creation date: 2025-05-01 18:04
tags: Pathologies
Benign Prostatic Hyperplasia
Background
Definitions
Benign prostatic hyperplasia (BPH) is a common condition in older males. Histologically, there is an increased number of stromal and glandular epithelial cells in the transition zone of the prostate that can result in prostatic enlargement and bladder outlet obstruction.
Etiology and Pathogenesis
The pathophysiology of the occurrence of lower urinary tract symptoms (LUTS) as a result of BPH is likely multifactorial.
While an enlarged prostate can cause benign prostatic obstruction as well as increased smooth muscle tone and resistance, secondary effects such as detrusor instability and overactive bladder can occur from the obstruction and further contribute to LUTS. Age-related changes to detrusor contraction and compliance also compounds effects.
There are several processes that are suggested to be involved:
- Cell immortalization due to an imbalance between prostatic cellular proliferation and apoptosis. Proliferation requires dihydrotestosterone (DHT) which is converted from testosterone by 5-alpha-reductase.
- Systemic and local inflammation due to obesity, autoimmune processes, and chronic infection. Serum level C-reactive protein levels correlate with LUTS severity.
- Prostatic fibrosis promoted by chemokines may result in periurethral rigidity and fibrosis.
Conditions may further exacerbate LUTS:
- Cardiovascular disease risk often overlaps with LUTS such as alpha-adrenergic receptors and autonomic hyperactivity likely has a role. Excessive BNP production in patients with heart failure may also worsen urine production.
- Neurological conditions may influence detrusor function and stability (eg. detrusor overactivity with Parkinson disease)
- Diabetes mellitus may result in decreased bladder sensation, decreased detrusor contractility, and incomplete bladder emptying. Increased glucose filtration can result in osmotic diuresis and increase urine production.
Clinical Presentation
Signs & Symptoms
While BPH can be asymptomatic, it often leads to lower urinary tract symptoms (LUTS). Typical manifestation of LUTS include:
- Storage symptoms: frequency, urgency, nocturia, incontinence
- Voiding symptoms: slow stream, straining to void, urinary intermittency or hesitancy, splitting of stream, terminal dribbling
Physical findings include a nontender, enlarged prostate on DRE.
History & Physical Exam
History may find the progression of symptoms over a period of years. Complaints regarding symptoms of hematuria, incontinence, or urinary retention should prompt urology referral.
Features regarding history of trauma, smoking history (for bladder cancer), use of drugs that can impair bladder function (eg. anticholinergics or sympathominetics), and neurogenic diseases should be elicited.
A voiding diary of 3 days can also be obtained from the patient in cases of nocturia.
An assessment of symptom severity can be made using the American Urological Association urinary symptom score/International Prostate Symptom Score (AUA-SI/IPSS).
- Score 0-7: mild symptoms
- Score 8-25: moderate to severe symptoms
Physical exam should include neurologic screen, abdominal exam, and GU exam including a DRE.
Risk factors
Unmodifiable:
- Race - may be more severe in Black men than White, both of which more than Asian
- Genetic susceptibility - important determinants of LUTS
- Family history of bladder cancer, but not prostate cancer
Modifiable: - Obesity and metabolic syndrome (related to increased autonomic tone)
- Coffee/caffeine intake
- Physical activity - lower levels of physical activity and frailty associated with greater risk
- Alcohol consumption - excessive (≥3 per day) may lower risk due to androgen depression
- Dietary factor - may be associated with micronutrients involved in the prevention of oxidative damage or cell growth/differentiation
Diagnosis
Criteria
Diagnosis is made using the presence of storage, voiding, and/or irrative urinary symptoms in absence of evidence of other causes of LUTS.
Diagnosis does not require histologic confirmation unless there are suspicion for prostate cancer.
Work-up
Beyond a detailed history and physical, laboratory tests can aid in ruling alternative etiologies of LUTS. Routinely, a urinalysis is obtained.
In some circumstances further studies may be done:
- Urine culture - if suggestion of UTI
- Serum creatinine - if suggestion of kidney function impairment or bladder outlet obstruction
If there is suspicion of an enlarged prostate, a PSA level can be tested as a proxy for prostate size.
- PSA ≥1.5 ng/mL is typically considered a marker of enlargement
- A prostate volume ≥30 g on transrectal US, MRI, or CT pelvis.
