1. Endocrinology: Benign Prostatic Hyperplasia
Courses in Therapeutics and Disease State Management

2. Epidemiology
Common benign neoplasm that affects the majority of elderly mean
BPH occurs in approximately 60% of men over 60 years of age and 78% of men over at age 80.
Peak incidence of BPH occurs between ages 63 and 65

3. Anatomy Review
Link: Representation of the anatomy of and α-adrenergic receptor distribution in the prostate, urethra, and bladder.
Normal prostate in an adult male is grams (size of a walnut)
At birth the prostate is pea size (about 1 gram) at puberty, the prostate grows to a normal size of grams and does not begin to grow again until age 40. Can grow to upto 100grams.

4. Pathophysiology
Stimulation of the concentrated α1-adrenergic receptors in the prostate causes smooth-muscle contraction
Results in compression of the urethra, reduction of the urethral lumen, and decreased urinary bladder emptying
Anatomic enlargement of the gland itself physically blocks the bladder neck
Link: Table covering Medical Treatment Options for Benign Prostatic Hyperplasia
Drug therapy targets these specific pathophysiologic processes often described as the “dynamic” and “static” factors contributing to symptoms.

5. Decreased force of stream
Symptoms
Obstructive
Irritative
Decreased force of stream
Weak flow
Hesitancy
Straining
Dribbling
Prolonged voiding
Incomplete voiding
Retention
Urgency
Frequency
Nocturia
Dysuria
Small volume
Incontinence

6. Complications Acute urinary retention Urinary tract infections
Renal impairment/Renal Failure
Hematuria when tissue growth exceeds its blood supply
Overflow urinary incontinence

7. Diagnosis and Classification
American Urological Association Prostate Symptom Score
Not at all = 0
Less than 1 time in 5 = 1
Less than half the time = 2
About half the time = 3
More than half the time = 4
Almost always = 5
Over the past month,
How often have you had the sensation of not emptying your bladders completely?
How often have you had to urinate again in less than 2 hours?
How often have you stopped and started when urinating?
How often have you found it difficult to postpone urinating ?
How often have you had a weak urinary stream?
How often have you had to push or strain to begin urinating?
How many times did you most typically get up to urinate from the time you went to bed until the time you got up in the morning?
None = 0 | Once = 1 | Twice = 2 | 3 times = 3 | 4 times = 4 | 5 times or more = 5
Score
Mild BPH = 1 to 7 | Moderate = 8 to 19 | Severe = 20 to 35
Digital rectal exam
Prostate Specific Antigen (PSA)
Urinalysis
BUN/Cr
Post Void Residuals
Urinary flow rates
Medication history
Assessment of the patient with suspected BPH involves ruling out other conditions that may be the cause or contributing to the patient’s symptoms. This involves a physical exam, careful history of the patient’s symptoms and current medication use The AUA’s Prostate symptom score is used to classify BPH symptoms as mild, moderate or severe; this guides the treatment plan

8. Treatment Approaches
Goal is to reduce symptoms and prevent complications
Link: Comparison Table of α1-Adrenergic Antagonists, 5α- Reductase Inhibitors, Phosphodiesterase Inhibitors, and Anticholinergic Agents for Benign Prostatic Hyperplasia
Watchful waiting can be initiated for pts with mild symptoms. If bothersome or moderate or severe then drug therapy is usually nitiated

9. Non-Pharmacologic Watchful waiting Lifestyle changes in all patients
Avoid medications which contribute to or exacerbate symptoms
Testosterone replacement
Adrenergic agonists (decongestants)
Anticholinergics
Diuretics
Fluid restriction at bedtime
Avoid caffeine and alcohol
Scheduled toileting
Watchful waiting is the preferred approach for patients with mild symptoms. All patients, regardless of severity should be counseled on the lifestyle changes and non-drug options for managing and preventing BPH symptoms

10. Complementary and Alternative Medicine
Saw Palmetto
Randomized placebo controlled trials have not demonstrated efficacy
Lycopene
Contradictory studies
Counsel patients to maintain vegetable rich diet
Phytosterols
Promising, but not conclusive
Diet rich in vegetables, nuts and legumes

11. Management Algorithm for Benign Prostatic Hyperplasia (BPH)
This slide provides a general summary of the pharmacologic approach to managing BPH. Alpha-blockers are generally used first line and can be used in any and all stages of symptoms.

