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7/27/2019 Benign prostatic hyperplasia.doc
http://slidepdf.com/reader/full/benign-prostatic-hyperplasiadoc 1/11
Benign prostatic hyperplasia (BPH), also called benign enlargement of the
prostate (BEP),adenofibromyomatous hyperplasia and benign prostatic
hypertrophy (technically incorrect usage), is a benign increase in size of the prostate.
BPH involves hyperplasia of prostatic stromal and epithelial cells, resulting in the formation of large,
fairly discrete nodules in the periurethral region (transition zone) of the prostate. [1 !hen sufficiently
large, the nodules impinge on theurethra and increase resistance to flo" of urine from the bladder.
#his is commonly referred to as $obstruction,$ although the urethral lumen is no less patent, only
compressed. %esistance to urine flo" re&uires the bladder to "or' harder during voiding, possibly
leading to progressive hypertrophy, instability, or "ea'ness (atony) of the bladder muscle.
lthough prostate specific antigen levels may be elevated in these patients because of increased
organ volume and inflammation due to urinary tract infections, BPH does not lead to cancer or
increase the ris' of cancer.[
BPH involves hyperplasia (an increase in the number of cells) rather than hypertrophy (a gro"th inthe size of individual cells), but the t"o terms are often used interchangeably, even
amongst urologists.[*
denomatous prostatic gro"th is believed to begin at appro+imately age * years. n estimated
- of men havehistologic evidence of BPH by age - years and /- by age 0 years in 23-
of these men, BPH becomes clinically significant. [2
Contents
[hide
• 1 4igns and symptoms• 5auses
• * Pathophysiology
• 2 6iagnosis
• - 7anagement
o -.1 8ifestyle
o -. 9oiding position
o
-.* 7edications
o -.2 7inimally invasive therapies
o -.- 4urgery
o -.: lternative medicine
• : ;pidemiology
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• / %eferences
• 0 <urther reading
• = ;+ternal lin's
Signs and symptoms[edit
Benign prostatic hyperplasia symptoms are classified as storage or voiding.
4torage symptoms include urinary fre&uency, urgency (compelling need to void that cannot be
deferred), urgency incontinence, and voiding at night (nocturia). >rinary incontinence may occur, and
nocturia may contribute to insomnia.
9oiding symptoms include urinary hesitancy (difficulty initiating the stream), straining to void, "ea' or
intermittent stream (starts and stops), and incomplete bladder emptying. Pain and dysuria are
usually not present. #hese storage and voiding symptoms are evaluated using the ?nternational
Prostate 4ymptom 4core (?P44) &uestionnaire, designed to assess the severity of BPH. [-
BPH can be a progressive disease, especially if left untreated. ?ncomplete voiding results in stasis of
bacteria in the bladder residue and an increased ris' of urinary tract infection. >rinary bladder
stones are formed from the crystallization of salts in the residual urine. >rinary retention,
termed acute or chronic, is another form of progression. cute urinary retention is the inability to
void, "hile in chronic urinary retention the residual urinary volume gradually increases, and the
bladder distends. #his can result in bladder hypotonia. 4ome patients "ho suffer from chronic
urinary retention may eventually progress to renal failure, a condition termedobstructive uropathy.
Causes[edit
7ost e+perts consider androgens (testosterone and related hormones) to play a permissive role.
#his means that androgens have to be present for BPH to occur, but do not necessarily directly
cause the condition. #his is supported by the fact that castrated boys do not develop BPH "hen they
age. @n the other hand, administering e+ogenous testosterone is not associated "ith a significant
increase in the ris' of BPH symptoms.[citation needed 6ihydrotestosterone (6H#), a metaboliteof
testosterone, is a critical mediator of prostatic gro"th. 6H# is synthesized in the prostate from
circulating testosterone by the action of the enzyme -Areductase, type . #his enzyme is localized
principally in the stromal cells hence, those cells are the main site for the synthesis of 6H#.
