Benign Prostatic
Hypertrophy
Hyperplasia
Enlargement
BPH
Benign Prostatic Hyperplasia

Microscopic
Proliferation of stromal (fibromuscular) and
epithelial (prostate secretory glands) in the
transitional zone
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Macroscopic
“Enlarged Prostate”; DRE, TRUS, CT, MRI
Static (epithelial/having a large blockage)
Dynamic (increased “tone” of muscle fibers)
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Clinical
LUTS: storage vs. voiding vs. both (nonspecific)
BPH
By the numbers:
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14 million US men
(not all seek medical attention)
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Annual cost of $4 billion per year
BPH
Incidence and Epidemiology
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Most common benign tumor in men
Prevalence
20% in men 41-50
50% in men 51-60
Increase by 10% per 10 years
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Familial component likely
Higher incidence in higher income & higher education
Metabolic syndrome increases likelihood of BPH
Anatomy
BPH
Evaluation:

International Prostate Symptoms Score
(IPSS)/AUA Symptoms Index:
0-35 points for symptoms and severity
LUTS:
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0-7 Mild
8-18 Moderate
>18 Severe
BPH
Treatment Options:
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1. Watchful waiting
2. Phytotherapeutics
3. Medical management
Alpha blockers
5 Alpha reductase inhibitors (5 ARI’s)
Phosphodiesterase inhibitors (PDE5i)
Combination therapy
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4. Minimally invasive techniques
5. Surgical techniques
Watchful Waiting
Decrease PM fluids
Decrease caffeine/ETOH/bladder irritants
Timed voids/double voids
Review Rx list and optimize
Treat constipation
Phytotherapy
Phytotherapeutic agents are standardized
herbal preparations consisting of complex
mixtures of one or more plants which
contain as active ingredients plant parts or
plant material in the crude or processed
state.
Last year, the US herbal supplement
market was $7.4 billion.
Phytotherapy
Phytotherapeutic agents are commonly
prescribed in Europe for LUTS, and in the
US 30-90% of patients seen by urologists
for BPH/LUTS may be taking them
The US market for dietary supplements to
treat LUTS or just “to keep the prostate
healthy” is around $1.5 billion per year
Phytotherapy
Product Variability
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Evaluation and use of these products are
complicated by variations in the plants
themselves as well as the process to extract
the desired components.
Study (Feifer et al., 2002), showed that 3/6
samples of saw palmetto was less than 20%
of the amount stated on the label and two of
these had less than 5%
Phytotherapy
Major Issues with phytotherapy:
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1. The clinical benefits of phytotherapeutic agents for
BPH are still uncertain
2. Saw Palmetto is the most widely used nutraceutical
for BPH
3. The mechanism of action of phytotherapeutic agents
on BPH are thought to be weakly similar to finasteride,
decreasing testosterone’s effects on the prostate
4. There is significant interbrand and intrabrand
variability
5. The “presumed” safety of these products has never
been fully confirmed
Rare scientific head to head comparisons with
standard treatments
Phytotherapy
Saw Palmetto
African Plum
South African Star Grass
Stinging Nettle
Rye-Pollen Extract
Pumpkin Seeds
Other: Soy, Grape Juice, Cactus Flower,
Zinc, Selenium
Alpha-Blockers
Basis of therapy:

The dynamic (increased muscle tone) part of BPH
A component of BPH and bladder obstruction is
mediated by alpha adrenergic receptors associated
with prostatic smooth muscle.
Alpha-Blockers
Classification

Nonselective:
Phenoxybenzamine

10mg BID
Alpha-1
Terazosin (Hytrin)
5 or 10mg qDay
Doxazosin (Cardura) 4 or 8mg qDay
Alfuzosin (Uroxatral) 10mg qDay

Alpha-1a Subtype Selective
Tamsulosin (Flomax) 0.4mg qDay
Silodosin (Rapaflo)
8mg qDay
Alpha-Blockers
Typical Side Effects:
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Orthostatic Hypotension
Dizziness
Tiredness
Retrograde Ejaculation
Rhinitis
Headache
Floppy Iris Syndrome
5 Alpha Reductase Inhibitors
Development

Experimental studies:
Testosterone production or function is inhibited in
men castrated before puberty
These same men were noted to have abnormal
prostate development
Later determined that embryonic development of
the prostate is dependent on the androgen DHT,
which is converted from testosterone by the
enzyme, 5 alpha reductase.
5 Alpha Reductase Inhibitors
5 Alpha Reductase Inhibitors
DHT

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Provides the major growth stimulus for
prostatic tissue due to its 4-5 fold higher
affinity for the prostatic androgen receptor
compared to testosterone
Other anti-androgenic agents have been
investigated, but most lead to decreased
levels of testosterone as well as DHT
(think Lupron in prostate cancer)
5 Alpha Reductase Inhibitors
Low testosterone (abnormal testosterone
to estradiol ratios)

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Intolerable sexual side effects: erectile
dysfunction, decreased libido
Also: gynecomastia and hot flashes
Thus, the development of 5 ARI’s to
improve LUTS without sexual side effects
associated with reduction in testosterone
levels
5 Alpha Reductase Inhibitors
Side Effects:
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Impotence
Decreased libido
Decreased ejacualte
Breast enlargement
Hot flashes
5 Alpha Reductase Inhibitors
Finasteride (Proscar)

