Pathophysiology of Benign Prostate Hyperplasia

What is benign prostate hyperplasia?

• increase number of prostate cells (non-cancer)

• common cause of urinary dysfunction symptoms in elderly men

• most common benign neoplasm (abnormal growth) in men

BPH prevalence

• peak incidence is mid-60s

  • rare before 50

• 80-90% by age 80

  • “all” males will develop BPH if live long enough

BPH risk factors

• high levels of T, DHT, estradiol, insulin-like growth factor and inflammatory markers (CRP)

• obesity

• diabetes

• high alcohol

• physical inactivity

*mechanisms poorly understood

What is the normal growth of the prostate over male lifetime?

• Prior to puberty

  • size of pea, ~1g

• puberty to 25-30 years

  • grows to peach-pit, ~15-20g

• > 40y

  • second growth spurt, can 4x in size

Location of prostate

Encircles part of urethra inferior to bladder

Prostate purpose

• secretes milky, slightly acid fluid, playing role in sperm activation

  • citrate (nutrients)

  • proteolytic enzymes & prostate specific antigen (coagulate semen)

  • seminal plasmin (antibiotic protein)

  • relaxin (increase sperm motility)

• contributes 1/3 of total semen volume

The 3 types of prostate tissues and their roles

• epithelial tissue

  • produces secretions

• stromal tissue

  • smooth muscle

  • contain many alpha-1 adrenergic receptors (mostly a1-A)

  • normal prostate 2:1 stromal-epithelial; BPH 5:1

• capsule

  • fibrous connective tissue and smooth muscle

  • contains alpha-1 adrenergic receptor

BPH pathogenesis

• exact cause unclear and not completely understood

• thought that DHT and type II 5alpha-reductase to play a central role

• only occurs if normal functioning testes

• proliferation of stromal and epithelial cells; and dynamic and static components

What is the static component of prostate enlargement?

• increase smooth muscle and epithelial cell proliferation

  • mostly by DHT

• causes anatomic enlargement of prostate

  • physically blocks bladder neck and obstructs urinary flow

What is the dynamic component to prostate enlargement?

• increase smooth muscle tone in prostate and bladder neck

  • via alpha-adrenergic receptors

What is the correlation of BPH and prostate cancer?

• BPH and prostate cancer may occur concurrently

• BPH does not predispose patients to developing prostate cancer

  • may catch it more, because more regularly monitored

• BPH occurs in central/transitional zone and prostate cancer originate in peripheral zone

  • cancer recognized with rectal exam

BPH pathogenesis progression

BPH → BPE (benign prostatic enlargement) → BPO (benign prostatic obstruction)

What can occur if you get to BPO?

Large risk of damage to bladder, nerve cells, sepsis.

BPH clinical presentation

• weak urine stream

• frequent urination

• dribbling after urination

• urge to urinate

• leakage or urine (overflow incontinence)

• frequent urination during night

What is LUTS?

• Lower urinary tract symptoms

• obstructive + irritative symptoms

• non-specific and may be caused by other diseases

What are the obstructive voiding symptoms?

• slow urinary flow

• intermittent urinary stream

• straining to void/difficulty initiating

• occasional mid-steam stoppage

• post-void dribbling

What are the irritative storage symptoms?

• increase daytime frequency

• increase nocturia

• increase urgency

• urinary retention

• UTIs

• urinary incontinence (uncommon in BPH)

What are the mandatory investigations?

• history

  • previous surgeries, trauma (that impacts bladder or prostate)

  • current medications that may affect

• Urinalysis

  • rule out infection or blood

• Digital rectal exam (DRE)

  • normal prostate firm and nontender

What medications may affect BPH symptoms?

• Anticholinergics - bladder contractility

• sympathomimetics - urinary outflow

What are the recommended investigations?

• symptoms survey

  • AUA score

  • IPSS

  • Boyarsky

• Prostate specific antigen (PSA) level

  • measure prior to treatment with 5alpha-reductase inhibitor

What are the optional investigations?

• SrCr

  • if high, might be due to bladder obstruction (AKI) or renal disease

• Urine cytology

  • screen bladder cancer

• Uroflow

  • if <15mL/sec = some obstructive disease

• Voiding diary

• Post-void residual (PVR)

  • normal <50mL (up to 100mL in older men)

  • very concerning if > 200mL = bladder obstruction or weakness

• sexual function questionnaire