6H# can act in an autocrine fashion on the stromal cells or in paracrine fashion by diffusing into
nearby epithelial cells. ?n both of these cell types, 6H# binds to nuclear androgen receptors and
signals the transcription of gro"th factors that are mitogenic to the epithelial and stromal cells. 6H#
is 1 times more potent than testosterone because it dissociates from the androgen receptor more
slo"ly. #he importance of 6H# in causing nodular hyperplasia is supported by clinical observations
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in "hich an inhibitor of -Areductase such as finasteride is given to men "ith this condition. #herapy
"ith a -Areductase inhibitor mar'edly reduces the 6H# content of the prostate and, in turn, reduces
prostate volume and, in many cases, BPH symptoms. [citation needed
#estosterone promotes prostate cell proliferation,[: but relatively lo" levels of serum testosterone are
found in patients "ith BPH. [/[0 @ne small study has sho"n that medical castration lo"ers the serum
and prostate hormone levels unevenly, having less effect on testosterone and dihydrotestosterone
levels in the prostate. [=
!hile there is some evidence that estrogen may play a role in the etiology of BPH, this effect
appears to be mediated mainly through local conversion of androgens to estrogen in the prostate
tissue rather than a direct effect of estrogen itself. [1 ?n canine in vivo studies castration, "hich
significantly reduced androgen levels but left estrogen levels unchanged, caused significant atrophy
of the prostate.[11 4tudies loo'ing for a correlation bet"een prostatic hyperplasia and serum estrogen
levels in humans have generally sho"n none.[0[1
?n 0, Cigal Dat et al. published evidence that BPH is caused by failure in the spermatic venous
drainage system resulting in increased hydrostatic pressure and local testosterone levels elevated
more than 1 fold above serum levels.[1* ?f confirmed, this mechanism e+plains "hy serum
androgen levels do not seem to correlate "ith BPH and "hy giving e+ogenous testosterone "ould
not ma'e much difference. #his also has implications for treatment (see 7inimally invasive therapies
belo").
@n a microscopic level, BPH can be seen in the vast maEority of men as they age, in particular over
the age of / years, around the "orld. Ho"ever, rates of clinically significant, symptomatic BPH vary
dramatically depending on lifestyle. 7en "ho lead a "estern lifestyle (need definition of $"estern lifestyle$) have a much
higher incidence of symptomatic BPH than men "ho lead a traditional or rural lifestyle(Feed definition of $rural
lifestyle$). #his is supported by research [citation needed in 5hina sho"ing that men in rural areas have very lo"
rates of clinical BPH, "hile men living in cities adopting a "estern lifestyle have a s'yroc'eting
incidence of this condition, though it is still belo" rates seen in the !est. ?t also seems [citation needed that
there is some connection bet"een microcalcifications bet"een prostate cancer and BPH, as is
demonstrated in -/- of men over - years.[clarification needed
Pathophysiology [edit
Both the glandular epithelial cells and the stromal cells (including muscular fibers) undergo
hyperplasia in BPH.[12G:=2 7ost sources agree that of the t"o tissues, stromal hyperplasia
predominates, but the e+act ratio of the t"o is unclear .[12G:=2
natomically, BPH is most strongly associated "ith the posterior urethral glands (P>D) and
transitional zone (#) of the prostate. #he earliest microscopic signs of BPH usually begin bet"een
the age of * and - years old in the P>D, "hich are posterior to the pro+imal urethra. [12G:=2 ?n BPH,
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the maEority of gro"th occurs in the #. [12G:=2 ?n addition to these t"o classic areas, the peripheral
zone (P) of the prostate is also involved to a lesser e+tent. [12G:=- Prostatic cancer typically occurs in
the P. Ho"ever, BPH nodules, usually from the # are often biopsied any"ay to rule out cancer in
the #.[12G:=- Ho"ever, cancers of the prostate most fre&uently occur in the P rather than the #,
thus, chippings ta'en from the P are of limited use.
Diagnosis[edit
7icrograph sho"ing nodular hyperplasia (left off center) of the prostate from a transurethral resection of the
prostate (#>%P). HI; stain.
7icroscopic e+amination of different types of prostate tissues (stained "ithimmunohistochemical techni&ues)G .
Formal (nonneoplastic) prostatic tissue (FF#). B. Benign prostatic hyperplasia. 5. Highgrade prostatic intraepithelial
neoplasia (P?F). 6.Prostatic adenocarcinoma (P5).
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Prostate "ith a large median lobe bulging up"ards. metal instrument is placed in the urethra ("hich passes through
the prostate). #his specimen "as almost / centimeters long "ith a volume of about : cubic centimetres
on transrectal ultrasound and "as removed during a Hryntscha' procedure or transvesicalprostatectomy (removal of
the prostate through the bladder) for benign prostatic hyperplasia.
%ectal e+amination (palpation of the prostate through the rectum) may reveal a mar'edly enlarged
prostate, usually affecting the middle lobe.
