Benign Prostatic Hyperplasia

Introduction

• Benign prostatic hyperplasia (BPH), a nearly ubiquitous condition, is the most common benign neoplasm of American men.
• Three types of prostate gland tissue: epithelial or glandular, stromal or smooth muscle, and capsule. Both stromal tissue and capsule are embedded with α1 -adrenergic receptors.
• The precise pathophysiologic mechanisms that cause BPH are not clear. Both intraprostatic dihydrotestosterone (DHT) and type II 5α-reductase are thought to be involved.
• BPH commonly results from both static (gradual enlargement of the prostate) and dynamic (agents or situations that increase α-adrenergic tone and constrict the gland’s smooth muscle) factors. Examples of drugs that can exacerbate symptoms include testosterone, α-adrenergic agonists (e.g., decongestants), and those with significant anticholinergic effects (e.g., antihistamines, phenothiazines, tricyclic anti- depressants, antispasmodics, and antiparkinsonian agents).

Clinical Presentation

• Patients present with a variety of signs and symptoms categorized as obstructive or irritative. Symptoms vary over time.
• Obstructive signs and symptoms result when dynamic and/or static factors reduce bladder emptying. Patients experience urinary hesitancy, urine dribbles out of the penis, and the bladder feels full even after voiding.
• Irritative signs and symptoms are common and result from long-standing obstruction at the bladder neck. Patients experience urinary frequency, urgency, and nocturia.
• BPH progression may produce complications including chronic kidney disease, gross hematuria, urinary incontinence, recurrent urinary tract infection, bladder diverticula, and bladder stones.

Diagnosis

• Includes careful medical history, physical examination, objective measures of bladder emptying (e.g., peak and average urinary flow rate and postvoid residual [PVR] urine volume), and laboratory tests (e.g., urinalysis and prostate-specific antigen [PSA]).
• On digital rectal examination, the prostate is usually but not always enlarged (>20 g), soft, smooth, and symmetric.

Treatment

• Goals of Treatment: The goals are to control symptoms, prevent progression of complications, and delay need for surgical intervention.
• Management options include watchful waiting, drug therapy, and surgical intervention. The choice depends on severity of signs and symptoms.
• Watchful waiting is appropriate for patients with mild disease. Patients are reassessed at 6-to-12-month intervals and educated about behavior modification, such as fluid restriction before bedtime, avoiding caffeine and alcohol, frequent emptying of the bladder, and avoiding drugs that exacerbate symptoms.

Pharmacologic therapy

• Initiate therapy with an α1 -adrenergic antagonist for faster onset of symptom relief. Select a 5α-reductase inhibitor in patients with a prostate gland more than 40 g. Consider combination therapy for symptomatic patients with a prostate gland more than 40 g and PSA of 1.4 ng/mL or more (1.4 mcg/L).
• Consider monotherapy with a phosphodiesterase inhibitor or use in combination with an α-adrenergic antagonist when erectile dysfunction and BPH are present.

α-Adrenergic Antagonists

• Prazosin, terazosin, doxazosin, and alfuzosin are second-generation α1 -adrenergic antagonists. They antagonize peripheral vascular α1 -adrenergic receptors in addition to those in the prostate
• Slowly titrate to a maintenance dose at bedtime to minimize orthostatic hypotension and first-dose syncope with immediate-release formulations of terazosin and doxazosin. Sample titration schedules for terazosin include:

Terazosin Slow Terazosin Quicker

Days 1–3: 1 mg at bedtime Days 1–3: 1 mg at bedtime Days 4–14: 2 mg at bedtime Days 4–14: 2 mg at bedtime Weeks 2–6: 5 mg at bedtime Weeks 2–3: 5 mg at bedtime Weeks 7 and on: 10 mg at bedtime Weeks 4 and on: 10 mg at bedtime

• Tamsulosin and silodosin, third-generation α1 -adrenergic antagonists, are selective for prostatic α1A-receptors. Therefore, they do not cause peripheral vascular smooth muscle relaxation and associated hypotension.

Phosphodiesterase Inhibitors

• Tadalafil 5 mg daily improves voiding symptoms but does not increase urinary flow rate or reduce PVR urine volume. Combination therapy with α-adrenergic antagonist results in significant improvement in lower urinary tract symptoms, increased urinary flow rates, and decreased PVR volume.

Anticholinergic Agents

• Addition of oxybutynin and tolterodine to α-adrenergic antagonists relieves irritative voiding symptoms including urinary frequency, urgency, and nocturia. Start with lowest effective dose to determine tolerance of CNS adverse effects and dry mouth. Measure PVR urine volume before initiating treatment (should be less than 250 mL).
• If systemic anticholinergic adverse effects are poorly tolerated, consider transdermal or extended-release formulations or uroselective agents (e.g., darifenacin or solifenacin).

Surgical Intervention

• Prostatectomy, performed transurethrally or suprapubically, is the gold standard for treatment of patients with moderate or severe symptoms of BPH and for all patients with complications.
• Retrograde ejaculation complicates up to 75% of transurethral prostatectomy procedures. Other complications seen in 2% to 15% of patients are bleeding, urinary incontinence, and erectile dysfunction.