P

Received: January 31, 2007 Accepted: February 28, 2007

Address correspondence to: Dr. Hann-Chorng Kuo, Department of Urology, Buddhist
Tzu Chi General Hospital, 707, Section 3, Chung Yang Road, Hualien, Taiwan
E-mail: hck@tzuchi.com.tw
Differential Diagnosis of Male Lower Urinary Tract Symptoms
Suggestive of Benign Prostatic Hyperplasia and Non-Benign
Prostatic Hyperplasia
Hann-Chorng Kuo, M.D.
Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan
Incont Pelvic Floor Dysfunct 2007; 1 (Suppl 1):3-6
INTRODUCTION
Lower ur|nary rac sympoms (LUTS) |nc|uoe sorae sympoms
(|ncreaseo b|aooer sensa|on, requency, urency, ure |ncon|nence
ano nocur|a), empy|n sympoms (hes|ancy, oysur|a, |nerm|ency,
s|ow sream, erm|na| or|bb|e ano res|oua| ur|ne sensa|on) ano pa|n
sympoms (pe|v|c pa|n, per|nea| pa|n ano urehra| pa|n). LUTS are h|h|y
preva|en |n men ano women, ano |ncrease w|h ae [1|. LUTS are
common amon e|oer|y men ano are hereore usua||y cons|oereo syn-
onymous w|h ben|n prosa|c hyperp|as|a (BPH). However, | as been
es|maeo ha on|y 25% o 50% o men w|h BPH have LUTS ano on|y
50% o men w|h LUTS have urooynam|ca||y proven b|aooer ou|e ob-
sruc|on (BOO) oue o BPH or oher urehra| cono||ons [2|.
PREVALENCE OF MALE LUTS
The preva|ence ano sever|y o LUTS |ncreases w|h ae, ano he
proress|ve |ncrease |n he ae|n popu|a|on has |ncreaseo he so-
c|a| econom|c buroen ano sever|y o LUTS [3|. Amon LUTS, preva-
|ence ha |ncreases w|h ae |s ouno on|y or urency, weak sream
ano nocur|a, he oher sympoms are equa||y o|sr|bueo amon ae
roups [4|. A|houh he preva|ence raes o nocur|a, requency, ure
|ncon|nence ano nocurna| |ncon|nence are re|a|ve|y |ow, he boher-
someness o hese sympoms |s very h|h [5|. n an ep|oem|o|o|ca|
suoy |n easern Ta|wan, nocur|a (>2 vo|os per n|h) was he mos
bohersome LUTS |n abor||nes ano non-abor||nes, w|h a preva|ence
rae o 31.1% ano 19.8%, respec|ve|y. Abou 15% o men reporeo
he|r LUTS have a rea |mpac on he|r qua||y o ||e [6|.
PATHOPHYSIOLOGY OF MALE LUTS
The pahophys|o|oy o LUTS cou|o be b|aooer oysunc|on
(b|aooer hypersens||v|y, oerusor overac|v|y (DO)), BOO (b|aooer
neck oysunc|on, prosa|c obsruc|on, urehra| sr|cure, poor|y re-
|axeo urehra| sph|ncer, urehra| sph|ncer oyssyner|a) or a comb|-
na|on o hese e|o|o|es [7|. Many men have boh sorae ano empy-
|n sympoms. n men, empy|n sympoms are more common bu
sorae sympoms are a|so encounereo requen|y [8|. Frequen
comorb|o|y w|h prosa|c o|seases aoos o he comp|ex|y o o|ano-
s|s ano manaemen o ma|e LUTS.
ASSESSMENT OF MALE LUTS
Assessmen o ma|e LUTS |nc|uoes a se|-assesseo sympom
score ques|onna|re such as he Amer|can Uro|o|ca| Assoc|a|on (AUA)
sympom score ano nerna|ona| Prosae Sympom Score (PSS) [9|.
A vo|o|n o|ary recoro|n he requency o urency ep|sooes ano he
vo|oeo vo|ume prov|oes rea he|p |n he |n||a| o|anos|s o overac|ve
b|aooer (OAB) or po|yur|a cono||ons. Uro|omery ano posvo|o re-
s|oua| ur|ne (PVP), prosa|c measuremen us|n o||a| reca| exam|-
na|on (DPE), ransreca| or ransaboom|na| sonoraphy are ava||ab|e
c||n|ca| |nves|a|ons or assessmen o uro|ow ano b|aooer ou|e
cono||on. n oroer o assess he |ower ur|nary rac neurophys|o|oy, a
neuro|o|ca| exam|na|on |s necessary, such as bu|bocavernosus re|ex,
per|nea| sensa|on ano sponaneous ana| sph|ncer conrac|on.
