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
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)
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:
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)
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)