BPH

Dr. Jad AlSmadi, MD.,

Assistant Professor,
faculty of medicine,
The Hashemite University
 Definition

• BPH is a histologic diagnosis that refers to the proliferation

of glandular epithelial tissue, smooth muscle, and
connective tissue within the prostatic transition zone, hence
the term “stromo-glandular hyperplasia.”
• BPH is likely the result of a multifactorial process, the exact
etiology of which is unknown.
• What is clearly necessary for the development of BPH,
however, is the presence of functioning testes.
 Etiology
• I) Hormones:
• 1) Androgens: Although androgens do not cause BPH, the
development of BPH requires the presence of testicular
androgens during prostate development, puberty, and aging
• Patients castrated prior to puberty or who are affected by a
variety of genetic diseases that impair androgen action or
production do not develop BPH
• A nuclear membrane–bound enzyme steroid 5α-reductase
converts testosterone into DHT, the principal androgen
 Etiology
• I) Hormones:
• 2) Androgen Receptors (AR): The prostate, unlike other
androgen-dependent organs, maintains its ability to
respond to androgens throughout life
• Age related increases in estrogen may increase AR
expression in the aging prostate
• Intra-prostatic DHT concentrations are maintained but not
elevated in BPH
• Type 2 5α-reductase is the predominant prostatic 5α-
reductase
 Etiology

• II) Genetic and Familial Factors:

• approximately 50% of cases of men undergoing
prostatectomy for BPH at less than 60 years of age could be
attributable to an inheritable form of the disease
• Familial BPH was characterized by large prostate size, with a
mean prostate volume of 82.7 mL in men with hereditary
BPH compared with 55.5 mL in men with sporadic BPH
 Pathophysiology: Anatomy

• BPH first develops in

the periurethral
transition zone of the
prostate
• All BPH nodules
develop either in the
transition zone or in
the periurethral region
 Pathophysiology: Anatomy

• However, the
transition zone also
enlarges with age,
unrelated to the
development of
nodules
 Pathophysiology: Anatomy
• The presence of the prostatic capsule plays an important
role in the development of LUTS
• Prostatic hyperplasia increases urethral resistance,
resulting in compensatory changes in bladder function
• Obstruction-induced changes in detrusor function,
compounded by age-related changes in both bladder and
nervous system function, lead to urinary frequency,
urgency, and nocturia, the most bothersome BPH-related
complaints
 Pathophysiology
• The pathophysiology of
benign prostatic
hyperplasia (BPH)
involves complex
interactions between
urethral obstruction,
detrusor function and
dysfunction, and urine
production
Pathophysiology: Histologic Features

• Early periurethral nodules are purely stromal in character

but transition zone nodules represent proliferation of
glandular tissue
• This proliferative process leads to a tight packing of
glands within a given area as well as an increase in the
height of the lining epithelium.
• There appears to be hypertrophy of individual epithelial
cells as well
Pathophysiology: Histologic Features
• During the first 20 years of BPH development, the disease
is predominantly characterized by an increased number of
nodules
• Then a second phase of evolution occurs in which there is
a significant increase in large nodules and the size of
glandular nodules clearly predominates
• Both passive and active forces (i.e. smooth muscles) in
prostatic tissue play a major role in the pathophysiology
of BPH
Pathophysiology: Histologic Features
• Adrenergic nervous system stimulation clearly results in a
dynamic increase in prostatic urethral resistance.
Blockade of this stimulation by α-receptor blockers clearly
diminishes this response
• α1A is the most abundant adrenoreceptor subtype
present in the human prostate
• type 4 and type 5 phosphodiesterase isoenzymes in the
prostate and the detrusor muscle of the bladder implies
that phosphodiesterase inhibitors is appropriate therapies
for BPH-related LUTS
 Prevalence and Terms
• Autopsy proven histological prevalence increases starting
at age 40-45 years to reach 60% at age 60 and 80% at age
80
• BPE: benign prostatic enlargement
• BPO: benign prostatic Obstruction
• It is important to realize that not all men with BPE will
develop obstruction or BPO, just as not all men with BPH
will have BPE
 Prevalence and Terms
• BOO: Bladder Outlet Obstruction
• Obstruction may also be caused by other conditions
referred to as BOO. Thus, BPO is a subset of BOO
• The enlarged gland has been proposed to contribute to
the male LUTS complex via at least two routes:
• 1. Direct BOO/BPO from enlarged tissue (static
component)
• 2. Increased smooth muscle tone and resistance within
the enlarged gland (dynamic component)
 Prevalence and Terms