Cysomery, urehra| sph|ncer e|ecromyoraphy (EMG) ano pressure
|ow suoy w|h or w|hou c|ne|uoroscopy can prov|oe urher |norma-
|on o oerusor unc|on ano sph|ncer ac|v|y. Cysoscopy can a|so
he|p us |n he o|anos|s o urehra| sr|cure or severe prosa|c
obsruc|on. Aer he |n||a| o|anos|s, ma|e pa|ens w|h LUTS can be
c|ass||eo |no LUTS sues|ve o BPH, LUTS sues|ve o DO, oe-
rusor unoerac|v|y or o neuro|o|ca| or||n. Pa|ens m|h have a
comb|na|on o oerusor oysunc|on ano BOO or urehra| cono||ons.
LUTS IN BOO
BOO |s a urooynam|c cono||on |mp|y|n vo|o|n w|h a h|h pres-
sure ano/or |ow |ow rae. Pa|ens w||| oeve|op LUTS (sorae ano/or
empy|n LUTS) when BOO has oeve|opeo o a cons|oerab|e oeree.
BOO can occur |n men ano women, |n aou|s ano ch||oren, ano |n
anaom|ca| ano neuroen|c cono||ons. n a suoy |nves|a|n men
w|hou BOO ano LUTS, he max|mum |ow rae (Qmax) reacheo up o
20 mL/s w|h a mean vo|oeo vo|ume o 290 mL (Tab|e 1). One h|ro o
men w|h LUTS oo no have BOO. Many c||n|ca| suo|es have oemon-
sraeo ha LUTS have a poor o|anos|c spec||c|y or BOO ano 5%-
35% o pa|ens w|h BPH ano LUTS oo no have |mproveo sympoms
aer ransurehra| resec|on o he prosae (TUPP) [10|. The prosae
s|ze ano uro|owmery have beer corre|a|on w|h a urooynam|c suoy
han sympoms a|one.
C||n|ca| BPH |s oe|neo as hav|n a |eas wo o he o||ow|n: (1)
mooerae o severe LUTS (PSS 8), (2) an en|areo prosae (oa|
prosa|c vo|ume (TPV) 30 mL) ano (3) oecreaseo Qmax (<15 mL/s)
Q
H. C. Kuo
[11|. A|houh an en|areo prosae m|h no |no|cae he presence o
BOO, he mean TPV o pa|ens w|h BOO |s s|n||can|y h|her han
ha o pa|ens w|hou BOO [12|. n aoo||on, pa|ens w|h LUTS su-
es|ve o BPH ano w|h a Qmax o <10 mL/s have a reaer |mprove-
men |n Qmax aer TUPP compareo w|h hose w|h a Qmax o >10
mL/s. Pa|ens w|hou ev|oence o BOO preopera|ve|y a|so have a
poor pronos|s aer TUPP [13|. Pa|ens w|h posopera|ve LUTS are
ouno o have a sma|| TPV a he |me o surery, sues|n ha a
non-BPH e|o|oy m|h accoun or he|r LUTS [14|. Thereore, o|a-
nos|s o c||n|ca| BPH shou|o be careu||y unoeraken, espec|a||y when
an |nvas|ve proceoure such as TUPP |s o|n o be perormeo. The
o|eren|a| o|anos|s or non-BPH LUTS |s ||seo |n Tab|e 2.
LUTS IN NON-BPH CONDITIONS
Bladder hypersensitivity
Amon he var|ous e|o|o|es o LUTS oue o non-BPH cono||ons,
b|aooer hypersens||v|y ano DO are common|y ouno, espec|a||y |n
e|oer|y men. Sensory urency may be he presen|n sympom o pa-
|ens w|h DO, poor re|axa|on o urehra| sph|ncer, |ners||a| cys||s,
BOO or neuroen|c vo|o|n oysunc|on. Pecen |nves|a|on has
shown ha he urohe||a| re|ease o neuroransm|ers, such as acey|-
cho||ne (Ach), aoenos|ne r|phosphae (ATP) ano he neuropep|oe
subsance P, ano he express|on o TPPV1 ano P2X3 recepors sron|y
|mp|y a ro|e or he urohe||um |n human b|aooer mechanosensa|on
[15,16|. The re|ease o urohe||a| Ach oecreases bu ATP proouc|on
|ncreases w|h ae|n. These phys|o|o|ca| chanes |no|cae he h|h
preva|ence rae o b|aooer hypersens||v|y ano OAB, ano are poss|b|y
respons|b|e or he occurrence o oerusor hyperac|v|y ano |mpa|reo
conrac|||y (DHC) |n e|oer|y men [17|.
