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bph

benign prostatic hyperplasia (BPH)

introduction

  • BPH is an extremely common disorder of men over aged 50 years
  • histologic evidence is present in 20% of men at age 40 years, increasing to 70% by age 60 and 90% by age 80
  • only 50% of those with histologic changes develop clinically detectable enlargement of the prostate, and of these, only 50% develop clinical symptoms ("Lower Urinary Tract Symptoms" or LUTS, formerly called prostatism).
  • 30% of Caucasian males over the age of 50 years have moderate to severe symptoms
  • nodular hyperplasia is NOT considered to be a premalignant lesion.

pathophysiology

  • the prostate normally functions to close off the bladder neck during orgasm to prevent retrograde ejaculation into the bladder.
  • circulating testosterone is converted by type 2 5-alpha reductase in prostate stromal cells to dihydrotestosterone (DHT) which is a more potent and longer binding agent activating nuclear androgen receptors on both stromal and epithelial cells resulting in synthesis of growth factors and thus the resultant hyperplasia.
  • castrated males (ie, who are unable to make testosterone) do not develop BPH
  • there may be a role for hyperinsulinaemia to contribute to prostatic growth
  • BPH originates in the transition zone surrounding the urethra
  • in patients with BPH, the prostate usually weighs 60-100g
  • the combination of increased size of the prostate tissue, with smooth muscle mediated contraction of the prostate results in urethral obstruction.
  • patients experience increased urinary frequency, nocturia, difficulty in starting and stopping the stream of urine, overflow dribbling, and dysuria.
  • the symptoms are not only due to the bladder outlet obstruction itself, but are also due to the secondary hypertophic effects on the bladder wall which becomes thickened, trabeculated and irritable with increased sensitivity (detrusor over-activity) to even small bladder volumes resulting in urinary frequency.
  • increased resistance to flow results in bladder hypertrophy and distension with risk of sudden onset of acute urinary retention.
  • inability to empty the bladder creates a reservoir of residual urine which is a common source of infection and urinary tract infections (UTIs) / cystitis, and may result in bladder stones (3.4% of autopsies with BPH vs 0.4% in those without BPH).

prevalence

  • rises to over 20% by age 50yrs, then to 40% by age 60yrs, then 70% by age 70yrs, 80% by 80yrs, 90% by 90yrs

natural history and progression

  • there does not appear to be a causal relationship with prostate cancer which generally starts in the peripheral part of the prostate while BPH is a problem of the central or transitional part of the prostate
  • a 60yr old with mod-severe symptoms of BPH has a ~14% chance of developing retention (AUR) over next 10 yrs
    • risk factors for AUR:
      • age
      • severity of obstructive symptoms
      • prostatic volume
        • NB. transabdominal US over-estimates prostatic volume by around 50%. Transrectal US is now rarely used
      • PSA > 2.5
      • if PH AUR and no Rx, 50% will have recurrence AUR within 1 wk, and 2/3rds in 1 year
      • post-void residual bladder volumes > 100ml (although this is no longer an indication for surgery as watchful waiting has shown this is not a predictor of need for surgery, but it probably does increase risk of UTI or AUR)
      • acute precipitant
  • 80% of men with BPH do not have progressively worse symptoms
    • a third of men with BPH appear to have REDUCED symptoms over 5yrs even without Rx
  • 20% progress to worsening obstructive symptoms:
    • risk factors for progression:
      • older age
      • PH erectile dysfunction
      • lower HDL cholesterol
      • lower testosterone
      • lower income
      • mobility issues
      • poor mental health
      • BMI > 25
      • hypertension
      • back pain
      • excessive ethanol abuse
    • symptoms can be reduced by:
      • increased physical activity
      • alpha adrenergic blockers such as tamsulosin
      • 5-alpha-reductase inhibitor (although this takes over 12 months)
      • NB. Duodart has been shown to be more effective than alpha blocker alone

diagnostic workup

  • Serum PSA measurement (as a proxy for prostate size) and ultrasound predict both the natural history and progression of LUTS and BPH and the therapeutic response to 5 alpha-reductase inhibitors.
  • PR exam (DRE)
  • U&E
  • PSA (if > 10 year life expectancy)
    • PSA levels suggestive of prostate volume > 30mL and thus risk of progressive symptoms:
      • >1.3 ng ⁄ mL for men aged 50–59
      • >1.5 ng ⁄ mL for men aged 60–69
      • >1.7 ng ⁄ mL for men aged 70–79
  • MSU m/c/s
  • renal USS (not usually needed unless contemplating surgical Mx):
    • post-void residual volume
    • prostatic volume
      • prostate volume > 30mL are 3.5x more likely to suffer moderate-to-severe symptoms, 2.5x more likely to have decreased flow rates, and 3-4x more likely to have AUR compared with men with a prostate volume of < 30 mL
    • hydronephrosis
    • the size and shape of the prostate are of importance in selecting patients for transurethral microwave heat treatment, TUNA and other minimally invasive therapies, as well as for the selection of TUIP versus TURP. Furthermore, anatomical features, such as intravesical lobes, may impact the choice of therapy. Prostate size, as measured by ultrasound, is predictive of the natural history of BPH and the response to therapy with 5 alpha-reductase inhibitors.
  • LUTS severity score:
    • International Prostate Symptom Score [IPSS]:
      • original 7 question scoring:
        • 0-7 = mild symptoms
        • 8-19 = moderate
        • 20-35 = severe symptoms
  • maximum flow-rate (a proxy for urodynamic studies) and invasive urodynamic studies have limited ability to predict both natural history and therapeutic response, but they have been shown to predict the response to surgery and, less so, minimally invasive therapies. 1)
  • urethrocystoscopy may be appropriate in men with a history of microscopic or gross hematuria, urethral stricture (or risk factors, such as history of urethritis or urethral injury), bladder cancer, or prior lower urinary tract surgery (especially transurethral resection of the prostate transurethral prostatic resection (TURP)).