• LUTS are non-specific, occur in men and women with

similar frequency and may be caused by many conditions,
including BPE and BPO
• Complications: Urinary Tract Infections, Bladder Stones,
Urinary Incontinence, Upper Urinary Tract Deterioration
and Azotemia, Hematuria, Acute urinary retention (AUR),
Bladder Decompensation (CUR).
 Initial Evaluation (History)
• I) Complete Medical History: to assess symptoms, prior procedures that
could explain the symptoms, sexual history, use of medications, and overall
fitness and health.
• history of hematuria, UTI, diabetes, nervous system disease (e.g., Parkinson
disease or stroke), urethral stricture disease, urinary retention, and
aggravation of symptoms by cold or sinus medication
• Over-the-counter medications: drugs that impair bladder contractility
(anticholinergics) or that increase outflow resistance (sympathomimetics)
• The IPSS, a validated self-administered questionnaire, can provide clinicians
with information regarding the symptom burden patients are experiencing
 Initial Evaluation (History & P/E)

• Bladder diary and frequency-volume chart: identify patients with polyuria

• II) P/E:
• a) DRE: detect prostate or rectal malignancy, to evaluate anal sphincter
tone, presence of induration, the presence of a nodule, & establishes the
approximate size of the prostate gland;
• b) Focused neurologic examination;
• c) Examination of the external genitalia (e.g. meatal stenosis);
• d) Abdominal examination is necessary (palpation + percussion)
Initial Evaluation (Work up)

• III) Labs:
• 1. Urinalysis: to rule out other causes of LUTS (bacteria, blood, white cells,
glucose, or protein)
• 2. Serum Creatinine Measurement: Optional to exclude renal insufficiency
caused by the presence of obstructive-uropathy
• 3. Serum Prostate-Specific Antigen (PSA)
Initial Evaluation (Work up)
• III) Labs:
• 4. optional studies: PVR, uroflowmetry, and pressure flow studies:
• A) A PVR can be useful in determining a baseline ability of the bladder to
empty, detecting severe urinary retention that may not be amenable to
medical therapy, and/or indicate detrusor dysfunction
• B) Uroflowmetry: simple and risk-free, office-based procedure: Flow rates of
<10 mL/s have shown a specificity of 70%/ sensitivity of 47% for BOO
• C) Pressure flow studies: If the patient's condition is not sufficiently
suggestive of obstruction (e.g., peak urinary flow [Qmax] >10 mL/sec)
 Medical Therapy
• I) Alpha Blockers: in moderate to severe LUTS/BPH: alfuzosin, doxazosin,
silodosin, tamsulosin, or terazosin
• They are equally effective in terms of IPSS improvement, with an expected
range of improvement of 5-8 points
• The choice of specific agent should consider the differing adverse events
profiles of each:
• Terazosin and doxazosin, are non-specific alpha-1 receptor blockers that are
both approved for the treatment of hypertension
• Tamsulosin, alfuzosin, and silodosin have lower potential to cause
orthostatic hypotension and syncope
 Medical Therapy
• I) Alpha Blockers:
• Only two are alpha 1a selective: tamsulosin (10:1) and silodosin (161:1) those
drugs are more selective for the alpha 1a versus the alpha 1b receptor; are
more prone to induce Ejaculatory dysfunction (Anejaculation) (Silodocin >
tamsulosin); But less hypotensive effects.
• Younger sexually active men are more likely to discontinue due to EjD;
therefore, it would be prudent to select alpha blockers with a low incidence
of EjD
• Patients on several antihypertensives, or with orthostatic hypotension, it is
best to select an alpha blocker that exhibits minimal impact on blood
pressure (e.g., the highly selective alpha 1a blocker silodosin)
 Medical Therapy
• II) 5-Alpha Reductase Inhibitor (5-ARI):
• Both testosterone and DHT bind to the androgen receptor, although DHT
does so with greater affinity and is thus considered to be the more potent
androgenic steroid hormone.
• The T/DHT-androgen receptor complex within the nucleus of the cells of the
prostate initiates transcription and translation, thus promoting cellular
growth
• 5-ARIs act via inhibition of 5AR, leading to less available DHT in the prostate
• This, in turn, leads to a reduction in the overall androgenic growth stimulus
in the prostate, an increase in apoptosis and atrophy, and ultimately a
shrinkage of the organ ranging from 15-25% measured at six months
 Medical Therapy
• II) 5-Alpha Reductase Inhibitor (5-ARI):
• The atrophy is most pronounced in the glandular epithelial component of
the prostate, which is the source of the production and release of serum
PSA.
• Serum PSA drop by approximately 50% (and a concomitant decrease in
serum free PSA by 50%, which means that the ratio of free/total PSA
remains constant)
• The indication for treatment with 5-ARIs depends on prostate volume and
PSA threshold: Ultrasonic prostate size of >30 cc can achieved significant
results, & a minimum threshold PSA 1.5ng/dL is preferred.
 Medical Therapy
• II) 5-Alpha Reductase Inhibitor (5-ARI):
• In the prostate, and specifically in BPH tissue, type II 5-AR is far more
common than type I
• A) Finasteride: exclusively inhibits the 5-AR type II isoenzyme, reduce
serum levels of DHT by 70%, in prostate tissues by 80%, & IPSS
improvements of 3-4 points
• B) Dutasteride: inhibits both types I and II, reduce serum DHT by 95%,in
prostate tissues by 94%, & IPSS improvements of ~4.5 points
• 5-ARIs alone or in combination with alpha blockers are recommended to
prevent progression of LUTS/BPH, reduce the risks of urinary retention and
need for future prostate-related surgery
 Medical Therapy
• II) 5-Alpha Reductase Inhibitor (5-ARI):
• Side Effects: (-ve)
• A) Sexual Dysfunction: ED, libido disturbances, and ejaculatory problems
• B) Gynecomastia and breast tenderness
• C) lower risk of prostate Ca but tendency to have higher grade cancer
• +ve: reduce intraoperative bleeding and peri- or postoperative need for
blood transfusion after transurethral resection of the prostate (TURP) or
other surgical intervention for BPH.
• III) Phosphodiesterase-5 Inhibitor (PDE5): irrespective of comorbid ED
 Medical Therapy
• III) Combination Therapy
• A) 5-ARI in combination with an alpha blocker to patients with LUTS
associated with demonstrable prostatic enlargement as judged by a
prostate volume of > 30cc on imaging, a PSA >1.5ng/dL, or palpable
prostate enlargement on DRE
• B) Anticholinergic agents with an alpha blocker, to patients with moderate
to severe predominant storage LUTS
• Do not offer the combination of low-dose daily 5mg tadalafil with alpha
blockers for the treatment of LUTS/BPH as it offers no advantages in
symptom improvement over either agent alone
 Surgical Therapy

