Benign Prostatic Hyperplasia

See Also

Epidemiology

As of 2015, BPH affects 38 Million men in U.S. over age 30 years (25% of all U.S. men)
1. Moderate symptoms in >50%
2. More than one third seek medical management
Incidence of BPH increases with age
1. Men aged 60 years: 50%
2. Men aged 80 years: 88%
Incidence of symptomatic onset is related to ethnicity
1. African american men: Onset at age 60 years
2. Caucasian men: Onset at age 65 years

Pathophysiology

Prostate size increases with age
1. Birth: few grams
2. Age 20 to 55 years: 20-30 ml volume (normal)
3. Age over 55 years: Increased growth (>40 ml volume is considered large)
Prostatic Hyperplasia begins centrally (periurethral)
1. Prostatic Hyperplasia compresses Urethra
2. Results in urinary flow obstruction
Prostate growth is hormonally regulated
1. Testosterone converted to Dihydrotestosterone
2. Dihydrotestosterone stimulates Prostate growth
3. Estrogen also stimulates Prostate growth

Risk Factors
Provocative factors for Urinary Retention

See Medication Causes of Urinary Retention
Comorbid conditions associated with neurogenic Bladder
Post-operative pelvic floor Muscle spasm
1. Herniorrhaphy
2. Hydrocelectomy
3. Perirectal Abscess
4. Rectal Trauma or perineal Trauma
Factors Increasing Prostate Size and Obstructive Symptoms
1. Advanced Age (see epidemiology above)
2. Tobacco Smoking
3. Diabetes Mellitus
4. Hypertension
5. Obesity
6. Sedentary lifestyle
Conditions that may mimic BPH symptoms
1. Urinary Tract Infection
2. Overhydration
3. Caffeine, Alcohol and Diuretics
Comorbid conditions predisposing to non-BPH related Urinary Retention
1. Prior Urethral instrumentation
2. Nephrolithiasis

Symptoms

See International Prostate Symptom Score
Obstructive uropathy symptoms
1. Weak urine stream with decreased caliber
2. Hesitancy starting urine stream
3. Incomplete voiding Sensation
4. Urinary Retention
  1. Double voiding (returning to urinate shortly after)
  2. Straining to empty Bladder
5. Postvoid or terminal dribbling
Irritative symptoms
1. Dysuria
2. Urinary Frequency
3. Urinary urgency
Increased urine Residual Volume symptoms
1. Nocturia
2. Overflow Incontinence
3. Bladder palpable on exam
Symptoms suggestive of alternative cause
1. Fever
2. Gross Hematuria

Signs

Digital Rectal Exam
1. Findings suggestive of Prostate Cancer
  1. Asymmetry
  2. Induration
  3. Nodularity
  4. Diffuse firmness
2. Findings suggestive of Benign Prostatic Hyperplasia
  1. Symmetric prostatic enlargement
    1. Identifies Prostate enlargement >50 ml
  2. Smooth
  3. Firm but elastic
3. Findings suggestive of Prostatitis
  1. Prostate tenderness
  2. Fever
Abdominal and genitourinary exam
1. Suprapubic swelling of distended Bladder
2. Signs of Urethral Stricture
  1. Penile induration
  2. Penile nodularity
3. Balanoposthitis
  1. Meatal stenosis (Diabetes Mellitus)
Neurologic Exam (evaluate for neurogenic Bladder)
1. Motor Exam of lower extremities
2. Anal sphincter tone
3. Sensory Exam of perineum

Differential Diagnosis

Labs

Urinalysis (Urine Dipstick with urine microscopy)
1. Urinary Tract Infection
2. Hematuria
Prostate Specific Antigen (PSA)
1. NOT required for evaluation of lower urinary tract symptoms
2. Prostate Cancer
  1. AUA recommends if Life Expectancy >10 years
  2. See Prostate Specific Antigen (PSA) for Informed Consent discussion in obtaining PSA
3. Evaluate Prostate size (determines efficacy for 5a-Reductase Inhibitor)
  1. PSA >1.5 ng/ml is a proxy for an enlarged Prostate
Urine cytology
1. Consider if risk of Bladder Cancer
Renal Function Tests (Serum Creatinine and Blood Urea Nitrogen)
1. No longer recommended since BPH does not affect baseline renal disease risk
2. Previously recommended to assess for Postrenal Azotemia