@ften, blood tests are performed to rule out prostatic malignancyG elevated prostate specific
antigen (P4) levels needs further investigations such as reinterpretation of P4 results, in terms of
P4 density and P4 free percentage, rectal e+amination and transrectal ultrasonography. #hese
combined measures can provide early detection.
>ltrasound e+amination of the testicles, prostate, and 'idneys is often performed, again to rule
out malignancy andhydronephrosis.
4creening and diagnostic procedures for BPH are similar to those used for prostate cancer . 4ome
signs to loo' for includeG [1-
•
!ea' urinary stream• Prolonged emptying of the bladder
• bdominal straining
• Hesitancy
• ?rregular need to urinate
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• ?ncomplete bladder emptying
• Posturination dribble
• ?rritation during urination
• <re&uent urination
• Focturia (need to urinate during the night)
• >rgency
• ?ncontinence (involuntary lea'age of urine)
• Bladder pain
• 6ysuria (painful urination)
• Problems in eEaculation
Management[edit
Lifestyle[edit
8ifestyle alterations to address the symptoms of BPH include decreasing fluid inta'e before bedtime,
moderating the consumption of alcohol and caffeinecontaining products, and follo"ing a timed
voiding schedule. Patients can also attempt to avoid products and medications that may e+acerbate
symptoms of BPH, including antihistamines, diuretics, anddecongestants, opiates, and tricyclic
antidepressants, ho"ever this should be done "ith input from a medical professional. [1:
Voiding position[edit
nother influencing factor is the position in "hich patients are used to urinating, for e+ample sitting
do"n "hile urinating[1/ ametaanalysis [10 found that, for elderly males "ith lo"er urinary tract
symptoms (8>#4)G
• the post void residual volume (P9%, ml) "as significantly decreased
• the ma+imum urinary flo" (Jma+, mlKs) "as increased, comparable "ith pharmacological
intervention
• the voiding time (9#, s) "as decreased
#his urodynamic profile is related to a lo"er ris' of urologic complications, such
as cystitis and bladder stones.
Medications[edit
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#he t"o main medications for management of BPH are alpha bloc'ers and -Areductase inhibitors.
lpha bloc'ers (technically A1adrenergic receptor antagonists) are the most common choice for
initial therapy in the >4[1=[ and ;urope.[1 lpha bloc'ers used for BPH include do+azosin,
[ terazosin, alfuzosin,[*[2 tamsulosin, andsilodosin. ll five are e&ually effective but have slightly
different side effect profiles. [- #he older drugs pheno+ybenzamineand prazosin are not
recommended.[: lpha bloc'ers rela+ smooth muscle in the prostate and the bladder nec', thus
decreasing the bloc'age of urine flo". 5ommon side effects of alpha bloc'ers include orthostatic
hypotension, (a head rush or dizzy spell "hen standing up or stretching), eEaculation changes,
headaches, nasal congestion, and "ea'ness. Fonselective alpha bloc'ers such
as terazosin and do+azosin may also re&uire titration as they can cause syncope if the dose is too
high. 4ide effects can also include erectile dysfunction. [/
#he -Areductase inhibitors finasteride [0 and dutasteride [= are another treatment option. #hese
medications inhibit -areductase, "hich in turn inhibits production of 6H#, a hormone responsible for
enlarging the prostate. ;ffects may ta'e longer to appear than alpha bloc'ers, but they persist for
many years.[* !hen used together "ith alpha bloc'ers, a reduction of BPH progression to acute
urinary retention and surgery has been noted in patients "ith larger prostates. [*1 4ide effects include
decreased libido and eEaculatory or erectile dysfunction. [0
ntimuscarinics such as tolterodine may also be used, especially in combination "ith alpha bloc'ers.
[* #hey act by decreasing acetylcholine effects on the smooth muscle of the bladder , thus helping
control symptoms of an overactive bladder .[citation needed
?n 11, the >.4. <ood and 6rug dministration approved 5ialis (tadalafil) to treat the signs and
symptoms of benign prostatic hyperplasia (BPH), and for the treatment of BPH and erectile
dysfunction (;6), "hen the conditions occur simultaneously.[** 5ialis "as approved in * for the
treatment of ;6.[*2
4ildenafil citrate sho"s some symptomatic relief, suggesting a possible common etiology
"ith erectile dysfunction.[*- #adalafil "as considered then reEected by F?5; in the >L for the
treatment of symptoms associated "ith BPH. [*:
Minimally invasive therapies[edit
#he ;uropean >rology %evie"[*/ published in = that t"o ?sraeli doctors, Cigal Dat and 7enahem
Doren, have developed the DatDoren nonsurgical method for BPH.[*0 >sing an interventional
radiological techni&ue that reduces prostate volume and reverses BPH symptoms, the treatment,
'no"n as superselective intraprostatic androgen deprivation (4P6) therapy, involves
a percutaneous venography and sclerotherapy of the internal spermatic vein net"or', including
associated venous bypasses and retroperitoneal collaterals. #he ;uropean >rology %evie" also
declared that using the Dat Doren nonsurgical method results in decreased prostate volume, "hich
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leads to significantly decreased nocturia, improved urine stream, and also improves emptying of the
urinary bladder, and that "ithout the potential side effects and complications of the classic surgery.
