Benign prostatic hyperplasia (BPH) is a common condition in aging men that involves the noncancerous enlargement of the prostate gland. BPH can cause lower urinary tract symptoms by compressing the urethra. Treatment options include medications to shrink the prostate or relax the urethra, such as alpha-blockers and 5-alpha reductase inhibitors. Surgery is considered if medications do not provide relief or for men with more severe complications. Managing BPH aims to improve symptoms, prevent disease progression, and reduce the risk of future complications through watchful waiting, medications, or surgery if needed.
2. Introduction
The prostate is a heart-shaped, chestnut-sized organ
Encircles the portion of the proximal urethra
Is composed of glandular/Epithelial and muscle /stromal
tissues
The prostate produces secretions which are part of the
ejaculate
BPH is the most common benign neoplasm in males
BPH can produce LUT voiding symptoms
Drugs are common modes of treatment to reduce
symptoms
3. Epidemiology
BPH is present as microscopic disease in many
elderly males.
The prevalence increases with advancing pt age.
8 % of males 40 years of age and 35% of men 60-
69 yrs have voiding symptoms consistent with
BPH
20% to 30%(>=80 yrs males) will require a
prostatectomy for severe voiding symptoms
4. Etiology
Two chief etiologic factors for BPH include
advanced patient age and the stimulatory
effect of androgens.
I. Prior to 40 years of age, the prostate in men is
approximately 15 g to 20 g. However, in men
who have reached 40 years of age, the
prostate undergoes a growth spurt, which
continues as men advance in age. BPH can
result in clinically symptomatic LUTS.
5. II. The testes and adrenal glands produce 90%
and 10%, respectively, of circulating
testosterone. Testosterone enters prostate
cells, where predominantly Type II 5α-
reductase converts testosterone to
dihydrotestosterone, which combines with a
cytoplasmic receptor. The complex enters the
nucleus and induces changes in protein
synthesis that promote glandular tissue growth
of the prostate.
6. The prostate is composed of two types of
tissue:
A. glandular or epithelial tissue, which
produces prostatic secretions, including
prostate-specific antigen (PSA), and
B. muscle or stromal tissue, which can
contract around the urethra and bladder
outlet when stimulated.
7. In an enlarged prostate, the epithelial to stromal
tissue ratio is 1:5. Whereas androgens stimulate
glandular tissue growth, they have no direct effect on
stromal tissue.
Stromal tissue growth may be stimulated by
estrogen, which is derived from peripheral tissue
conversion of testosterone.
Stromal tissue is innervated by α1A-adrenergic
receptors. When stimulated, prostatic stroma
contracts around the urethra, narrowing the urethra
and causing obstructive voiding symptoms.
8. Pathophysiology
Pathophysiologic mechanism to clinical manifestation:
1. Static : anatomic obstruction of the bladder neck caused by
an enlarged prostate gland.
2. Dynamic: over stimulation of α1A-adrenergic receptors
reduces the caliber of the urethral lumen.
3. Detrusor: bladder detrusor muscle hypertrophy in response
to prolonged bladder outlet obstruction.
9. The hypertrophic detrusor muscle becomes
irritable, contracting abnormally in response to
small amounts of urine in the bladder.
This causes storage voiding symptoms (urinary
frequency, nocturia, urgency, or urinary
incontinence).
If obstruction is not treated, the bladder muscle
will decompensate and be unable to empty
completely; postvoid residual urine volume
(PVR) will increase.
10. Fig. Flow of urine is interrupted by compression from a prostate that has
enlarged from normal size. In this diagram, the ureters and bladder are
dilated by backed-up urine
11. Clinical Presentation
1. Obstructive: urinary hesitancy, decreased force of urinary
stream, straining to void, and intermittency
2. Irritative: urinary frequency, nocturia, and urgency with or
without incontinence
3. Postmicturition: dribbling, incomplete bladder emptying
The natural history of untreated BPH is unclear in pts with
mild symptoms
In pts with moderate to severe symptoms, the likelihood of
developing complications of BPH is higher
Predictors of disease progression include an enlarged prostate of at
least 40 g or PSA of 1.6 ng/mL (1.6 mcg/L) or greater.