Results in 80-90% reduction of type II 5 alpha
reductase within the prostate.
Decreased intraprostatic DHT there is reduction of
epithelial (static) glandular tissue volume with
resultant decrease in total gland volume (~20-30%)

Note finasteride (static) vs Flomax (dynamic)
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5 Alpha Reductase Inhibitors
Development of dutasteride (Avodart)
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Hypothesis that inhibition of both Type I &
Type II 5 alpha reductase may increase
efficacy of tx of BPH
Thus, dutasteride (second generation) that
inhibits both types
In comparison to finasteride, it suppresses
DHT production by 93% (finasteride 70%, but
objective and subjective urinary tract effects
are the same.
5 Alpha Reductase Inhibitors
Prostate Cancer Prevention Trial (PCPT)

Results:
Prostate cancer was detected in 24.4% of controls
and only 18.4% of treated patients
First time a treatment was shown to prevent or
delay the appearance of prostate cancer
However, also noted that the proportion of Gleason
7 or higher tumors was greater in the finasteride
group.
5 Alpha Reductase Inhibitors
REDUCE Trial
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Chemoprevention for prostate cancer
8,200 men
4 year trial
Double-blind placebo
23% reduction in risk of prostate cancer
No increased risk of aggressive tumors like
PCPT.
Combination Therapy
Veteran’s Affairs Cooperative Study 1996
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Placebo, Finasteride, Terazosin, and Combo
1229 patients, Double Blind Placebo Controlled
Showed significant improvement in AUA symptom
scores in terazosin and combo therapy groups.
Since they had similar improvements, it was
determined that the finasteride had no benefit
Thus, alpha blockade (Flomax) had superiority over
finasteride at 1 year.
Combination Therapy
Medical Therapy of Prostatic Symptoms
(2001)
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Can medical therapy prevent or delay the
progression of BPH in the long term.
5 years out: Combination of Doxazosin and
Finasteride exerts a clinically relevant,
positive effect on rates of disease
progression.
Combination Therapy
Combination of Dutasteride and Tamsulosin
(2003) by Barker et. al.
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Combo for 24 weeks, then withdrew the Tamsulosin
for 12 weeks.
Patients with IPSS score <20: 84% continued
monotherapy without worsening of symptoms
IPSS scores >20: 42% had worsening of symptoms
Concluded that combo therapy allows alpha blockers
to provide more rapid relief and 5 alpha reductase
inhibitors for long-term treatment.
Start with combo, patients with less severe symptoms
can stop alpha blocker; more severe continue combo
Phosphodiesterase 5 Inhibitors
Cialis 5mg daily
Decreases the smooth muscle tone in the
bladder, prostate and urethra (like Flomax)
SE include back/muscle aches, GERD,
and headaches and strengthening of
erections.
Good combination Rx
Nice for ED, not for the patient-physicianinsurance company relationship
Minimally Invasive Therapy
Transurethral Microwave Procedures
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Microwaves are sent through a catheter to at
least 111 degrees
Cooling system protects the urinary tract
Outpatient
Reduces: frequency, urgency, straining, and
intermittent flow
Does NOT correct incomplete emptying
Long term effects are still unknown
Minimally Invasive Therapy
Transurethral Needle Ablation (TUNA)
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Low-level radiofrequency energy through twin
needles to burn away selected areas of the
prostate
Shields protect the urethra
Improves urine flow and relieves symptoms
Conventional Surgical Therapy
Indications for surgery
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Urinary retention from BPH, medical refractory
Gross hematuria from BPH
Bladder stones
UTI’s
Renal Insufficiency/hydronephrosis
Conventional Surgical Therapy
Transurethral Resection of the Prostate
(TURP)
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“Gold Standard”
60-90 minutes
General or Spinal
Wire Loop
Complications: Infertility, UTI, Bladder stones, gross
hematuria, retrograde ejaculation, urethral strictures
or bladder neck contractures.
Transurethral Incision of the Prostate (TUIP)
Transurethral Incision
of the Prostate (TUIP)
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Variation of TURP
Instead of removing
prostate tissue, small cuts
are made in bladder neck
Shorter operative time
Good for short glands, men
who have had radiation
therapy and are at risk for
incontinence or wish to
preserve fertility
Transurethral Laser Surgery
Transurethral Laser
Surgery
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Usually a side-firing laser is
placed through cystoscope
Holmium, Greenlight/PVP,
Thullium
Laser destroys/vaporizes
prostatic tissue
As good as a TURP with
similar potential
complications
Conventional Surgical Therapy
Surgical “Open”
Prostatectomy
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In cases where the
prostate is too large
for a TURP or if the
bladder has very large
stones
Open incision or with
DaVinci Robot
Opens the prostatic
capsule and scoops
out the prostatic tissue
Other treatments
UroLume urethral stent
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Migration, worsening irritative symptoms
Encrustation and prostatic ingrowth
Intraprostatic ethanol and Botox injections
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Performed via transrectal ultrasound
Summary
Diagnosis

Subjective and Objective findings
Medical Treatment
Indications for surgery
Types of Surgery
Questions?