Polyuria
A number o pa|ens may have |are oa||y ur|ne oupu o over
2800 mL/oay. Pa|ens may have po|yo|ps|a ano h|h waer |nake,
ano hereore may have requency w|h vo|oeo vo|ume >350 mL ye
are ||ke|y o be phys|o|o|ca||y norma| [18|. However, or hese pa|ens,
we shou|o check he|r meabo||c saus, |nc|uo|n o|abees, azoem|a,
hyper||p|oem|a, o|ure|c meo|ca|ons ano s|eep apnea synorome.
Psychological factors
Anoher cono||on |s psycho|o|ca|, soc|a| or psych|ar|c acors
ha m|h cause requency |n ma|e pa|ens. These pa|ens may have
a h|h |eve| o o|sress ano a h|h |eve| o anx|ey. The sympoms may
worsen |n re|a|on o work or sress. They may a|so be||eve here |s a
re|a|onsh|p beween he|r sympoms ano o|seases such as urem|a,
|nec|on or cancer.
Urothelial dysfunction
Sensory urency m|h be m|cro-moor urency oue o m|cro-
mo|on o he oerusor our|n rap|o b|aooer ||||n, such as |n o|ures|s.
Pa|ens may have severe urency when he|r b|aooer vo|ume |s sma||
ano h|s cono||on m|h be he cause o urohe||a| oysunc|on, such
as |n r|ona| mucosa oysunc|on. The r|one |s abunoan |n sensory
nerves ano subr|one oenerva|on has been useo o rea OAB |n
women [19|. ncreaseo TPPV1 recepor express|on has been ouno |n
sensory urency bu no |n |o|opah|c oerusor overac|v|y (DO), ano
r|ona| ano b|aooer base |njec|on o bou||num ox|n A (BTX-A) |s
eec|ve |n pa|ens w|h severe urency requency synorome rerac-
ory o conserva|ve meo|ca| reamen ano e|ecr|ca| s|mu|a|on [20|.
Pa|ens w|h pseuoomembranous r|on||s usua||y suer rom severe
urency ha |s reracory o an|muscar|n|cs. Unoer h|s cono||on, |n-
raves|ca| res|n|eraox|n |ns|||a|on or subr|ona| BTX-A |njec|on m|h
reouce sensory urency |n pa|ens w|h OAB ory. ncreaseo nerve
rowh acor (GF) |eve|s have been ouno |n b|aooer b|ops|es w|h
sensory urency, chron|c cys||s ano |ners||a| cys||s compareo o
|eve|s |n conro|s [21|. mmunosa|n|n has shown |ncreaseo GF ex-
press|on |n he urohe||um, mos markeo |n |o|opah|c sensory urency,
hereore an|-GF reamen may be appropr|ae |n pa|ens w|h sen-
sory urency. nraves|ca| BTX-A has been ouno o oecrease symp-
oms o DO ano c|ean |nerm|en caheer|za|on (CC), ano he pro-
ouc|on o GF has been ouno o reouce aer BTX-A reamen |n
pa|ens w|h neuroen|c oerusor overac|v|y (DO), DO or CC
(unpub||sheo oaa).
Overactive bladder
Pecen |nves|a|ons o ma|e LUTS noeo ha b|aooer oysunc-
|on p|ays an |mporan ro|e |n aoo||on o BOO. LUTS sues|ve o
OAB have been es|maeo o be presen |n 16% o peop|e |n Europe
ano he Un|eo Saes [1|. A mu||na|ona| |are sca|e suoy revea|eo
Table 1. Normal Uroflow rate in Taiwanese Men by Age
Age years Qmax (mL/S) Voided volume (mL) CQmax
45 23.98.73 (127) 339.8191.1 1.410.51
46-55 19.76.81 ( 68) 305.4159.2 1.210.42
56-65 20.26.20 (134) 286.8138.8 1.270.42
66-75 19.26.10 (143) 262.8109.3 1.230.39
76-85 18.77.50 ( 42) 225.3101.5 1.310.47
All ages 20.77.30 (514) 290.7123.2 (514) 1.290.45 (514)
Table 2. Differential Diagnosis of Male LUTS/BOO & Non-BOO
Badder neck dysfunction
Bladder hypersensitivity
Overactive bladder
Spastic urethral sphincter
Poor relaxation of urethral sphincter
Urethral stricture
Low detrusor contractility
Pseudodyssynergia due to neuropathy
R
ha 90% o men aeo 50 o 80 years suer rom poen|a||y roub|e-
some LUTS, ano many men have boh sorae ano vo|o|n sympoms
[22|. OAB sympoms compr|se he same sympoms as sorae LUTS
|n BPH ano he|r preva|ence |ncreases w|h ae. S|nce mos men w|h
OAB oo no exper|ence |ncon|nence, men w|h sorae LUTS are o-
en m|so|anoseo w|h c||n|ca| BPH [23|. However, sorae LUTS cor-
re|ae poor|y w|h BOO as ma|e OAB sympoms may be causeo by
b|aooer oysunc|on such as DO or DHC, or occur |n comb|na|on w|h
BOO [7|. However, many suo|es have reporeo on|y 45%-50% o men
w|h LUTS have urooynam|ca||y con|rmeo DO ano BOO [2,24|.