• Indications:
• renal insufficiency secondary to BPH,
• refractory urinary retention secondary to BPH,
• recurrent urinary tract infections (UTIs),
• recurrent bladder stones or gross hematuria due to BPH, and/or
• with LUTS/BPH refractory to or unwilling to use medical therapies
 Surgical Therapy
• I) TURP: remains the historical standard by which all other subsequent
surgical approaches to treatment of BPH are compared
• Successful TURP can relieve symptoms quickly with most men experiencing
significantly stronger urine flow within days of the procedure
• The risk of complications (e.g., bleeding, transfusion, hyponatremia, TURP
syndrome, death) increase with increasing prostate size and increased
duration of resection
• II) Open, laparoscopic, or robotic assisted prostatectomy, only in patients
with large (80-150 gm) to very large prostates (>150 gm)
 Surgical Therapy
• III) Transurethral Incision of the Prostate (TUIP): for patients with prostates
≤30cc as a surgical treatment of LUTS/BPH, lower rates of Retrograde
Ejaculation and need for blood transfusion than TURP.
• IV) Prostatic Urethral Lift (PUL): placement of transprostatic suture
implants. The implants pull the lumen of the prostatic urethra towards the
capsule and widen the prostatic urethral lumen
• +ve: preservation of erectile and ejaculatory function
• -ve: only average size prostate (30-80 gm), and no obstructive middle lobe
of prostate
 Surgical Therapy
• V) Laser Enucleation:
• Holmium laser enucleation of the prostate (HoLEP) or thulium laser
enucleation of the prostate (ThuLEP): prostate size-independent options
for the treatment of LUTS/BPH
• Better coagulative properties in tissue than TURP (i.e. less bleeding)
• Minimal tissue depth penetration with both holmium and thulium (0.4mm
for holmium, 0.2 mm for thulium)
• Similar outcomes when compared to TURP for the treatment of
symptomatic BPH as measured by IPSS and IPSS-QoL outcomes
 Surgical Therapy

• VI) Rezum procedure:

• sterile water vapor (steam) that is injected into the enlarged portions of the
prostate. The steam causes the prostate cells that are responsible for the
enlargement to die, which then leads to shrinking of the prostate.
• Adv.: Clinic based procedure, minimal adverse events.
• Disadv.: Sx improvement up to 2 years, high postop AUR, & only for average
sized prostates (30-80gm).
Thank You