Benign prostatic hyperplasia (prostate enlargement)

Benign prostatic hyperplasia (prostate enlargement)

The majority of men who consult urologists do so because of some kind of impairment of the urinary flow. In the group under forty-five years of age, this is usually due to prostatitis, which is an inflammation—frequently an infection—of the prostate gland. In men over forty-five, the cause is often benign prostatic hyperplasia (BPH) brought about by an abnormal, but nonmalignant, proliferation of cells and tissues of the gland. Histologic evidence of BPH is found in more than 50 percent of sixty-year-old men and in 90 percent of men by age eighty-five. Eventually, urethral obstruc- tion leads to urinary retention, kidney damage, and infection. In advanced stages, surgical resection is the treatment of choice. In 1990, more than three hundred thousand operations were performed for BPH in the United States at a cost of more than two billion dollars.

To understand how medications may affect BPH, it is necessary to understand the mechanism that causes the condition. In the pros- tate, as is the case with many accessory sex organs, testosterone from the blood penetrates the prostatic cell by passive diffusion and is con- verted by the enzyme steroid 5 α-reductase to the more potent androgen,

Chapter four: Kidney, urinary tract, and prostate problems

69 dihydrotestosterone (DHT). The DHT binds to a specific receptor in the

cytoplasm and this DHT-receptor complex is transported to the nucleus, where it initiates ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) synthesis. This, in turn, results in protein synthesis, cell metabolism, and cell division.

In the normal growth process, when sex accessory organs reach a certain size, their further development is no longer influenced by testos- terone or DHT. However, four to six times the normal amount of DHT is found in the hyperplastic prostate. Apparently, this high concentration of the hormone results in increased growth of the gland in mature males, but the reason for its presence and the manner in which it leads to hyper- plasia are poorly understood.

In clinically significant BPH (enlarged prostate with clinical symp- toms), hyperplastic nodules develop in the periurethral zone of the pros- tate gland. As these nodules enlarge, they compress both the surrounding prostatic tissue and the urethra, leading to a mechanical obstruction of urine flow from the bladder. In addition to the mechanical obstruction, the smooth muscle of the prostate capsule and the proximal urethra, as

well as the trigone muscle of the bladder, are rich in α 1 -adrenergic recep- tors that create a dynamic component of obstruction that fluctuates with autonomic stimulation.

The most common treatment for BPH is partial prostatectomy; how- ever, in the past few years interest in nonsurgical therapy, including the use of drugs, has increased. Drug therapy can be considered in patients who do not have absolute indication for surgery or who are poor surgical risks, but at the present time it is generally not considered an alternative to surgery.

A second drug therapy approach is to use selective α 1 -receptor block- ers such as terazosin (Hytrin). Blocking the α 1 -adrenergic receptors relaxes the smooth muscles of the prostate, thereby decreasing tone and increasing urinary flow rates ( Figure 4.2 ). These drugs were originally developed for treating hypertension. Side effects occurring in 10–15 percent of patients include orthostatic hypotension, dizziness, tiredness, and headache. 53

Although herbal medicines are widely used to treat the early stages of BPH in Europe, it must be noted that OTC drug products that claim to treat BPH cannot be sold in the United States. The FDA has banned their sale for two reasons: (1) the agency has not received evidence proving their effectiveness, and (2) their use may delay proper medical treatment. 54

Substantial clinical evidence has now accumulated that makes the first reason for the FDA ban invalid, and two herbal medicines have received approval by German health authorities. 55 The second reason remains valid, and patients who have the obstructive and irritative symptoms of BPH should seek physician care because these symptoms may be caused

70 Tyler's herbs of choice: The therapeutic use of phytomedicinals

Finasteride

Stimulation Testosterone

α 1 -Adrenergic receptors α Steroid

1 -Adrenergic blockers

5α-reductase

(e.g., terazosin)

Dihydrotestoserone (DHT)

Increased contraction of smooth muscle

Increased prostatic cell growth (hyperplasia)

Dynamic obstruction Mechanical obstruction

Decreased urine flow

Figure 4.2 The mechanism of drug therapy in the treatment of benign prostatic hyperplasia (BPH).

by other conditions such as prostatic and bladder carcinomas, neurogenic bladder, and urinary tract infection.