Diagnostics

Urodynamics
1. See Urodynamics
2. Not recommended in the initial evaluation of BPH
  1. May be used later to guide management
Transabdominal Ultrasound for Post-Void Residual Urine
1. Normal residual urine <100 ml
2. Poor efficacy in identifying Bladder outlet obstruction
  1. Positive Predictive Value 63%
  2. Negative Predictive Value 52%
Transrectal Ultrasound (Prostate size evaluation)
1. More accurate than Digital Rectal Exam in estimating Prostate size
2. AUA recommends Ultrasound before 5-alpha reductase inhibitor use or surgery
  1. Poor evidence for outcome benefit (compared with Rectal Exam) before starting 5-alpha reductase inhibitors

Management
Conservative Measures for mild symptoms

Limit night-time water consumption
Weight loss (if Overweight)
Observe for complications with annual examination
Avoid provocative medications and substances
1. See risk factors above
2. Reduce Caffeine and Alcohol intake
3. Avoid Anticholinergics (e.g. Antihistamines, Oxybutynin)
Manage Constipation
Physical Therapy Measures
1. Pelvic Floor Exercise (Kegel Exercise)
2. Urethral milking
  1. Massage Urethra from behind the Scrotum toward the base of the penis

Management
Medications - First-Line

Indications
1. Benign Prostatic Hyperplasia Symptom Index 8 or higher
Alpha Adrenergic Antagonists (long-acting)
1. Efficacy
  1. Excellent, low cost, rapid onset first-line agents
  2. Decreases International Prostate Symptom Score (IPSS) 2 to 4 points
  3. Preferred over 5a-Reductase Inhibitors (Finasteride) as first-line Therapy
2. Selective agents (preferred, no Blood Pressure effect)
  1. Risk of ejaculatory dysfunction
    1. May decrease with every other day dosing (similar BPH efficacy)
  2. Tamsulosin (Flomax) 0.4 mg (up to 0.8 mg) orally daily (generic)
  3. Silodosin (Rapaflo) 8 mg orally daily
  4. Alfuzosin (Uroxatral) 10 mg orally daily (generic)
    1. Alfuzosin ER is least likely to cause ejaculatory dysfunction of the selective alpha agents
3. Non-Selective agents (Antihypertensives, risk of Dizziness, Orthostatic Hypotension, Fall Risk)
  1. Terazosin (Hytrin)
  2. Doxazosin (Cardura)
  3. Prazosin (Minipress) is not recommended due to lack of evidence
Phosphodiesterase 5 Inhibitors (PDE5 Inhibitor)
1. Indications
  1. First-line alternative to Alpha Adrenergic Antagonists
  2. Consider in patients with both BPH AND Erectile Dysfunction
  3. Avoid combining with Alpha Adrenergic Antagonists
    1. Risk of Hypotension (as well as Headache, myalgias) and low added benefit
2. Efficacy
  1. Similar efficacy to Alpha Adrenergic Antagonists
    1. Pattanaik (2018) Cochrane Database Syst Rev (11): CD010060 [PubMed]
    2. Rohrbough (2024) Am Fam Physician 109(1): 83-4 [PubMed]
  2. Improves symptom scores but not post-Residual Volume or max urine flow in metaanalysis
    1. Hatzimouratidis (2014) Ther Adv Urol 6(4): 135-47 +PMID: 25083163 [PubMed]
3. Medications
  1. Tadalafil (Cialis) 5 mg once daily

