Benign Prostatic Hyperplasia

Introduction.
• BPH is present as histologic disease in many elderly males

• Occurs as a result of androgen-driven prostate growth.

• Two chief etiologic factors for BPH include advanced patient

age and the stimulatory effect of androgens.

• The disease can be characterized by three stages: BPH, benign

prostatic enlargement (BPE), and benign prostatic obstruction
(BPO)
 Cont…

• The peak incidence of clinical BPH occurs between ages 63 and 65

years.

• Symptomatic disease is uncommon in men younger than 50 years,

but some urinary voiding symptoms are present by the time men turn
60 years.
 Prostate physiology
• The prostate gland comprises three types of tissue
• Epithelial tissue(glandular tissue)
• Stromal tissue(smooth muscle tissue)
• The capsule, or outer shell of the prostate, (fibrous connective
tissue and smooth muscle)
• Both stromal tissue and capsule are embedded with α1-adrenergic
receptors.
• The precise pathophysiologic mechanisms that cause BPH are not
clear.
 Pathophysiology
• The precise pathophysiologic mechanisms that cause BPH are not
clear.

• Both intraprostatic dihydrotestosterone (DHT) and type II 5α-

reductase are thought to be involved

• BPH commonly results from both:

• Static (gradual enlargement of the prostate) and

• Dynamic (agents or situations that increase α-adrenergic tone and

constrict the gland’s smooth muscle) factors.
 Cont….
• Drugs that can exacerbate symptoms:

• testosterone

• α-adrenergic agonists and

• anticholinergic agents

• antihistamines,

• phenothiazines, TCAs, anticholinergic antispasmodics, and anti-

Parkinson’s disease
 Clinical presentation

• All symptoms of BPH can be divided into two categories:

obstructive and irritative.
 Obstructive symptoms(prostatism or bladder outlet obstruction),
result when dynamic and/or static factors reduce bladder
emptying.
 Patients experience:
 urinary hesitancy
 urine dribbles out of the penis
 the bladder feels full even after voiding
 Clinical presentation
• Irritative signs and symptoms result from long-standing obstruction
at the bladder neck.
• Patients experience:
– frequency,
– urgency, and
– nocturia.
Symptoms vary over time.
Mild disease may stabilize whereas other patients experience
progressive disease over time.
• Complications: chronic kidney disease, gross hematuria, urinary
incontinence, recurrent urinary tract infection, bladder diverticula,
and bladder stones.
Categories of BPH Disease Severity Based on Symptoms
and Signs
 DIAGNOSIS
• Diagnosis of BPH requires a careful:
– Medical history
– Physical examination
– Objective measures of bladder emptying
• peak and average urinary flow rate
• Post void residual urine volume
– laboratory tests
• urinalysis
• blood urea nitrogen
• prostate-specific antigen [PSA].
 Diagnosis…
• Medication history should include all prescription and
nonprescription medications as well as dietary supplements.

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

always, enlarged (more than 20 g), soft, smooth, and
symmetric.
 Desired Outcomes
 Slowing disease progression.

 Preventing disease complications and reducing the need for surgical

intervention.

 Avoiding or minimizing adverse treatment effects.

 Providing economical therapy.

 Maintaining or improving quality of life.

 Treatment

Management options for BPH include watchful waiting, drug

therapy, and surgical intervention.

• The choice depends on the severity of signs and Symptoms

 Treatment…
• Watchful waiting:
– Mild disease
– Moderate disease + mildly bothersome symptoms -
complications
• Watchful waiting involves reassessment at yearly intervals.
• Patients should be educated about behavior modification
such as:
– Fluid restriction before bedtime
– Avoiding caffeine and alcohol
– Frequent emptying of the bladder
– Avoiding drugs that exacerbate symptoms
 Pharmacologic therapy
• Pharmacologic therapy:
– Moderately severe BPH
– Interim measure for severe BPH
• Drug therapy for BPH can be categorized into three types:
– Agents that relax prostatic smooth muscle (reducing the dynamic factor),
– Agents that interfere with testosterone’s stimulatory effect on prostate
– Gland enlargement (reducing the static factor), and
– Agents that relax bladder detrusor muscle (improving the urine storage
capacity of the bladder)
• Initial therapy with an α-adrenergic antagonist provides faster onset
of symptom relief.
• A 5α-reductase inhibitor is preferred as initial therapy in patients with
a prostate gland >40 g.
 Cont….

• For patients with both erectile dysfunction and BPH, a

phosphodiesterase inhibitor alone or in combination with an α-

adrenergic antagonist may be used.

• For patients with LUTS with a predominance of irritative voiding

symptoms, an anticholinergic agent could be added to an existing

drug regimen for BPH

Pharmacologic therapy…
 Pharmacologic therapy…
• Combination therapy should be considered for symptomatic patients with a
prostate gland >40 g and PSA ≥1.4 ng/mL.
• Agents that interfere with androgen stimulation of the prostate are not
popular because of adverse effects.
• The luteinizing hormone-RH agonists leuprolide and goserelin decrease
libido and can cause:
– erectile dysfunction
– gynecomastia
– hot flashes
• The antiandrogens bicalutamide and flutamide cause:
– nausea, diarrhea, and hepatotoxicity.
 α-Adrenergic Antagonists
• Three generations of α-adrenergic antagonists have been used to treat
BPH.
• They all relax smooth muscle in the prostate and bladder neck.
• first-generation have been replaced by the second-generation and
third-generation uroselective postsynaptic α1A-adrenergic
antagonists.
• These agents generally improve the
– AUA Symptom Score by 30% to 40%,
– decreasing the AUA Symptom Index by three to six points, within 2 to 6 weeks,
– increase urinary flow rate by 2 to 3 mL/s in 60% to 70% of treated patients;
– reduce PVR urine volume.
 Cont…
• Modified- or extended-release formulations and third-generation