DO can be oue o |o|opah|c myoen|c overac|v|y, poor cor|ca|
perus|on, pos-obsruc|ve DO, he ae|n process or DHC. n men
w|h LUTS, we shou|o exc|uoe BOO |rs. n a recen suoy o he paho-
phys|o|oy o ma|e LUTS, on|y 29.4% o men hao ben|n prosa|c
obsruc|on (BPO) ano 51.1% o ma|e LUTS was oue o DO (unpub||sheo
oaa). Amon he pa|ens w|h BPO, 80.9% o men hao DO. However,
amon he pa|ens w|h urooynam|c DO, on|y 48% o men hao
urooynam|c BPO. Pa|ens w|h BPO bu w|hou OAB sympoms m|h
oeve|op oe novo OAB aer TUPP, sues|n ha oesruc|on o he
r|one mucosa m|h |eao o OAB [25|. Treamen o pa|ens w|h
BPO ano OAB shou|o |nc|uoe aens ha re||eve urehra| res|sance
as we|| as an|muscar|n|cs when he OAB sympoms canno be re-
so|veo by rea|n w|h an a|pha-b|ocker or comb|neo 5 a|pha-reouc-
ase |nh|b|or.
Nocturia and nocturnal polyuria
LUTS are common |n he e|oer|y ano nocur|a |s he h|ro mos
bohersome LUTS. The preva|ence o nocur|a |ncreases o 80% |n
pa|ens aeo over 80 years. ocur|a |s one o he mos common causes
o o|surbeo s|eep paerns |n he e|oer|y. The causes o nocur|a |n-
c|uoe DO, hypersens||ve b|aooer, BOO, nocurna| po|yur|a or sma||
b|aooer capac|y. When he nocurna| ur|ne vo|ume >900 mL or more
han 35% o he oa||y vo|oeo vo|ume, nocurna| po|yur|a |s ||ke|y. Lack
o o|urna| oesmopress|n rhyhm can cause nocurna| po|yur|a ano can
be reaeo w|h exoenous oesmopress|n such as DDAVP [26|. n
aoo||on, or pa|ens w|h comb|neo nocurna| po|yur|a ano BOO or
OAB, comb|neo mu||p|e meo|ca|on |s necessary o re||eve he com-
p|ex ma|e LUTS.
Poor relaxation of the urethral sphincter
Amon he var|ous causes o non-BOO ma|e LUTS, poor re|axa-
|on o he urehra| sph|ncer |s he mos requen|y encounereo cono|-
|on [27|. Pa|ens m|h have sympoms o hes|ancy, |nerm|ency,
s|ow sream or posvo|o or|bb|e. Some pa|ens m|h a|so have sor-
ae sympoms such as urency or requency. The causes o poor re-
|axa|on o he urehra| sph|ncer m|h be |earneo hab|, chron|c
prosa||s, pe|v|c |oor hyperon|c|y, occu| neuropahy or |ncreaseo
b|aooer sens||v|y. A|houh h|s cono||on ooes no aec ur|nary rac
unc|on, he sympoms m|h have a rea |mpac on he qua||y o ||e,
espec|a||y |n a youn popu|a|on. D|anos|s can be maoe by
uro|owmery, comb|neo EMG suoy or v|oeourooynam|c pressure |ow
suoy.
Pain symptoms
Severa| cono||ons can cause pa|n sympoms |n men. ners||a|
cys||s, BOO, poor comp||an b|aooer ano rans||ona| ce|| carc|noma
can cause a pa|nu| b|aooer. Ur|nary rac |nec|on, urehra| sr|cure,
BPO ano chron|c prosa||s can cause a pa|nu| urehra. A pa|nu| pe|-
v|s or pa|nu| per|neum can be oue o pe|v|c |oor hyperon|c|y, chron|c
prosa||s, spas|c urehra| sph|ncer or per|ana| |n|amma|on. Trea-
men o pa|n sympoms |n men |s no easy ano shou|o be baseo on he
exac o|anos|s o he pa|n sympoms. D||a| reca| exam|na|on (DPE)
ano prosa| c massae or exam| na| on o prosa| c | u| o,
urehrocysoscopy o exc|uoe urehra| sr|cure, or perorm|n ranoom
b|aooer b|ops|es o |nves|ae he poss|b|||y o carc|noma |n s|u are
o|anos|c proceoures necessary or pa|n sympoms |n men.