lthough medication is often prescribed as the first treatment option, there are many patients "ho do
not achieve success "ith this line of treatment. #hose patients may not achieve sustained
improvement in symptoms or they may stop ta'ing the medication because of sideeffects.[*= #here
are options for treatment in a urologistMs office before proceeding to surgery. #he t"o most common
types of officebased therapies are transurethral micro"ave thermotherapy (#>7#) andtransurethral
needle ablation (#>F). Both of these procedures rely on delivering enough energy to create
sufficient heat to cause cell death (necrosis) in the prostate. #he goal of the therapies is to cause
enough necrosis so that, "hen the dead tissue is reabsorbed by the body, the prostate shrin's,
relieving the obstruction of the urethra. #hese procedures are typically performed "ith local
anesthesia, and the patient returns home the same day. 4ome urologists have studied and
published longterm data on the outcomes of these procedures, "ith data out to five years. #he most
recent merican >rological ssociation (>) Duidelines for the #reatment of BPH in * lists
minimally invasive therapies including #>7# and #>F as acceptable alternatives for certain
patients "ith BPH.[2
#ransurethral micro"ave therapy (#>7#) "as originally approved by the >nited 4tates <ood and
6rug dministration (<6) in 1==:, "ith the first generation system by ;6P #echnomed. 4ince
1==:, other companies have received <6 approval for #>7# devices, including >rologi+, 6ornier,
#hermatri+, 5elsion, and Prostalund. 7ultiple clinical studies have been published on #>7#. #he
general principle underlying all the devices is that a micro"ave antenna that resides in a urethral
catheter is placed in the intraprostatic area of the urethra. #he catheter is connected to a control bo+
outside of the patientMs body and is energized to emit micro"ave radiation into the prostate to heat
the tissue and cause necrosis. ?t is a onetime treatment that ta'es appro+imately * minutes to 1
hour, depending on the system used. ?t ta'es appro+imately 2 to : "ee's for the damaged tissue to
be reabsorbed into the patientMs body. 4ome of the devices incorporate circulating coolant through
the treatment area "ith the intent of preserving the urethra "hile the micro"ave energy heats the
prostatic tissue surrounding the urethra.
#ransurethral needle ablation (#>F) operates "ith a different type of energy, radio fre&uency (%<)
energy, but is designed along the same premise as #>7# devices, that the heat the device
generates "ill cause necrosis of the prostatic tissue and shrin' the prostate. #he #>F device is
inserted into the urethra using a rigid scope much li'e a cystoscope. #he energy is delivered into the
prostate using t"o needles that emerge from the sides of the device, through the urethral "all and
into the prostate. #he needlebased ablation devices are very effective at heating a localized area to
a high enough temperature to cause necrosis. #he treatment is typically performed in one session,
but may re&uire multiple stic's of the needles depending on the size of the prostate.
Surgery[edit
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?f medical treatment fails, and the patient elects not to try officebased therapies or the physician
determines the patient is a better candidate for transurethral resection of prostate (#>%P), surgery
may need to be performed. ?n general, #>%P is still considered the gold standard of prostate
interventions for patients "ho re&uire a procedure. #his involves removing (part of) the prostate
through the urethra. Ho"ever after this endscopic surgery the eEaculations are dry and the personbecomes sterile. <or a male "ho "ishes to father a child this is not the procedure of choice. @ver the
past couple of decades efforts to find ne"er surgical methods have resulted in ne"er approaches
and different types of energies being used to treat the enlarged gland. Ho"ever some of the ne"er
methods for reducing the size of an enlarged prostate, have not been around long enough to fully
establish their safety or sideeffects. #hese include various methods to destroy or remove part of the
e+cess tissue "hile trying to avoid damaging "hat remains. #ransurethral electrovaporization of the
prostate (#9P), laser #>%P, visual laser ablation (98P), ethanol inEection, and others are studied as
alternatives.