12.
13. Diagnosis
Diagnosis of BPH requires a careful medical history,
physical examination, objective measures of bladder
emptying
All prescription and nonprescription medications as
well as dietary supplements must be quested
18. TREATMENT
Desired Outcome
Slowing disease progression
Normalizing serum BUN and creatinine
Preventing complications and reducing the need for surgery
Avoiding or minimizing adverse treatment effects
Providing economical therapy
Maintaining or improving quality of life
19.
20. Non-Pharmacological Therapy
Discontinue or minimize oral fluid intake after 6 P.M.
Void before going to bed
Take the diuretic in the morning, not the evening
Caution on worsening medications
21.
22. PHARMACOLOGIC THERAPY
For pts with moderately severe BPH
Mechanisms:
Reduce prostate gland enlargement => Reduces
the static factor
Target is on androgens
Relaxes prostatic smooth muscle => Reduces the
dynamic factor
Target is on α1 receptors
23.
24. α-adrenergic antagonist for:
Faster onset of symptom relief
A 5 α-reductase inhibitor for:
Prostate gland >40 g
Combination therapy for:
Prostate gland >40 g and PSA ≥ 4 ng/mL
25. Leuprolide and goserelin decrease libido and
can cause erectile dysfunction, gynecomastia,
and hot flashes.
The antiandrogens bicalutamide and flutamide
cause nausea, diarrhea, and hepatotoxicity
26. α-Adrenergic Antagonists
α-Adrenergic antagonists:
Relax the smooth muscle in the prostate and bladder
neck
Increase urinary flow rates by 2 to 3 mL/sec in 60% to
70% of pts
Reducing postvoid residual urine volumes(to <50 ml)
Do not decrease prostate volume or PSA levels
All α 1-adrenergic antagonists are considered equally
effective in relieving symptoms
27. Tamsulosin & Doxazosin give durable responses for 6 &10 yrs
Terazosin, Doxazosin, and Alfuzosin belongs to 2nd- generation:
Cause first dose syncope, orthostatic hypotension, and
dizziness
Alfuzosin is less likely to cause cardiovascular ADR
Slow titration and bedtime administration to minimize ADR
Tamsulosin and Silodocin belongs to third-generation:
Does not cause peripheral vascular smooth muscle relaxation
28. Tamsulosin is a good choice for:
Pts who can not tolerate hypotension;
Pts 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
29. Uroselectivity
Pharmacologic uroselectivity refers to preferential inhibition of
α1A-receptors, which comprise 70% of α1 receptors in the
prostatic stroma, prostatic urethra, and bladder neck.
Pharmacologically uroselective α1A-adrenergic antagonists,
tamsulosin and silodosin, have the potential to produce less
hypotension than other α1-adrenergic antagonists, because the
former have a lower propensity to antagonize α1B-adrenergic
receptors in the peripheral vasculature.
Silodosin has significantly greater α1A-adrenergic selectivity
than tamsulosin and is preferred when a patient has minimal
tolerance for any blood pressure lowering adverse effects.
30. Although not a pharmacologically uroselective
α1Aadrenergic antagonist, alfuzosin is only available
in an extended-release formulation and is prescribed
as a fixed dose with no up-titration. As a result,
alfuzosin is considered functionally uroselective
Uroselectivity is a dose-related phenomena. Large
daily doses of tamsulosin, silodosin, or alfuzosin may
cause loss of uroselectivity, with resultant
hypotension and dizziness in some patients
31. 5 α-Reductase Inhibitors
5 α-Reductase inhibitors:
Interfere with the stimulatory effect of testosterone
Slow disease progression and decrease the risk of complications
Require 6 months to maximally shrink(15-25%) an enlarged
prostate
Cause more sexual dysfunction
Dutasteride inhibits types I and II 5 α-reductase
More quickly and completely suppresses intraprostatic DHT by
90%
Decreases serum DHT by 90%
Finasteride inhibits only type II 5 α-reductase
32. They may be preferred in pts with CVD
They reduce serum PSA levels by 50% with in 6 month
of Rx
If not, the pt should be evaluated for prostate cancer
Sexual dysfunction, including decreased libido, erectile
dysfunction, ejaculation disorders, and gynecomastia,
occurs in 5% to 15% of treated patients.
