Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is a condition indicating an increase in the number of stromal and epithelial cells within the prostate gland (transition zone). Benign prostatic hyperplasia is common in men > 50 years of age and may greatly affect their quality of life. The development of BPH involves modifiable and non-modifiable risk factors, which lead to anatomic obstruction and downstream effects on other organ systems. Clinically, patients present with a combination of obstructive and bladder storage symptoms. Diagnosis is made by determining the severity of voiding symptoms through a variety of non-invasive (voiding diary, history, physical examination) and invasive (cystoscopy, urodynamics, transrectal ultrasound imaging) tools. Treatment is multimodal with medical and surgical components (prostatectomy) utilized in combination.

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Overview

Definition

Benign prostatic hyperplasia (BPH) is a histologic diagnosis with an increase in the total number of stromal and epithelial cells within the transition zone of the prostate gland.

The overall size of the prostate gland does not correlate with the degree of symptoms.

Benign prostatic hyperplasia occurs with bladder outlet obstruction (BOO), leading to lower urinary tract symptoms (LUTS), which can greatly affect quality of life.

Benign prostatic hyperplasia

Illustration comparing the normal prostate (left image) and an enlarged prostate or BPH (right image), which is associated with bladder outlet obstruction

Image: “BPH” by National Institutes of Health. License: Public Domain

Anatomy

  • Prostate gland: organ under the bladder that secretes fluid into the ejaculate (which together with the sperm and seminal vesicle fluid, make up the semen)
  • Prostate zonal anatomy:
    • Peripheral zone: 
      • Consists of over 70% of the prostate gland
      • Most prostate cancers are in the peripheral zone.
      • Closest to the rectum
    • Central zone: about 25% of the prostate gland with its ducts close to the ejaculatory duct orifices
    • Transition zone: 
      • About 5% of the prostate gland and surrounds the proximal urethra 
      • Key area of concern for BPH
Prostate gland and main prostate zones

Prostate gland and main prostate zones: peripheral, transitional, and central zones in relation to other structures of the male genitourinary system

Image: “Zones of the prostate” by Mikael Häggström, M.D.. License: CC0

Epidemiology

Prevalence of BPH increases with age:

  • 40%–50% of men aged > 50 years are affected.
  • Varying disease severity noted, with implications on quality of life (with both physical and psychologic effects)

Risk factors:

  • Modifiable: 
    • Metabolic syndrome: Alteration of testosterone to estrogen ratio may lead to larger prostate growth. 
    • Fluid intake: Coffee/tea and other caffeinated beverages increase risk of LUTS.
    • Diet: High antioxidant-containing foods (lycopene, beta carotene) may be associated with decreasing LUTS incidence. 
  • Non-modifiable: 
    • Race: Black men age < 65 are more likely to require BPH treatment versus their White counterparts. 
    • Genetics: Significant family history of BPH leads to earlier diagnosis and symptoms of LUTS.
    • Hormones: Serum testosterone or dihydrotestosterone (DHT) are not higher in men with BPH.

Pathophysiology

  • Androgens, testosterone, and DHT (the more potent androgen) play a key role in BPH:
    •  ↑ Prostate cell proliferation 
    • Inhibit cell death
  • BPH directly leads to:
    • Urethral compression: Enlarged prostate gland compresses nearby urethra, causing LUTS.
    • BOO: 
      • Incomplete voiding and/or increased storage of urine
      • Increased bladder smooth muscle tone and pressure lead to decreased compliance. 
  • BPH with BOO results in secondary detrusor instability or overactive bladder (also causing LUTS).

Clinical Presentation

LUTS

  • Voiding: difficulty with starting/stopping urination, weak stream, straining, or dribbling
  • Storage: sudden urgency, frequency, incontinence, and nocturia

International Prostate Symptom Score (IPSS) questionnaire

  • Purpose:
    • Helps screen and diagnose BPH 
    • Monitor treatment response.
  • Summary of questionnaire (questions on 7 urinary symptoms, with answers assigned points from no symptoms or 0 to almost always or 5):
    • Incomplete emptying
    • Frequency
    • Intermittency
    • Urgency
    • Weak stream
    • Straining
    • Nocturia
  • Interpretation:
    • Mild (symptom score ≤ 7)
    • Moderate (symptom score range 8–19)
    • Severe (symptom score range 20–35)

Diagnosis

Clinical findings

  • History: voiding patterns, fluid intake, diet, pertinent medical history, current medications  
  • Physical exam: 
    • Abdominal: Search for suprapubic tenderness, distended/palpable bladder, hernias, prior surgical scars.
    • Pelvis: motor/sensory function, inguinal hernias 
    • Genitourinary:
      • Basic genital exam
      • Digital rectal exam (DRE): assesses size of the prostate gland (normally about the size of a walnut), tenderness, nodules 
      • Post-void residual bladder scan to assess how well the patient empties
Digital rectal exam

Digital rectal exam (side view of the male reproductive and urinary anatomy, including the prostate, rectum, and bladder):
The doctor inserts a gloved, lubricated finger into the rectum and feels the prostate to check for abnormalities.