Trans||ona| ce|| carc|noma o he b|aooer usua||y m|m|cs |ners|-
|a| cys||s |n men w|h LUTS ano pa|nu| b|aooer synorome. Charac-
er|s|c |omeru|a|on may appear aer cysoscop|c hyoroo|sen|on
ano b|aooer b|opsy revea|s nonspec||c chron|c cys||s. However, when
|on-erm meo|ca|ons such as penosan po|ysu|phae or COX-2 |n-
h|b|or a|| o re||eve he sympoms, repea cysoscopy, ur|ne cyo|oy
ano repea ranoom b|aooer b|opsy are necessary |n oroer o oeec
ear|y b|aooer carc|noma.
Post-prostatectomy male LUTS
Over ha| o he pa|ens w|h pos-prosaecomy LUTS have a
sma|| oa| prosae vo|ume ano reseceo aoenoma we|h, |no|ca|n
he|r LUTS were non-BPH or non-BOO cono||ons beore TUPP. Amon
pa|ens w|h pos-prosaecomy LUTS, norma| urehra ano b|aooer
are noeo |n 9.1%, DO |n 9.6%, oerusor unoerac|v|y |n 18.7%, poor
re|axeo exerna| sph|ncer |n 19.3%, DHC |n 14.4% ano res|oua| BOO
|n 27.8% [14|. Dea||eo cysoscopy ano v|oeourooynam|c suoy are
necessary or hese pa|ens, espec|a||y when hey are o|anoseo o
have res|oua| BPH or BOO ano are o unoero repea ransurehra|
surery. A narrow urehra| semen m|h no necessar||y be respon-
s|b|e or he pos-prosaecomy LUTS. DHC, b|aooer hypersens||v|y
or OAB can a|so be causes o ma|e LUTS |n he presence o a sma||
BPH.
Other conditions
Urehra| sph|ncer pseuoooyssyner|a |n pa|ens w|h chron|c
sroke, |nracran|a| |es|ons, Park|nson's o|sease or sponoy|o||shes|s
can cause severe empy|n or sorae sympoms |n e|oer|y men [28|.
These pa|ens m|h have BPH bu he LUTS are causeo by cono|-
|ons oher han BPH. Search|n or ev|oence o BOO |s manoaory
beore proceeo|n w|h |nvas|ve proceoures o rea ma|e LUTS be-
cause LUTS usua||y canno be reso|veo w|h such proceoures. Ure-
hra| sr|cure or urehra| meaa| senos|s can cause BOO ano LUTS,
espec|a||y |n pa|ens who have hao a prev|ous ransurehra| proceoure.
A oea||eo phys|ca| exam|na|on ano urehra| o||a-a|on can re||eve he
LUTS w|hou necess|a|n an |nvas|ve o|anos|c proceoure.
CONCLUSIONS
LUTS |n men can be causeo by boh b|aooer oysunc|ons ano
b|aooer ou|e oysunc|ons, occurr|n a|one or |n comb|na|on. The
presen|n sympoms o ma|e LUTS are s|m||ar |n pa|ens w|h or w|h-
ou BPO. Many pa|ens w|hou BOO a|so comp|a|n o oysur|a. By
compar|son, urency was h|h|y preva|en |n pa|ens w|h DO ano
DHC, as we|| as |n pa|ens w|h b|aooer ou|e oysunc|ons such as
b|aooer neck oysunc|on ano BPO. B|aooer sympoms are no re||-
ab|e |no|caors o he presence o DO. LUTS |s no useu| or he o|er-
en|a| o|anos|s o BPO or non-BPO |n men. The key sympom o OAB,
Differential diagnosis of male LUTS
S
H. C. Kuo
|.e. urency, canno be useo o make a oe|n|e o|anos|s o DO. The
e|o|o|es o LUTS may |nvo|ve boh b|aooer oysunc|ons ano b|aooer
ou|e oysunc|ons. Accurae o|anos|s o |ower ur|nary rac oysunc-
|on shou|o be baseo on a comprehens|ve urooynam|c suoy, wh|ch
w||| enab|e correc se|ec|on o a herapy ha |s a|meo a he unoer|y-
|n pahophys|o|oy.
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