medical management

  • if daily urine output > 3L then reduce fluid intake
  • reduce fluid intake at bedtime if nocturnal polyuria a problem
  • moderate alcohol and caffeine intake
  • timed voiding schedules
  • watchful waiting is the preferred management strategy for patients with mild symptoms.
  • medical therapies are not as efficacious as surgical therapies but may provide adequate symptom relief with fewer and less serious associated adverse events
  • the landmark CombAT trial of the dutasteride-tamsulosin combination (Duodart) demonstrated that the combination significantly reduces both symptoms and the incidence of AUR and the number of men who required prostate surgery at 4 years by 66% vs tamsulosin monotherapy
    • as of June 2016, GP's can prescribe Duodart on PBS for mod-severe symptomatic BPH
    • it would be expected that dutasteride decreases PSA levels by 50% after 6 months
    • HOWEVER, 5 alpha reductase type II inhibitors may cause sexual dysfunction including penile desensitisation, erectile dysfunction, reduced ejaculatory volume, reduced libido and sexual arousal, and some of these appear to be persistent in some men after stopping Rx! 2)

alpha-adrenergic blockers

  • decrease prostate smooth muscle tone via inhibition of alpha-adrenergic receptors
  • eg. tamsulosin
  • efficacy is dose dependent for the titratable alpha blockers doxazosin and terazosin —the higher the dose, the greater the observed improvement.
  • maximum tolerable and effective doses have not been defined for any alpha blocker, but reported clinical data support the efficacy and safety of titrating patients to 8 mg of doxazosin, to 0.8 mg of tamsulosin (from 0.4 mg), and to 10 mg of terazosin.
  • primary adverse events reported with alpha-blocker therapy are orthostatic hypotension, dizziness, tiredness (asthenia), ejaculatory problems, and nasal congestion.

5-alpha-reductase inhibitors

  • block the synthesis of dihydrotestosterone from testosterone
  • eg. finasteride
  • are not appropriate treatments for men with LUTS who do not have evidence of prostatic enlargement.
  • less effective than an alpha blocker in improving LUTS
  • reduces the risk of subsequent acute urinary retention and the need for BPH-related surgery by ~67%
  • can reduce the size of the prostate, can increase peak urinary flow rate, and can reduce BPH symptoms.
  • lowers serum and intraprostatic dihydrotestosterone, but not to castration levels, and lowers serum PSA, but does not mask the PSA-based detection of prostate cancer.
  • adverse events are primarily sexually related and include decreased libido, ejaculatory dysfunction, and erectile dysfunction and are reversible and uncommon after the first year of therapy.
  • the combination of an alpha-adrenergic receptor blocker and a 5 alpha-reductase inhibitor (combination therapy) is an appropriate and effective treatment for patients with LUTS associated with demonstrable prostatic enlargement, but generally requires much more than 1 year Rx to demonstrate benefit over an alpha blocker alone.

surgical management

trans-urethral resection of the prostate (TURP)

  • has been the gold standard of Rx but has significant morbidity
    • 1% risk of urinary incontinence
    • retrograde ejaculation
    • an overall decline in sexual function that was identical to the watchful waiting treatment group.
    • dilutional hyponatremia that occurs when irrigant solution is absorbed into the bloodstream.
    • other complications that have been reported in more than 5% of patients include, in order of frequency: 65% sexual ejaculatory dysfunction (which may not be attributable to the surgery in all cases), 15% irritative voiding symptoms, 10% erectile dysfunction, bladder neck contracture, 8% the need for blood transfusion, 6% UTI, and hematuria, 5% require a secondary procedure.

alternative treatments to TURP

minimally invasive therapies

  • only effective in patients with prostates in a certain size range
  • common risks include irritative urinary symptoms that can persist for weeks and temporary urinary retention.
  • transurethral microwave heat treatments:
    • CoreTherm
    • Prostatron
    • Targis
    • TherMatrx
  • transurethral needle ablation (TUNA) using radiofrequency
  • UroLume stent
    • prostatic stents are associated with significant complications, such as encrustation, infection and chronic pain, their placement should be considered only in high-risk patients, especially those with urinary retention.

surgical therapies

  • high-intensity focused ultrasound
  • transurethral laser resection, vaporization or coagulation therapies
  • transurethral electrovaporisation
  • open prostatectomy
bph.txt · Last modified: 2018/04/17 14:46 (external edit)