Benign Prostatic Hyperplasia

(BPH)

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 Introduction
• The prostate

– a heart-shaped, chestnut-sized organ

– Encircles the portion of the proximal urethra

– located at the base of the urinary bladder

– Weighs 15-20g
• Function
– To secrete fluids that make up a portion (20%-40%) of the
ejaculate volume
– To provide secretions with antibacterial effect………….zinc

• Physical examination………..digital rectal examination

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 Introduction

• BPH
– A nearly ubiquitous condition in older men
– Is the most common benign neoplasm of men
older than 50 years
– occurs as a result of androgen-driven prostate
growth

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 Epidemiology
• Present as microscopic disease in many elderly males
• Peak incidence between ages 63 and 65years
• Prevalence 78% for patients at age 80 years
• Prevalence increases with advancing age
• Symptomatic disease uncommon in men younger than
50 years
• Urinary voiding symptoms……..after 60 years of age
• 20% - 30% of all male pts who live to the age of 80 years

– Require prostatectomy for severe voiding symptoms

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 Etiology
• Patient age of 40 years or more

• The stimulatory effect of androgens

• Increased alpha-adrenergic tone in smooth muscle

of the prostate and prostatic urethra

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 Etiology
• Patient age of 40 years or more

– At birth…….size of a pea and weighs 1 g

– First growth spur……..Puberty…..grow to its normal

size (15-20g)

– Second growth spur……at the age of 40 years

……continue for the rest of the person’

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 Etiology
• Effect of androgens and Increased alpha-adrenergic tone

• The prostate gland comprises three types of tissue:

– Epithelial or glandular

– Stromal or smooth muscle

– Capsule

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 Etiology
– Epithelial or glandular……produce prostatic secretion

• Growth stimulated by androgens

– Stromal or smooth muscle

• Embedded predominantly with alpha 1-adrenergic

receptors

• Compression of the urethra

• Reduction of the urethral lumen, and

• Decreased urinary bladder emptying

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 Etiology
– Capsule

• Outer shell of the prostate

• Composed of fibrous connective tissue and

smooth muscle

• Embedded with alpha 1-adrenergic receptors

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• BPH

– Precise pathophysiologic mechanisms…..not clear

– Intraprostatic dihydrotestosterone (DHT) and type II 5 α-

reductase are thought to be involved

• BPH commonly results from both:

 Static factor

gradual enlargement of the prostate and

 Dynamic factors

increase α-adrenergic tone & constrict the gland’s smooth

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muscle BPH 10
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 Clinical Presentation
• signs & symptoms categorized as obstructive or
irritative

• Symptoms vary over time

• Mild disease may stabilize whereas other patients

experience progressive disease over time

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• Obstructive signs & symptoms

– Result when dynamic and/or static factors reduce

bladder emptying

• reduced force of the urinary stream

• urinary hesitancy

• Straining

• urine dribbles out of the penis

• the bladder feels full even after voiding

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• Irritative signs and symptoms

– Result from long-standing obstruction at the bladder

neck

• Failure of the urinary bladder to store urine until

the bladder is full

– Patient experience frequency, urgency and nocturia.

• Complications of BPH include chronic renal failure, gross

hematuria, urinary incontinence, recurrent UTIs, bladder

diverticula, and bladder stones

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• Predictors of disease progression include:
– Enlarged prostate of at least 40 g
– Prostate-specific antigen (PSA) level of at least 4 ng/mL
(4 mcg/L)

• Severity of symptoms
– should be assessed by the patient using a standardized
instrument
• the American Urological Association (AUA) Symptom Scoring
Index

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 Questions to Determine the AUA Symptom Score

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 Diagnosis
• Diagnosis of BPH requires:
– Careful medical history
– Physical examination
– Objective measures of bladder emptying (e.g.,
peak and average urinary flow rate, postvoid
residual urine volume [>50ml]), and
– Laboratory tests (e.g., urinalysis, blood urea
nitrogen, and prostate-specific antigen [PSA])
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 Diagnosis
• Medication history

– prescription and nonprescription medications as well as

dietary supplements

• Transrectal ultrasound of the prostate to evaluate prostate

size

• Transrectal prostate needle biopsy to document prostate

cancer

• On digital rectal examination, the prostate is usually, but not

always, enlarged (more than 20 g), soft, smooth, and
symmetric
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 Treatment
Desired Outcomes
• Reducing or eliminating obstructive and irritative
voiding symptoms…….AUA sore reduction by at least
three points
• Slowing disease progression
• Preventing disease complications and reducing the
need for surgical intervention
• Maintaining or improving quality of life

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 General approach
• Management options for BPH include
– Watchful waiting,

– Drug therapy, and

– Surgical intervention.

• The choice depends on the severity of signs

and symptoms

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 General approach
• Watchful waiting

– For patients with mild disease and

– for those with moderate disease with only mildly

bothersome symptoms and without complications

• Involves reassessment at a periodic intervals (physician

visits every 6 to 12 months)

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• Watchful waiting
– Patients should be educated about behavior
modification such as
Fluid restriction before bedtime,

Avoiding caffeine and alcohol

Frequent emptying of the bladder, and

Avoiding drugs that exacerbate symptoms

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Algorithm for selection of treatment of BPH
based on symptom severity

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 Pharmacologic Therapy
• For patients with moderately severe symptoms

• As an interim measure for patients with severe BPH

• Effect
– interferes with the stimulatory effect of testosterone on
prostate gland enlargement (reduces the static factor) or

– relaxes prostatic smooth muscle (reduces the dynamic

factor)

– Relax bladder detrusor muscle (improving the urine

storage capacity of the bladder)

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 Pharmacologic Therapy

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 Pharmacologic Therapy

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 Pharmacologic Therapy

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 Pharmacologic Therapy

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 Pharmacologic Therapy

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 Management algorithm for BPH

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 • Initial therapy with an α-adrenergic antagonist
provides faster onset of symptom relief.