• α1A-adrenergic antagonists produce a lower prevalence of

hypotension than immediate-release,

• Second-generation agents. α1A-Adrenergic antagonists are more

likely to produce ejaculation disorders than α1-adrenergic
antagonists.
 α-Adrenergic Antagonists

• Tamsulosin and doxazosin produce durable responses for 6 and 10

years, respectively.

• α-Adrenergic antagonists do not decrease prostate volume or PSA

levels.

• Terazosin, doxazosin, and alfuzosin are second-generation α-

adrenergic antagonists.

– They antagonize peripheral vascular α1-adrenergic receptors in

addition to those in the prostate.
 α-Adrenergic Antagonists…

– Therefore, their adverse effects include first-dose syncope,

orthostatic hypotension, and dizziness.

• Alfuzosin is less likely to cause cardiovascular adverse effects than

other second-generation agents.

• Patients :

– should be slowly titrated to a maintenance dose

– should take these drugs at bedtime to minimize orthostatic

hypotension and first-dose syncope with terazosin and doxazosin.
α-Adrenergic Antagonists…
 α-Adrenergic Antagonists…
• Tamsulosin and silodosin, the only third-generation α-adrenergic
antagonist, is selective for prostatic α1A-receptors.
• Therefore, tamsulosin does not cause peripheral vascular smooth
muscle relaxation.
• Tamsulosin is a good choice for patients who:
– cannot tolerate hypotension
– have severe coronary artery disease
– Have volume depletion
– Have cardiac arrhythmias,
– Have severe orthostasis, or
– have liver failure; or
– are taking multiple antihypertensives.
 α-Adrenergic Antagonists…
• Tamsulosin is also suitable for patients who want to avoid the
delay of dose titration.

• Tamsulosin decreases metabolism of cimetidine and

diltiazem.

• Carbamazepine and phenytoin increase catabolism of α-

adrenergic antagonists.
 5α-Reductase Inhibitors (Dutasteride
and Finasteride)
• 5α-Reductase inhibitors interfere with the stimulatory effect of
testosterone.
• These agents slow disease progression and decrease the risk of
complications.
• Compared with α-adrenergic antagonists, 5α-reductase inhibitors:
– have the disadvantages of requiring 6 months to maximally
shrink an enlarged prostate
– being less likely to induce objective improvement, and
– causing more sexual dysfunction.
 5α-Reductase Inhibitors
(Dutasteride and Finasteride)…
• Whether the pharmacodynamic advantages of dutasteride confer
clinical advantages over finasteride is unknown.

• Dutasteride inhibits types I and II 5α-reductase, whereas finasteride

inhibits only type II.

• Dutasteride more quickly and completely suppresses intraprostatic

DHT (vs. 80% to 90% for finasteride) and decreases serum DHT by
90% (versus 70%).
 5α-Reductase Inhibitors
(Dutasteride and Finasteride)…
• 5α-Reductase inhibitors may be preferred in patients with:

– uncontrolled arrhythmias,

– poorly controlled angina,

– use of multiple antihypertensives, or

– inability to tolerate hypotensive effects of α-adrenergic

antagonists.

• 5α-Reductase inhibitors reduce serum PSA levels by 50%.

 5α-Reductase Inhibitors
(Dutasteride and Finasteride)…
• PSA should be measured at baseline and repeated after 6 months.

• If PSA does not decrease by 50% after 6 months of therapy in a

compliant patient, the patient should be evaluated for prostate
cancer.

• 5α-Reductase inhibitors are in FDA pregnancy category X.

• Pregnant and potentially pregnant women should not handle the

tablets or have contact with semen from men receiving 5α-reductase
inhibitors
 Surgical intervention
• Prostatectomy, performed transurethrally or suprapubically, is
the gold standard treatment for:
– patients with moderate or severe symptoms of BPH
– all patients with complications.

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

transurethral prostatectomy procedures.
• Other complications seen in 2% to 15% of patients include:
– bleeding, urinary incontinence, and erectile dysfunction.
 PHYTOTHERAPY

• Although widely used in Europe for BPH, phytotherapy with

products such as saw palmetto berry (Serenoa repens), stinging
nettle (Urtica dioica), and African plum (Pygeum africanum) should
be avoided.

• Studies of these herbal medicines are inconclusive, and the purity

of available products is questionable.
 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.

• The American Urological Association Symptom Score is a

validated standardized instrument that can be used to assess patient
quality of life.
Evaluation of therapeutic outcomes…

• Objective measures of bladder emptying (e.g., uroflowmeter and

postvoid residual urine volumes) are also useful:

– after 6 to 12 months of 5α-reductase inhibitor therapy or

– 3 to 4 weeks of α-adrenergic antagonist therapy.

• Laboratory tests (e.g., blood urea nitrogen, creatinine, PSA) and

urinalysis should be monitored regularly.

• In addition, patients should have an annual digital rectal

examination.