Fe"er techni&ues involving lasers in urology have emerged in the last -31 years, starting "ith the
98P techni&ue involving the FdGCD laser "ith contact on the prostatic tissue. similar technology
called Photoselective 9aporization of the Prostate (P9P) "ith the Dreen8ight (L#P or 8B@ crystal)
laser have emerged very recently. #his procedure involves a highpo"er 10"att -* nm
"avelength laser "ith a :-micrometre laser fiber inserted into the prostate. #his fiber has an
internal reflection "ith a /degree deflecting angle. ?t is used to vaporize the tissue to the prostatic
capsule. Dreen8ight -* nm lasers target haemoglobin as thechromophore and typically have a
penetration depth of .0mm (t"o times deeper than holmium).
nother procedure termed Holmium 8aser blation of the Prostate (Ho8P) has also been gaining
acceptance around the "orld. 8i'e L#P, the delivery device for Ho8P procedures is a -- um
disposable sidefiring fiber that directs the beam from a highpo"er 1"att laser at a /degree
angle from the fiber a+is. #he holmium "avelength is ,12 nm, "hich falls "ithin the infrared portion
of the spectrum and is invisible to the na'ed eye. !hereas Dreen8ight relies on haemoglobin as a
chromophore, "ater "ithin the target tissue is the chromophore for Holmium lasers. #he penetration
depth of Holmium lasers is N.2 mm, avoiding complications associated "ith tissue necrosis often
found "ith the deeper penetration and lo"er pea' po"ers of FdGCD lasers used in the 1==s.
Ho8;P, Holmium 8aser ;nucleation of the Prostate, is another Holmium laser procedure reported to
carry fe"er ris's compared "ith either #>%P or open prostatectomy.[21 Ho8;P is largely similar to
the Ho8P procedure the main difference is that this procedure is typically performed on larger
prostates. ?nstead of ablating the tissue, the laser cuts a portion of the prostate, "hich is then cut
into smaller pieces and flushed "ith irrigation fluid. s "ith the Ho8P procedure, there is little
bleeding during or after the procedure.
Both "avelengths, Dreen8ight and Holmium, ablate appro+imately one to t"o grams of tissue per
minute.
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Post surgery care often involves placement of a <oley catheter or a temporary prostatic stent to
permit healing and allo" urine to drain from the bladder.
?n summary, the surgical techni&ues used areG
• @pen prostatectomyG not usually performed no"adays, even if results are very good.
• #ransurethral resection of the prostate (#>%P)G the gold standard.
• #ransurethral incision of the prostate (#>?P)G rarely performed the techni&ue is similar to
#>%P but less definitive.
• 8aser vaporization of the prostateG common treatment.
• #ransurethral micro"ave therapy (#>7#)G similar to laser ablation, but less effective and
much less used.
• #ransurethral needle ablation (#>F)G not very effective.
• Holmium laser enucleation of the prostate (Ho8;P)G more and more used, it "ill probably
replace #>%P in the future.
Alternative medicine[edit
Herbal remedies are a commonly sought treatment for BPH, [2 and several are approved in
;uropean countries, and available in the >4. 4a" palmetto e+tract fromSerenoa repens is one of
the most commonly used and studied, having sho"ed some promise in early studies. [2* 8ater trials of
higher methodological &uality have sho"n it to be no better than placebo in both symptom relief and
decreasing prostate size.[22[2-[2:
@ther herbal medicines include betasitosterol [2/ from Hypoxis rooperi (frican star grass)
and pygeum (e+tracted from the bar' of Prunus africana),[20 "hile there is less substantial support for
the efficacy of pump'in seed (Cucurbita pepo) and stinging nettle (Urtica dioica) root.[2=
Epidemiology [edit
6isabilityadEusted life year for benign prostatic hyperplasia per 1, inhabitants in 2.[-
no data
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less than
30
03*:
*:322
223-
-3:
:3:0
:03/:
/:302
023=
=31
more than 1
Dlobally, benign prostatic hyperplasia affects about 1 million males as of 1 (: of the
population).[-1#he prostate gets larger in most men as they get older. <or a symptomfree man of 2:
years, the ris' of developing BPH over the ne+t * years is 2-. ?ncidence rates increase from *
cases per 1 manyears at age 2-32= years, to *0 cases per 1 manyears by the age of /-3
/= years. !hile the prevalence rate is ./ for men aged 2-32=, it increases to 2 by the age of
0 years.[-