Management
Medications - Second-Line

Indications
1. Symptomatic BPH with Large Prostate size
2. Often combined with Alpha Adrenergic Antagonists
5a-Reductase Inhibitor (Testosterone conversion inhibitor)
1. Consider as adjunct to Alpha Adrenergic Antagonists (if not controlled after 4 to 12 weeks)
2. Efficacy
  1. See Finasteride
  2. Less effective than alpha blockade or surgery
  3. Decreases Prostate volume 15 to 25% in first 6 months
  4. Decreases BPH progression at 4 years and effects persist for 10 years
  5. Decreases risk of acute Urinary Retention and surgical intervention
  6. Decreases International Prostate Symptom Score (IPSS) 1 to 2 points
  7. Maximum effect not reached until 6-12 months after starting
  8. Most effective in men with large Prostate (>40 ml)
    1. Digital Rectal Exam or transrectal Ultrasound predicts size
    2. See PSA for estimating Prostate size
  9. Finasteride effective in reducing Gross Hematuria due to BPH (80%)
  10. Tachlind (2010) Cochrane Database Syst Rev (10): CD006015 [PubMed]
3. Adverse effects
  1. Suicidal Ideation
  2. Gynecomastia
  3. Sexual Dysfunction (Erectile Dysfunction, decreased libido, abnormal ejaculation)
  4. High grade Prostate Cancer (Finasteride, due to delayed diagnosis with lower PSA values)
4. Agents
  1. Dutasteride (Avodart, Duagen) 0.5 mg orally daily
  2. Finasteride (Proscar) 5 mg orally daily
Protocol: Combination Option
1. Consider for large Prostate and moderate obstructive symptoms
2. First 2-3 months (allows for delay in 5a-Reductase Inhibitor activity onset)
  1. Alpha Adrenergic Antagonist and
  2. 5a-Reductase Inhibitor
3. Next
  1. Continue 5a-Reductase Inhibitor
  2. Taper or discontinue Alpha Adrenergic Antagonist
Anticholinergic Agents
1. May be used as an adjunct in combination with other agents above (esp. alpha adrenergic blockers)
2. May reduce Bladder contractions and improve irritative urinary symptoms (urgency, frequency)
3. Increased risk of Urinary Retention, although risk of acute urinary obstruction <1%
4. Risk of confusion in elderly patients (see Beers List)
5. Preparations
  1. Oxybutynin ER (Ditropan XL) 10 mg orally daily (generic)
  2. Fesoterodine (Toviaz) 4-8 mg orally daily
  3. Solifenacin (Vesicare) 5 mg orally daily
  4. Tolterodine ER (Detrol LA) 4 mg orally daily

Management
Alternative Medications (low efficacy)

Saw Palmetto 160 mg orally twice daily
1. Mixed results from studies regarding efficacy (see Saw Palmetto)
2. Initial studies suggested benefit, but 2006 Placebo-controlled study did not
  1. Bent (2006) N Engl J Med 354: 557-66 [PubMed]
3. Did not reduce Nocturia, Peak Urine Flow, Prostate size or AUA Symptom Index for BPH
  1. Tacklind (2012) Cochrane Database Syst Rev (12): CD001423 [PubMed]
4. Cochrane Review 2023 also found no benefit for urologic symptoms in BPH
  1. Franco (2023) Cochrane Database Syst Rev 6(6):CD001423 +PMID: 37345871 [PubMed]
Soy products (Isoflavone Genistein)
1. Tofu contains high concentrations of Genistein
2. Trinovin (OTC Genistein derived from red clover)
  1. Reduced BPH symptoms at 40-80 mg daily (small trial)
3. References
  1. Lowe (2000) Patient Care 34:191-203 [PubMed]

Management
Acute Urinary Obstruction

Evaluation
1. Consider recent medications predisposing to urinary obstruction (especially Anticholinergics such as Antihistamines)
  1. See Medication Causes of Urinary Retention
2. Consider alternative causes of urinary obstruction (e.g. pelvic mass, neurologic disorders such as cauda equina)
  1. See Urinary Retention
3. Urinalysis
4. Prostate exam
  1. Assess size
  2. Exquisite tenderness suggests Acute Prostatitis
Urinary Catheterization
1. See Urethral Catheterization
2. Indicated for complete obstruction with significant post-void residual
3. Pre-anesthetize Urethra (e.g. Lidocaine jelly)
4. Use a Coude Catheter
5. Larger catheters (e.g. 20F) may pass more easily than smaller catheters
6. Plan follow-up with urology in following 7-10 days (earlier catheter removal may fail)
Medications that decrease urinary obstruction acutely
1. Start agent with or without catheterization
2. Alpha Adrenergic Antagonists (see above)
  1. Tamsulosin (Flomax) 0.4 mg orally daily
  2. Alfuzosin XL (Uroxatral) 10 mg daily for 2 days
Antibiotic Indications
1. Treat Acute Prostatitis or Urinary Tract Infection if present
References
1. Henry (2013) Urology Rapid Assessment, EM Boot Camp, CEME

