Benign Prostatic Hyperplasia (BPH)

1. Definition and Overview

• Robbins & Kumar Basic Pathology
• Goldman-Cecil Medicine

2. Anatomy of the Prostate

• Peripheral zone - largest; site of most prostate cancers
• Central zone - surrounds ejaculatory ducts
• Transition zone - surrounds the proximal urethra; site of BPH
• Anterior fibromuscular stroma

3. Epidemiology

• Histologic BPH develops in approximately 50% of men over age 50 and 90% of men in their 80s
• Of those with histologic BPH, approximately 50% develop clinically significant lower urinary tract symptoms (LUTS)
• BPH affects approximately 70% of males between ages 60-69
• LUTS prevalence increases linearly between ages 40 and 80
• Age is the single strongest risk factor
• Goldman-Cecil Medicine; Sabiston Textbook of Surgery

4. Pathogenesis

Hormonal Mechanism

1. Circulating testosterone is converted to DHT within prostatic stromal cells by the enzyme 5α-reductase type 2
2. DHT is 10x more potent than testosterone
3. DHT binds nuclear androgen receptors, regulating genes that support growth and survival of both prostatic epithelium and stromal cells
4. DHT-induced growth factors increase stromal cell proliferation and decrease epithelial cell apoptosis

Role of Estrogen

Bladder Outlet Obstruction Mechanism

• Directly obstructing urinary outflow (mechanical component)
• Increasing smooth muscle tone of the prostate and bladder neck (dynamic component)
• Triggering overactive detrusor function in response to obstruction, causing storage symptoms

• Robbins & Kumar; Goldman-Cecil Medicine

5. Pathology (Gross and Microscopic)

Gross Appearance

• Prostate weight increases 3- to 5-fold (60-100 g or more)
• BPH arises from the transition zone, compressing the urethra to a slit-like orifice
• Cross-section shows hyperplastic nodules that vary in color and consistency
• Nodules may be solid or contain cystic spaces (dilated glands)

Microscopic Appearance

• Variable proportions of proliferating glandular elements and fibromuscular stroma
• Hyperplastic glands are lined by two cell layers:
  • Inner: tall, columnar epithelial cells
  • Outer: flattened basal cells (KEY distinguishing feature from prostate carcinoma, which lacks basal cells)
• Glandular lumina often contain corpora amylacea (laminated proteinaceous secretory material)

6. Clinical Features

Symptoms - Classified into Three Categories

Complications of Chronic Obstruction

• Bladder hypertrophy and distension (trabeculation, diverticula)
• Residual urine - culture medium for bacteria
• Recurrent urinary tract infections
• Bladder calculi
• Hydronephrosis (bilateral) from chronic retention
• Acute urinary retention - a urologic emergency
• Chronic renal insufficiency from long-standing bilateral hydroureteronephrosis
• Hematuria

7. Diagnosis and Evaluation

History

• Symptom assessment using the International Prostate Symptom Score (IPSS)
• Medications review: diuretics, nasal decongestants, antihistamines can worsen symptoms
• Dietary factors: caffeine, alcohol, artificial sweeteners, fluid intake

Physical Examination

• Digital rectal examination (DRE) - assesses prostate size and nodularity; only the posterior half is palpable, giving an approximate estimate
• Abdominal examination - palpable bladder suggests retention
• Focused neurologic examination (mental status, lower extremity function, anal sphincter tone)

Laboratory Tests

• Urinalysis - screen for hematuria, UTI
• PSA - in appropriate patients (life expectancy >10 years); correlates with prostate volume and predicts symptom progression; 5α-reductase inhibitors reduce PSA by ~50%
• Serum creatinine - assess for renal insufficiency

Objective Urological Tests

• Uroflowmetry - measure maximum urinary flow rate
• Post-void residual (PVR) ultrasound
• Prostate volume by transabdominal or transrectal ultrasound
• Cystoscopy - if hematuria is present or prior to minimally invasive procedures
• Urodynamic studies - if diagnosis is in question

Differential Diagnosis to Consider

• Prostate cancer
• Bladder cancer (especially with hematuria)
• Urethral stricture
• Bladder stones
• Neurogenic bladder (Parkinson disease, multiple sclerosis, diabetes)
• Overactive bladder

8. Treatment

Step 1: Watchful Waiting / Behavioral Therapy

• For IPSS ≤ 7 (mild symptoms) or moderately symptomatic but not bothered
• Measures include: fluid restriction, timed voiding, double voiding, caffeine/alcohol reduction