Image: “Digital rectal exam” by Unknown illustrator. License: Public Domain

Laboratory tests

  • Urinalysis: identifies hematuria, proteinuria, bacteriuria 
  • Serum creatinine: establishes baseline renal function 
  • Prostate-specific antigen (PSA) provides:
    • Additional information regarding prostate volume
    • Baseline value for future prostate cancer screening

Diagnostic procedures/imaging

  • Urodynamic testing: 
    • Attempts to reproduce patient’s symptoms in a simulated environment by filling the bladder with fluid
    • Assesses for detrusor overactivity, urinary incontinence, bladder compliance, urine flow curve
  • Transrectal ultrasound:
    • Not necessary for diagnosis of BPH, but helps with accurately estimating prostate volume 
    • Important for prostate biopsy under ultrasound guidance when assessing for possible prostate cancer
  • Cystoscopy:
    • Office procedure to view the prostate, bladder, urethra with a camera 
    • Assists in operative planning for BPH and to rule out other anatomic causes

Management

Non-surgical

  • Behavioral modifications:
    • Limiting fluid intake/bladder irritants (caffeine, alcohol)
    • Avoiding constipation 
    • Timed voiding regimens to improve bladder emptying 
  • Medical therapy: 
    • Alpha-adrenergic receptor blockers (tamsulosin, doxazosin):
      • Alpha-1 adrenergic receptors are located on prostatic smooth muscle.
      • Blocking signals leads to relaxing the smooth muscle of the bladder neck and prostatic urethra. 
      • Side effects: dizziness, low blood pressure, rhinitis, retrograde ejaculation 
    • 5-alpha-reductase inhibitors (finasteride, dutasteride): 
      • Block steroidal conversion of testosterone to DHT
      • Overall effect of shrinking the prostate gland over a period of 6+ months 
      • Side effects: gynecomastia, decreased libido, retrograde ejaculation
    • Phosphodiesterase (PDE) type 5 inhibitors (tadalafil): 
      • Blocks degradative effects of PDE-5 in the smooth muscle cells, increasing action of cyclic guanosine monophosphate (cGMP)
      • Leads to relaxation of smooth muscle vasculature 
      • Side effects: headache, flushing, nasal congestion, unsafe drop in blood pressure if taken with nitrates  
    • Beta-3 adrenergic agonists (mirabegron):
      • Stimulate detrusor beta-3 adrenergic receptors to promote bladder relaxation 
      • Effective for treating overactive bladder symptoms and promote bladder storage 
      • Side effects: increased blood pressure 
    • Anticholinergics (oxybutynin): 
      • Muscarinic receptor blockers to treat irritative overactive bladder symptoms 
      • Side effects: dry mouth, constipation, confusion, dry eyes, blurry vision, sedation, urinary retention 
      • Critical to obtain post-void residual bladder scan to ensure patient is not retaining a large amount of urine prior to use

Surgical therapy

  • Indications: 
    • Acute urinary retention
    • Recurrent bladder stone
    • Chronic renal insufficiency secondary to BOO
    • Recurrent hematuria
    • LUTS refractory to medical treatment
  • Transurethral resection of the prostate (TURP):
    • Minimally invasive technique under cystoscopic guidance resection with a loop wire electrode 
    • Goal is to remove adenomatous tissue in the transition zone of the prostate and relieve obstruction. 
  • Simple prostatectomy: 
    • Invasive open or robotic procedure 
    • Reserved for patients with prostate glands > 80 g to enucleate the gland

Differential Diagnosis

  • Prostate cancer: the most common non-cutaneous cancer in men. Prostate cancer is a malignant neoplasm that arises from the prostate gland. Patients present with an abnormal DRE or with a consistently elevated PSA that leads to a prostate biopsy. The biopsy cores will provide a pathologic diagnosis of prostate malignancy. 
  • Urethral stricture: Similar to BPH, patients with urethral stricture may have chronic obstructive voiding symptoms such as decreased urinary stream and incomplete bladder emptying. A retrograde urethrogram or a voiding cystourethrogram, both tests that utilize contrast to outline the urethral anatomy and identify a potential stricture, are used to differentiate from BPH. 
  • Bladder neck contracture (BNC): most commonly seen after a prostatectomy or urologic instrumentation where scar tissue can form at the junction of the bladder outlet and the prostate. The scar tissue can cause outlet occlusion and narrowing with gradual decreasing urinary stream, incomplete emptying, and straining to void. Usually a cystoscopy will identify a BNC with its classic scar tissue appearance.

References

  1. McNeal, J.E. (1981). The zonal anatomy of the prostate, Prostate, 2(1), 35-49. https://doi.org/10.1002/pros.2990020105
  2. McVary, K.T. (2019). Epidemiology and pathophysiology of benign prostatic hyperplasia. UpToDate. Retrieved January 19, 2021, from https://www.uptodate.com/contents/epidemiology-and-pathophysiology-of-benign-prostatic-hyperplasia
  3. McVary, K.T. (2019). Clinical manifestations and diagnostic evaluation of benign prostatic hyperplasia. UpToDate. Retrieved January 19, 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnostic-evaluation-of-benign-prostatic-hyperplasia
  4. McVary, K.T. (2020). Medical treatment of benign prostatic hyperplasia. UptoDate. Retrieved January 19, 2021, from https://www.uptodate.com/contents/medical-treatment-of-benign-prostatic-hyperplasia
  5. Chughtai, B. (2020). Surgical BPH. AUA University: AUA Core Curriculum. https://university.auanet.org/modules/webapps/core/index.cfm#/corecontent/73

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