Management
Surgery Invasive

Indications
1. Benign Prostatic Hyperplasia Symptom Index 20 or higher
2. Failed medical therapy
3. Refractory Urinary Retention
4. Recurrent Urinary Tract Infections
5. Persistant Hematuria (gross or microscopic)
6. Bladder stones
7. Renal Insufficiency
8. Bladder decompensation (decreased detrusor Muscle Contractions)
Invasive Procedures
1. Transurethral Resection of the Prostate (TURP)
  1. Most established BPH surgery with excellent longterm outcome data
  2. Inpatient procedure with longer hospital stays
  3. Complications include Erectile Dysfunction, Bladder neck contracture, irritative voiding
  4. Risk of Hyponatremia and TURP Syndrome
    1. Modified procedure with Bipolar TURP reduces these complications
2. Open Prostatectomy
  1. Most invasive procedure for BPH
  2. Risk of Hemorrhage and other Prostatectomy-related complications
  3. Indications (rarely used for BPH alone)
    1. Very large Prostate size (>80 ml)
    2. Large median Prostate lobe protruding into Bladder
    3. Urethral Diverticulum

Management
Surgery with Minimally Invasive Procedures

Advantages
1. Lower complication rates
2. Most of these procedures are performed outpatient
Disadvantages
1. Typically no tissue samples for histopathology testing
2. Some procedures are less effective or have higher failure rates than TURP
Procedures inpatient (with good efficacy compared with TURP)
1. Transurethral Incision of the Prostate (TUIP)
  1. Indicated for BPH in smaller Prostate size (<30 ml)
2. Transurethral Laser Induced Prostatectomy (TULIP)
  1. Ultrasound-guided Nd-Yag laser (or Holmium: Yag Laser)
  2. Shorter procedure and fewer complications than TURP
  3. Similar efficacy for large Prostates (>60 grams) as TURP at 2 years
  4. Wilson (2006) Eur Urol 50(3):569-73 [PubMed]
  5. Zhang (2019) Prostate Cancer Prostatic Dis 22(4): 493-508 [PubMed]
Procedures outpatient
1. Transurethral Microwave Thermotherapy (TUMT)
  1. Microwave probe heats to over 45 C)
  2. Safe, effective method for Urinary Retention relief
  3. Franco (2021) Cochrane Database Syst Rev (6): CD004135 [PubMed]
2. Transurethral Vaporization of the Prostate (TUVP)
3. Transurethral Electrovaporization Prostate (TVP)
4. Water Vapour Thermal Therapy (WVTT, Rezum)
  1. Westwood (2018) Ther Adv Urol 10(11):327-33 +PMID: 30344644 [PubMed]
5. Hot Water Ballon Thermoablation
  1. Experimental procedure with good outcomes
  2. Minimal discomfort
6. Prostatic Urethral Lift
  1. Sonksen (2015) Eur Urol 68(4): 643-52 [PubMed]
7. Robotic Water Jet Ablation
  1. Gilling (2018) J Urol 199(5): 1252-61 [PubMed]
Procedures falling out of favor due to low efficacy or higher risk
1. Transurethral Needle Ablation of Prostate (TUNA)
  1. High failure rate (23% at 5 years, 83% at 10 years)
  2. Rosario (2007) J Urol 177(3): 1047-51 [PubMed]
2. Urethral stent
  1. Risk of infection and re-blockage
  2. Indications
    1. BPH patients with high surgical risk
    2. Short Life Expectancy
3. Transurethral Balloon Dilation
  1. Rarely used due to high rate of symptom recurrence

Complications

BPH is not related to Prostate Cancer development
1. However BPH is a risk factor for Prostate Cancer (RR 4) and Bladder Cancer (RR 3)
2. Dai (2016) Medicine 95(18): e3493 [PubMed]
Obstructive complications
1. Postrenal Azotemia
2. Hydronephrosis
3. Bladder decompensation
  1. Overflow Incontinence
  2. Bladder hypertrophy
4. Urosepsis

References

(2022) Presc Lett 29(1): 2-3
Cooner (1994) Prostate Disease, AAFP, p. 9-15
Dornbland (1992) Adult Ambulatory Care, p. 249-52
Macchia (Feb, 1997) Consultant, p.336-45
Arnold (2023) Am Fam Physician 107(6): 613-22 [PubMed]
Corica (2000) Urology 56:76-81 [PubMed]
Donovan (2000) J Urol 164:65-70 [PubMed]
Dull (2002) Am Fam Physician 66(1):77-84 [PubMed]
Edwards (2008) Am Fam Physician 77(10): 1403-10 [PubMed]
Guthrie (1997) Postgrad Med 101(5):141-62 [PubMed]
Lerner (2021) J Urol 206(4): 806-17 [PubMed]
Oesterling (1995) N Engl J Med 332(2):99-109 [PubMed]
Pearson (2014) Am Fam Physician 90(11): 769-74 [PubMed]
Yuan (2015) Medicine 94(27): e974 [PubMed]