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Benign prostatic hyperplasia

Definition
  • Lower urinary tract symptoms consequent upon bladder outlet obstruction due to BPH are predominantly due to 2 components
    • A static component related to an increase in benign prostatic tissue narrowing the urethral lumen
    • A dynamic component related to an increase in prostatic smooth muscle tone mediated by alpha-adrenergic receptors
  • Symptoms related to bladder outlet obstruction may also be contributed by bladder over-activity. [1]
Risk Factors
  • Age over 50 years
    • Histological and lower urinary tract voiding symptoms increase with age. [2]
  • Family history
    • Men with an affected family relative, diagnosed with BPH before age 60 years, are at an increased risk.
    • In addition, twin studies indicate a 3.3-fold higher risk in monozygotic twins with affected siblings. [6]
  • Non-Asian race
    • A US study showed that Asian men have smaller prostates at any given age with less need for invasive surgery compared with white or black men. [7] 
  • Cigarette smoking
    • A potential causal relation has been associated with lower urinary tract symptoms. [8] [9] 
  • Male pattern baldness
    • A potential causal relation has been associated with lower urinary tract voiding symptoms. [8] [9] 
  • Metabolic syndrome
    • A potential causal relation has been associated with lower urinary tract voiding symptoms. [10]
Differential diagnosis
  • Overactive bladder
    • Frequent urge to urinate with possible incontinence and nocturia.
  • Prostatitis
    • Fever, suprapubic or low back pain, tender, enlarged prostate gland on rectal examination is more consistent with prostatitis.
  • Prostate cancer
    • Abnormal digital rectal examination with prostate nodules or asymmetry is more consistent with prostate cancer
  • UTI
    • Presence of fever, dysuria, suprapubic or low back pain is more consistent with UTI.
  • Bladder cancer
    • Haematuria, suprapubic pain, bladder spasms with abnormal voiding, history of tobacco abuse, unknown major risk factor is more consistent with bladder cancer.
  • Neurogenic bladder
    • Storage abnormality in patients with involuntary bladder contractions.
    • Usually seen in patients with vascular disease, Parkinson disease, multiple sclerosis or diabetes mellitus with neuropathy. [15]
  • Urethral stricture
    • History of straddle injury or prior urological surgery with obstructive symptoms is more consistent with urethral stricture.
Epidemiology
  • Global differences in epidemiology statistics are somewhat dependent upon how BPH is defined.
  • However, the prevalence of histological BPH does increase with age
    • Afects approximately 42% of men between the ages of 51 and 60 years, and 82% of men between the ages of 71 and 80 years. [2] 
  • In 2000, BPH generated $1.1 billion in healthcare costs and accounted for over 4.4 million office visits, 117,000 emergency department visits and 105,000 hospitalizations in the US. [3]
Aetiology
  • Hyperplasia of the epithelial and stromal compartments, particularly in the transitional zone, may be attributed to various factors
    • Including shifts in age-related hormonal changes creating androgen/oestrogen imbalances
  • Changes in prostatic stromal-epithelial interactions that occur with ageing and increases in prostatic stem cell numbers are also aetiological considerations
  • Progression from pathological BPH to clinical BPH (i.e., the presence of symptoms) may require additional factors
    • Such as prostatitis, vascular affects, and changes in the glandular capsule. [4]
Clinical features
  • Storage symptoms
    • Frequency, urgency, and nocturia
  • Voiding symptoms
    • Weak stream, hesitancy, intermittency, straining, incomplete emptying, and post-void dribbling
  • Fever with dysuria
    • Suggestive of complicated UTI
  • Urinary retention
    • Acute complication
Pathophysiology
  • BPH involves hyperplasia of both epithelial and stromal prostatic components.
  • A key characteristic of BPH is increased stromal:epithelial ratio.
  • Over time, prostatic hyperplasia can result in bladder outlet obstruction.