A measurement of post-void residual volume is also done to evaluate for retention.
- Bladder ultrasound to estimate
- Use of a straight catheter following spontaneous void
Moderate-to-severe LUTS is associated with increased incidence of urinary retention. Normal men have <12 mL of PVR volume.
Other additional imaging and testing may be done for select patients and is typically guided by urology.
- Prostate imaging - not recommended and only if prostate volume important
- Cystoscopy - not used with assessment but may be considered if history suggests urethral stricture or bladder neck contracture
- Urodynamic testing - determine flow rates, done by urology
Differential
There are a number of causes for LUTS ranging from obstructive urologic causes to nonurologic conditions such as neurologic diseases and may be considered as part of a LUTS workup.
Other considerations include:
- UTI - dysuria
- Prostatitis - if tender prostate
- Prostatic abscess - CT
- Malignancy - if presence of asymmetry or nodules
Red Flags / Complications
Untreated BPH may result in acute urinary retention.
Chronic obstruction and incomplete emptying increases risk of:
- UTI
- Bladder stones
- Bladder diverticuli
- Kidney damage
Referral for urology may/should be considered if:
- Severe symptoms or pain
- <45 years old
- Abnormal DRE
- Hematuria
- Elevated PSA
- Dysuria with suspicion of bladder cancer
- Incontinence
- Neurologic disease known to impact LUTS
- Urinary retention >250 mL
- Suspicion of other urologic disease
Management
Lifestyle / Social
Modifications to lifestyle and behaviours may lessen the symptoms of LUTS and should be implemented with pharmacologic therapy.
Lifestyle:
- Limiting fluid intake prior to bedtime or travel
- Limiting intake of mild diuretics (eg. caffeine, alcohol)
- Limiting intake of bladder irritants (eg. highly seasoned foods)
- Avoiding constipation
- Increasing activity
- Weight control
Behavioural:
- Timed voiding regimens - for patients with high PVR (eg. urinate every 90-120 minutes)
- Double-voiding - for patients with obstructive symptoms (eg. urinate 1-2 mins after initial void)
- Pelvic floor training - kegals may aid with urgency symptoms
Pharmacological / Interventional
Approach to pharmacologic therapy is based on the severity of symptoms as determined by AUA-SI/IPSS discussed above.
Mild, minimally bothersome LUTS
Typically can be managed with lifestyle and behavioural modifications alone.
In the rare circumstances of significant enlargement (eg. incidentally finding) with mild/no LUTS, 5-alpha reductase inhibitors (5-ARIs) may be considered.
- Finasteride 5mg PO daily
- Dutasteride 0.5mg daily
Moderate-to-severe, bothersome LUTS with no evidence of enlarged prostate
With patients with persistent LUTS without an enlarged prostate, monotherapy with a selective alpha-1 adrenergic blocker such as the following is recommended:
- Tamsulosin (Flomax) 0.4mg PO once daily
- Silodosin 8mg PO once daily with meal
- Alvuzosin 10mg PO once daily
A nonselective alpha-1 antagonist may be considered if selective not available but may have more adverse effects. In either case, blood pressure should be monitored due to the risk of hypotension.
In addition, the following options can be added in combination in some circumstances:
- Beta-3 adrenergic agonist and antimuscarinics - if OAB symptoms predominate
- In patients with erectile dysfunction, PDE-5 inhibitors may reduce LUTS symptoms and can be used in conjunction with alpha-1 antagonists. This is not recommended for isolated LUTS due to greater risk of hypotension.
Note, alpha-1 antagonist do not stop progression of BPH and must be used indefinitely for symptom management.
Moderate-to-severe, bothersome LUTS with evidence of enlarged prostate
In cases where the prostate is enlarged, a combination of alpha-1 antagonist and 5-ARI is used.
Note that it can take several months for 5-ARI treatment to work while alpha-1 antagonists typically work within a few days.
Combination of 5-ARI and PDE-5i are not recommended as there is no evidence of additional benefit.
Surgical alternative
In patients where medications are contraindicated or prefer not to, a second-line surgical treatment is suggested. A number of options are available but typically involve a cystoscope and resection, ablation, or compression of prostatic tissue.
Most common is a transurethral incision of the prostate (TURP) but vaporization using electrodes or laser as well as other minimally invasive procedures are more frequently used now.