Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is characterized by progressive enlargement of the prostate gland resulting in bladder outlet obstruction and increasingly difficult voiding. It is a disease of the elderly, rarely affecting males younger than age 40. The mean age at which patients develop symptoms is between 60 and 65 years.

PATHOGENESIS

The prostate consists of three distinct zones: an outer peripheral zone, a central zone, and a periurethral transition zone. BPH develops in the transition zone, whereas prostate cancer usually arises in the peripheral zone. Clinically, the prostate is still often considered to have five lobes: anterior, posterior, median, and two lateral lobes.

The cause of BPH remains unclear; however, its relationship to aging and the testes is well documented. Most current theories on the etiology of BPH focus on an increased sensitivity to androgens and a decreased rate of cell death. Direct stromal-epithelial interaction under hormonal control appears to be essential to the process.

Prostate growth and development are under the influence of the male hormone, testosterone, and its more active metabolite dihydrotestosterone (DHT). Testosterone, which is produced primarily by the testes under control of the hypothalamic-pituitary axis, is converted to DHT by the enzyme 5-α-reductase. DHT is the major intracellular androgen and is believed to be responsible for the maintenance of BPH. With advancing age, Leydig cell testosterone production decreases, resulting in a relative excess of estrogens. Estrogens have been demonstrated to cause increased nuclear accumulation of DHT receptors and to result in a net increased formation of DHT within the prostate. DHT stimulation results in increased production of epidermal growth factor (EGF), whereas other factors cause a reduction in programmed cell death or apoptosis, presumably as a result of transforming growth factor-β (TGF-β). BPH is believed to result from the imbalance of stromal and epithelial hyperplasia caused by EGF in the face of reduced apoptosis caused by TGF-β.

PATHOPHYSIOLOGY

Prostatic hyperplasia would be of no importance were it not for the consequent bladder outlet obstruction. The pathophysiology of bladder outlet obstruction has three components: a mechanical component, a dynamic component, and the detrusor response.

Mechanical Obstruction

With progressive prostatic growth, patients will present clinically with lateral and/or median lobe enlargement. As prostatic enlargement encroaches on the urethra, urinary outflow obstruction occurs. The mechanical component of obstruction is a direct result of this enlarging mass of tissue and its ability to increase outlet resistance and obstruct urine flow. The outer prostate glands proper become compressed against the prostatic capsule during this growth, resulting in a thick pseudocapsule referred to as the surgical capsule.

The anatomic configuration of the prostate can have an important effect on the degree of obstruction produced. Some patients can develop primarily median lobe hyperplasia or just a hyperplastic posterior commissure of the bladder neck, which is commonly referred to as a median bar. In these settings, relatively small degrees of hyperplasia can result in major impairment of flow. The enlarging mass of hyperplastic tissue and the favorable or unfavorable anatomic configuration it takes are usually the major components of prostatic obstruction. The overall size of the prostate in BPH often correlates poorly with the degree of obstructive symptoms but can be predictive of the success or failure of various treatment modalities.

Dynamic Obstruction—Prostate Smooth Muscle

The dynamic component of prostatic obstruction is related to the tone of the prostatic smooth muscle fibers. Smooth muscle fibers constitute a significant component of the true capsule, intervening stroma within the prostate, periurethral area, and the bladder neck.

Smooth muscle fibers of the prostate and bladder neck are richly innervated by adrenergic fibers of the sympathetic nervous system and α₁-type receptors. Specifically α_1A-subtype receptors predominate within the prostate, whereas α_1B-subtype receptors mediate peripheral vasoconstriction. The baseline tone of the sympathetic autonomic nervous system is believed to modulate these smooth muscle fibers and, thus, prostatic urethral resistance.
Medications containing adrenergic agonists (e.g., nasal decongestants) can result in worsening outlet obstruction or urinary retention. α-Adrenergic blockers are effectively used to relax prostatic smooth muscle and thus lower bladder outlet resistance.

Detrusor Response

As outlet resistance increases, the bladder responds by increasing its force of contraction. By developing increased intravesical voiding pressures, the bladder can maintain flow and the appearance of normalcy. The added work to overcome outlet resistance results in detrusor hypertrophy, hyperplasia, and deposition of collagen within the bladder wall. This results in what is seen at cystoscopy as trabeculation, cellules, and diverticuli. With thickening of the bladder wall, its normal elasticity is lost and compliance decreases. The loss of compliance results in a decrease in the functional capacity of the bladder, i.e., increased intravesical pressure for a given volume. These bladder changes also cause the development of detrusor instability, or loss of normal control over the reflex detrusor response.

Early in the course of obstruction, the bladder is able to compensate. However, with progression, irritative voiding symptoms (e.g., frequency, urgency, nocturia, and urgency incontinence) result. It is the irritative voiding symptoms that are most responsible for the patient’s complaints. Untreated, this process can progress to severe bladder decompensation and dilatation, ureterovesical obstruction and hydroureteronephrosis, and, ultimately, renal insufficiency.