The frequency of sexual dysfunction peaks generally 1
year after the start of treatment,
34. Surgical intervention
Prostatectomy for pts with moderate or severe symptoms of BPH and for all
pts with complications (gold standard)
Types
Complications:
Retrograde ejaculation (75% of transurethral prostatectomy)
Bleeding, urinary incontinence, and erectile dysfunction (2% to 15%)
Transurethral Suprapubical
35. Note
Drug treatment is expected to decrease the
American Urological Association (AUA)
Symptom Score by 30% to 50% (or at least
by three or more points),improve peak and
mean urinary flow rate by at least 1 to 3
mL/s, and decrease PVR to normal (< 50 mL
total) when compared with pretreatment
baseline values.
36. Note…
For patients with mild symptoms (AUA Symptom
Score of 7 or less) that the patient does not consider
to be bothersome, watchful waiting is a reasonable
approach to treatment.
The patient is instructed to schedule return visits to
the clinician every 6 to 12 months.
At each visit, the patient’s symptoms are reassessed
using the AUA Symptom Scoring Index, and results
are compared against the baseline
37. Note…
pts with moderate to severe symptoms benefited from
a combination of α-adrenergic antagonist plus 5α-
reductase inhibitor drug therapy.
Specifically, the use of doxazosin plus finasteride was
more effective than doxazosin alone or finasteride
alone in relieving symptoms, reducing the need for
prostatectomy, and decreasing the incidence of BPH
complications in patients at highest risk of developing
disease complications (i.e., those with prostate size of
at least 40 g)
38. Note…
If the patient has irritative voiding symptoms
anticholinergic agents should be added on
the pharmacologic treatment of BPH
If the patient has erectile dysfunction add
tadalafil
39. Note….
Surgery is indicated for patients who are at
risk of disease progression
– those with large prostates [larger than 40
g) and PSA higher than 1.6 ng/mL (1.6
mcg/L),
– have moderate-to-severe symptoms and
who are unresponsive to or intolerant of
drug treatment, or
– have complications of BPH
40. Note…
Although it is potentially curative, surgery can
result in significant morbidity, including erectile
dysfunction, retrograde ejaculation, urinary
incontinence, bleeding, or urinary tract
infection.
The gold standard is a prostatectomy, which
can be performed transurethrally or as an
open surgical procedure, which can be
performed suprapubically or retropubically.
41. To avoid complications of prostatectomy, minimally
invasive surgical procedures, such
as transurethral incision of the prostate, transurethral
needle ablation, or transurethral laser ablation, are
options.
However, minimally invasive surgical procedures are
associated with a higher reoperation rate than a
prostatectomy.
Drug treatment is used in pts with severe disease
when the pt refuses surgery or when the pt is not a
surgical candidate because of concomitant diseases.
42. Evaluation outcomes
The AUA Symptom Score can be used to assess
patient quality of life.
Bladder emptying measurements are also useful:
After 6 to 12 months of 5 α-reductase inhibitor therapy or
3 to 4 weeks of α-adrenergic antagonist therapy
Laboratory tests (e.g., BUN, SCr, PSA) and urinalysis
should be monitored regularly
Pts should have an annual digital rectal examination
Monitor and manage ADR on every Visit
Editor's Notes
DRE to check for an enlarged prostate (> 15–20 g [0.5–0.7 oz]). Nodules, induration, or asymmetry may be due to prostate cancer or some other disease.
The diagnosis does not require histologic confirmation. A prostate biopsy is only warranted if there is concern about prostate cancer such as an asymmetric or nodular gland on digital rectal examination (DRE) or an increased or rising prostate-specific antigen (PSA) level.