12. First Line Therapy: Alpha 1 Blockers
Relax prostatic smooth muscle tissue, bladder neck, and urethra
Equally efficacious within a few days
All are metabolized by CYP 450 3A4
Selection of agent based on age, side effect profile, and cost

13. 2mg titrate to 8mg, XL start at 4mg
Alpha 1 Blockers
Doxazosin
Terazosin
Tamsulosin
Alfuzosin
Silodosin
Brand Name
Cardura®
Hytrin®
Flomax®
Uroxatrol®
Rapaflo®
Uroselective No
Yes
Dosing
2mg titrate to 8mg, XL start at 4mg
5mg titrate to 10mg
0.4mg (can try 0.8mg)
10mg QD
8mg (renal dose 4mg)
Timing
Bedtime
After meals*
After meals
Hypotension ++ - +
Ejaculation Disorders
+++
Rhinitis
Floppy iris syndrome
Generally, Alpha 1 Antagonists should not be used as sole treatment of hypertension in men with BPH. Retrograde ejaculation is most common with the uroselective agents and can be a troubling adverse effect. This symptom can be managed by educating men to void after ejaculation. Can typically avoid hypotension and syncope with non-selective agents by using slow weekly titrations and continued adherence. Geriatric men are more sensitive to hypotension

14. 5-Alpha Reductase Inhibitors
Shrinks enlarged prostate by blocking conversion of testosterone to dihydrotestosterone
Equally efficacious, but require at least 6 months of therapy
Effectiveness has been best demonstrated in men with significantly enlarged prostates (>40 grams)

15. 5-Alpha Reductase Inhibitors
Finasteride
Dutasteride
Brand Name
Proscar®
Avodart®
Dosing
5mg QD
0.5mg QD
Decreased Libido +
Erectile Dysfunction
Gynecomastia
Cost/day
$0.87
$3.93
Pregnant women should avoid coming into contact with tablets or the semen of men taking them
Reduce PSA by 50%, must interpret PSA in light of this.
Most effective when used in combination with alpha 1 blockers.
Use results in a 25% reduction in risk of prostate cancer; but a 27% increase in number of highly aggressive tumors among those detected

16. Other Therapies Phosphodiesterase-5 Inhibitors Antimuscarinics
October 2011, the FDA approved tadalafil (Cialis®) for the treatment of symptoms related to BPH.
Not first line, but option for men with BPH and ED
Hypotension risk?
Antimuscarinics
Adjunctive for some men with urge incontinence
Not for patients with high post-void residuals
Small crossover studies in combo with tamsulosin or afluzosin demonstrate improvement in both BPH and ED and did not show increased risk of hypotension. However, these studies were conducted with younger men. Caution is warranted in their combined use in geriatric men.

17. Surgical Therapy
Typically reserved for men with complications, severe symptoms unresponsive to optimal pharmacotherapy, or those who prefer surgery
Greatly improves symptoms but high complication rates
Transurethral resection of the prostate (TURP)
Open prostatectomy
Both procedures can result in retrograde ejaculation, urinary incontinence, and erectile dysfunction. These procedures are generally ineffective towards the irritative voiding symptoms.

18. The Role of the Pharmacist
Selecting an agent and appropriate dose
Patient education on lifestyle modifications
Counseling on correct administration and management of adverse effects
Monitoring use of OTC and prescription drugs that may exacerbate BPH
Link: Table on Monitoring of Drugs Used in Treatment of Benign Prostatic Hyperplasia
Link: Table on Dosing of Drugs Used in Treatment of Benign Prostatic Hyperplasia