Step 2: Medical Therapy

A. α1-Adrenergic Receptor Blockers (First-Line)

• Mechanism: relax smooth muscle in bladder neck and prostate, reducing outflow resistance
• Selective α1a subtype blockers preferred (prostate-specific)
• Examples: tamsulosin, alfuzosin, silodosin, terazosin, doxazosin
• Onset of action: rapid (days)
• Side effects: orthostatic hypotension, retrograde ejaculation, rhinitis, floppy iris syndrome (discontinue before cataract surgery)

B. 5α-Reductase Inhibitors (5-ARIs)

• Mechanism: block conversion of testosterone → DHT, reducing prostate glandular volume
• Examples: finasteride (5-ARI type 2), dutasteride (dual 5-ARI types 1 and 2; evidence suggests dutasteride preferred)
• Onset: slow (months for full effect)
• Reduces prostate volume, episodes of acute urinary retention, and need for surgery
• Most effective for larger prostates (>30 mL)
• Side effects: erectile dysfunction, reduced libido, decreased ejaculate volume
• Reduces PSA by ~50% (must be accounted for in cancer screening)

C. Phosphodiesterase Type 5 Inhibitors (PDE5i)

• Example: tadalafil (daily dosing approved for BPH)
• Useful in patients who also have erectile dysfunction
• Can be used as initial therapy in such patients

D. Antimuscarinics

• Target muscarinic receptors in the bladder to reduce overactivity
• Examples: tolterodine, solifenacin, fesoterodine
• Used for storage symptoms/overactive bladder component

E. β3-Agonists

• Examples: mirabegron, vibegron
• Stimulate β3 receptors → smooth muscle relaxation in bladder wall
• Alternative to antimuscarinics for storage symptoms

Combination Therapy

• Alpha blocker + 5-ARI = best documented combination (superior to either alone)
• Alpha blocker + PDE5i = efficacious
• Tamsulosin + dutasteride + antimuscarinic/β3-agonist for refractory OAB symptoms
• Saw palmetto: not recommended - randomized trials show no benefit at 12 months

Step 3: Surgical Intervention

• Acute urinary retention
• Recurrent UTI
• Recurrent hematuria refractory to 5-ARI
• Bladder calculi
• Azotemia / renal insufficiency
• Failure or inadequacy of medical therapy

Surgical Options by Prostate Size

Key Surgical Procedures

• Electrosurgical resection of transition zone tissue
• Bipolar TURP (with saline irrigation) has replaced monopolar in many centers - eliminates dilutional hyponatremia from glycine absorption (TURP syndrome)
• Complications: persistent bleeding, UTI, urinary incontinence, urethral stricture, retrograde ejaculation

• HoLEP (Holmium Laser Enucleation) - effective for all prostate sizes; lower bleeding risk, preserves ejaculatory function better
• ThuLEP (Thulium Laser Enucleation) - similar outcomes to HoLEP
• PVP (Photoselective Vaporization of the Prostate, "GreenLight") - vaporization rather than resection

• PUL (Prostatic Urethral Lift, Urolift): mechanical implants open prostatic parenchyma - limited to prostate <80 g with no significant middle lobe; preserves ejaculatory/erectile function
• WVTT (Water Vapor Thermal Therapy, Rezum): radiofrequency-induced water vapor causes coagulation necrosis; prostate 30-80 mL; also ejaculation-preserving
• RWT (Rezum Water Therapy): prostate 30-80 mL
• TUIF/TUIP (Transurethral Incision of Prostate): for small prostates ≤30 mL
• Prostatic artery embolization (PAE): efficacy and safety data limited; option in selected patients
• Sabiston Textbook of Surgery; Goldman-Cecil Medicine (AUA 2023 guidelines)

9. PSA in BPH

• PSA levels correlate with prostate volume even without cancer
• PSA and prostate volume generally predict worsening of symptoms over time
• 5α-reductase inhibitors reduce PSA by ~50%; when interpreting PSA, double the measured value in patients on these medications
• Hematuria in BPH requires cystoscopy to rule out bladder cancer

10. BPH in Special Situations

• Estimated 3-year incidence of BPH post-transplant: ~9.7%
• Associated with increased UTI risk and graft loss
• Prophylactic alpha-blocker and constipation management before Foley removal recommended
• TURP is safe ≥3 weeks post-transplant; avoid in first 2 weeks and in the presence of a ureteral stent (associated with sepsis and death)
• Campbell-Walsh-Wein Urology

Summary Table