1. Benign Prostatic Hypertrophy Hyperplasia Enlargement

2. BPH Benign Prostatic Hyperplasia Microscopic Macroscopic Clinical
Proliferation of stromal (fibromuscular) and epithelial (prostate secretory glands) in the transitional zone
Macroscopic
“Enlarged Prostate”; DRE, TRUS, CT, MRI
Static (epithelial/having a large blockage)
Dynamic (increased “tone” of muscle fibers)
Clinical
LUTS: storage vs. voiding vs. both (nonspecific)

3. BPH By the numbers: 14 million US men
(not all seek medical attention)
Annual cost of $4 billion per year

4. BPH Incidence and Epidemiology Most common benign tumor in men
Prevalence
20% in men 41-50
50% in men 51-60
Increase by 10% per 10 years
Familial component likely
Higher incidence in higher income & higher education
Metabolic syndrome increases likelihood of BPH

5. Anatomy

6. BPH
Evaluation:
International Prostate Symptoms Score (IPSS)/AUA Symptoms Index:
0-35 points for symptoms and severity
LUTS:
0-7 Mild
8-18 Moderate
>18 Severe

8. BPH Treatment Options: 1. Watchful waiting 2. Phytotherapeutics
3. Medical management
Alpha blockers
5 Alpha reductase inhibitors (5 ARI’s)
Phosphodiesterase inhibitors (PDE5i)
Combination therapy
4. Minimally invasive techniques
5. Surgical techniques

9. Watchful Waiting Decrease PM fluids
Decrease caffeine/ETOH/bladder irritants
Timed voids/double voids
Review Rx list and optimize
Treat constipation

10. 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.

11. 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

12. Phytotherapy Product Variability
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%

13. Phytotherapy Major Issues with phytotherapy:
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

14. Phytotherapy Saw Palmetto African Plum South African Star Grass
Stinging Nettle
Rye-Pollen Extract
Pumpkin Seeds
Other: Soy, Grape Juice, Cactus Flower, Zinc, Selenium

15. 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.

16. Alpha-Blockers Classification Nonselective: Alpha-1
Phenoxybenzamine mg BID
Alpha-1
Terazosin (Hytrin) or 10mg qDay
Doxazosin (Cardura) 4 or 8mg qDay
Alfuzosin (Uroxatral) 10mg qDay
Alpha-1a Subtype Selective
Tamsulosin (Flomax) 0.4mg qDay
Silodosin (Rapaflo) mg qDay

17. Alpha-Blockers Typical Side Effects: Orthostatic Hypotension Dizziness
Tiredness
Retrograde Ejaculation
Rhinitis
Headache
Floppy Iris Syndrome

18. 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.

19. 5 Alpha Reductase Inhibitors

20. 5 Alpha Reductase Inhibitors
DHT
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)

21. 5 Alpha Reductase Inhibitors
Low testosterone (abnormal testosterone to estradiol ratios)
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

22. 5 Alpha Reductase Inhibitors
Side Effects:
Impotence
Decreased libido
Decreased ejacualte
Breast enlargement
Hot flashes

23. 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)

24. 5 Alpha Reductase Inhibitors
Development of dutasteride (Avodart)
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.

25. 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.

26. 5 Alpha Reductase Inhibitors
REDUCE Trial
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.

27. Combination Therapy Veteran’s Affairs Cooperative Study 1996
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.

28. Combination Therapy Medical Therapy of Prostatic Symptoms (2001)
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.

29. Combination Therapy
Combination of Dutasteride and Tamsulosin (2003) by Barker et. al.
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

30. 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-physician-insurance company relationship

31. Minimally Invasive Therapy
Transurethral Microwave Procedures
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

32. Minimally Invasive Therapy
Transurethral Needle Ablation (TUNA)
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

33. Conventional Surgical Therapy
Indications for surgery
Urinary retention from BPH, medical refractory
Gross hematuria from BPH
Bladder stones
UTI’s
Renal Insufficiency/hydronephrosis

34. Conventional Surgical Therapy
Transurethral Resection of the Prostate (TURP)
“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.

35. Transurethral Incision of the Prostate (TUIP)
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

36. Transurethral Laser Surgery
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

37. Conventional Surgical Therapy
Surgical “Open” Prostatectomy
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

38. Other treatments UroLume urethral stent
Migration, worsening irritative symptoms
Encrustation and prostatic ingrowth
Intraprostatic ethanol and Botox injections
Performed via transrectal ultrasound

39. Summary Diagnosis Medical Treatment Indications for surgery
Subjective and Objective findings
Medical Treatment
Indications for surgery
Types of Surgery

40. Questions?