• A 5 α-reductase inhibitor is preferred as initial

therapy in patients with a prostate gland >40 g.

• Combination therapy should be considered for

symptomatic pts with a prostate gland >40 g and
PSA ≥ 1.4 ng/mL.

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 • Agents that interfere with androgen
stimulation of the prostate are not popular
because of adverse effects.
– The luteinizing hormone releasing hormone
agonists leuprolide and goserelin decrease libido
and can cause ED, gynecomastia, and hot flashes.

– The antiandrogens bicalutamide and flutamide

cause nausea, diarrhea, and hepatotoxicity.
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 α-Adrenergic Antagonists
• α-adrenergic antagonists relax the smooth
muscle in the prostate and bladder neck,
thereby increasing urinary flow rates
• Tamsulosin and doxazosin produce durable
responses for 6 and 10 yrs, respectively.
• α-adrenergic antagonists do not decrease
prostate volume or PSA levels.
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 • 2nd generation (Terazosin, doxazosin, and alfuzosin)
– antagonize peripheral vascular α 1-adrenergic receptors in
addition to those in the prostate
– adverse effects include first dose syncope, orthostatic
hypotension, and dizziness.

• Alfuzosin…..less likely to cause CV adverse effects

• slowly titrate to a maintenance dose…. 2-to7-day
intervals
• should be taken at bedtime

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 • α-Adrenergic Antagonists

– Tamsulosin and Silodosin……3rd -generation α-

adrenergic antagonist

– Selective for prostatic α1A-receptors

– Does not cause peripheral vascular smooth

muscle relaxation

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• Third generation agents preferred in patients
who
– Cannot tolerate hypotension;

– Have severe coronary artery disease, volume

depletion, cardiac arrhythmias, severe orthostasis,
or liver failure; or

– Are taking multiple antihypertensives

– Want to avoid the delay of dose titration.

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• Caution is needed to avoid potential drug
interactions.
– Tamsulosin decreases metabolism of cimetidine
and diltiazem.

– Carbamazepine and phenytoin increase

catabolism of α-adrenergic antagonists

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• Silodosin

– Requires dosage reduction in patients with a

creatinine clearance of 30 to 50m L/min

– Contraindicated in patients with severe hepatic

insufficiency or a creatinine clearance less than
30mL/min

– Interact with potent CYP3A4 inhibitors

(clarithromycin, itraconazole, ketoconazole, ritonavir,
cyclosporine)

– Causes more ejaculatory dysfunction than tamsulosin

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 5 α-Reductase Inhibitors
• 5 α-Reductase inhibitors (Dutasteride and Finasteride)

– Interfere with the stimulatory effect of testosterone

• inhibit 5a-reductase which is responsible for

intraprostatic conversion of testosterone to DHT, the
active androgen which stimulates prostate tissue growth

– slow disease progression and decrease the risk of

complications

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• Compared with α-adrenergic antagonists, 5 α-
reductase inhibitors have the disadvantages of

– Requiring 6-12 months to maximally shrink an

enlarged prostate,

– Being less likely to induce objective improvement,

and

– Causing more sexual dysfunction.

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 • Dutasteride inhibits types I & II 5 α-reductase, whereas
finasteride inhibits only type II

• Dutasteride more quickly and completely suppresses

intraprostatic DHT and decreases serum DHT by 90% (vs.
70%).

• No clinically significant difference

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 • 5 α-Reductase inhibitors preferred in patients with

– uncontrolled arrhythmias

– poorly controlled angina

– use of multiple antihypertensives, or

– inability to tolerate hypotensive effects of α-

adrenergic antagonists

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• 5 α-Reductase inhibitors reduce serum PSA levels by
50%. PSA should be measured at baseline and repeated
after 6 months.
• If PSA does not decrease by 50% after 6 mths of therapy
in a compliant pt, the pt should be evaluated for
prostate cancer.
• Both are FDA pregnancy category X.
– Pregnant and potentially pregnant women should not
handle the tablets or have contact with semen from men
receiving 5 α-reductase inhibitors.
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 SURGICAL INTERVENTION
• Prostatectomy, performed transurethrally or suprapubically,

– The gold standard

• for patients with moderate or severe symptoms and

• for all patients with complications

• Retrograde ejaculation is a complication of up to 75% of

transurethral prostatectomy procedures.

• Other complications include: bleeding, urinary incontinence

and ED.

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 EVALUATION OF THERAPEUTIC OUTCOMES

• The primary therapeutic outcome of BPH

therapy is restoring adequate urinary flow
without causing adverse effects

• Outcome depends on the patient’s perception

of effectiveness and acceptability of therapy.

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 • Objective measures of bladder emptying (e.g.,
uroflowmeter and postvoid residual urine volumes)
are also useful after 6 to 12 months of 5 α-reductase
inhibitor therapy or 6 to 12 weeks for the other
medications
• Laboratory tests (e.g., blood urea nitrogen, creatinine,
PSA) and urinalysis should be monitored regularly
• AUA score
• Annual digital rectal examination and PSA

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