  • Obstruction has both:
    • a prostatic component due to increased epithelial tissue, particularly in a transition zone
    • a dynamic component due to increases in stromal smooth muscle tone
  • A large number of alpha-adrenergic receptors are present in the prostate capsule, stroma, and the bladder neck.
    • The predominant alpha-1 receptor in prostatic stromal tissue is the alpha-1A receptor.
  • Treatment of symptomatic BPH is mainly accomplished via:
    • reduction of the size of the glandular component
      • following inhibition of the formation of dihydrotestosterone (DHT) by 5-alpha-reductase inhibitors
    • relaxation of smooth muscle tone
      • with alpha-blockers
  • Select surgical intervention (e.g., transurethral resection) alleviates symptoms of urinary obstruction by reduction of prostatic bulk
Investigations
  • urinalysis
    • pyuria (pus in urine)
  • PSA
    • elevation greater than age guideline
  • International Prostate Symptom Score (IPSS)
    • score of 0 to 35 to define severity of symptoms
  • global bother score
    • score 0 to 6 dependent on degree of bother
  • volume charting
    • diary of frequency of voiding
  • ultrasound
    • hydronephrosis, mass, urolithiasis
  • CT abdomen/pelvis
    • mass, hydronephrosis, urolithiasis
  • cystoscopy
    • mass, stone, stricture
  • uroflowmetry
    • less than 20 mL/second
  • urodynamic study
    • abnormal bladder pressure, abnormal bladder voiding
Management

a) conservative
  • watchful waiting
  • behavioural management programme
    • Limitation of fluids
    • bladder training focused on timed and complete voiding
    • treatment of constipation
b) medical
  • Alpha-blockers work through smooth muscle relaxation in the prostate and bladder neck.
    • The predominant receptor type in the prostate and bladder is the alpha-1A receptor
    • Alpha-blockers specific for this receptor are more prostate selective and have less vascular effects
    • Long-acting alpha-1 antagonists include terazosin and doxazosin
    • Alfuzosin is a modified release alpha-1A antagonist
    • Tamsulosin and silodosin are a long-acting sub-type (alpha-1A) selective alpha-blocker
  • 5-alpha-reductase inhibitors work through reduction of serum dihydrotestosterone (DHT)
    • Inhibit DHT formation, reducing prostate volume by 20% to 25%
    • They have been shown to reduce the risk for acute urinary retention and the need for invasive therapy by approximately 50%
    • Finasteride is a type II 5-alpha-reductase inhibitor that reduces serum DHT by 75%
    • Dutasteride is a type I and II 5-alpha-reductase inhibitor with 90% to 95% reduction of serum DHT
c) surgical
  • Minimally invasive therapy
    • photoselective vaporisation
    • transurethral needle ablation
    • transurethral microwave therapy
    • visual laser ablation
    • interstitial laser coagulation
  • Transurethral resection of the prostate (TURP) or transurethral vaporisation (TUVP)
  • Open prostatectomy or holmium laser enucleation (HoLEP)
Prognosis
  • The majority of patients with BPH can expect at least moderate improvement of their symptoms with a decreased bother score and improved quality of life
  • Lower urinary tract symptoms (LUTS), secondary to BPH, may affect sexual wellbeing including erectile function
  • Medical therapy for BPH may also effect sexual function, beneficially and harmfully, so this must be considered on an individual basis
  • Some studies suggest that patients with a low risk for progression may be able to discontinue first-line therapy with alpha-blockers after several months of therapy
    • However, the majority of patients will require ongoing therapy.
  • Clinical progression of BPH (as defined by symptom progression >3 points) occurs in approximately 20% of patients
    • Approximately 2.5% of patients will develop acute urinary retention and another 6% will require invasive therapy over a 5-year time-frame
    • Risk for BPH progression is increased in patients with higher prostate volumes and PSA levels
    • Risk reduction of clinical BPH progression has been demonstrated by 39% in patients on doxazosin and 34% in patients on finasteride
      • Patients on combination therapy had a 66% reduction in clinical BPH progression
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