduate of Jefferson Medical College of Thomas Jefferson University, Philadelphia, Dr. O’Brien recently completed a residency in urology at Georgetown University Hospital.

COPYRIGHT 1991 American Academy of Family Physicians

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