Disfunción Sexual y Prostatismo

ENFERMEDADES DE LA
PROSTATA
PROSTATITIS
HIPERTROFIA PROSTATICA
CANCER PROSTATICO

La Próstata
Anatomía y Desarrollo

PROSTATA
Anatomía
 La glándula prostática es un órgano
sexual accesorio localizado por debajo
de la vejiga y las ampollas diferenciales
con salida hacia la uretra
 Tiene forma cono invertido y tamaño a la
de una nuez pequeña, cerrada por una
cápsula fibrosa y rodea a la uretra
 En la eyaculación produce un liquido
alcalino que es componente del semen

Anatomy of the prostate gland
Prostatic
urethra
Prostate
Ejaculatory duct
openings
External urethral
sphincter
Bladder
Kirby R et al (Eds) Adapted from
Textbook of BPH 1996

PROSTATA
Estructura
 Se distinguen 4 regiones distintas originadas de
diferentes segmentos de la uretra prostática:
 La zona ventral o anterior, carece de glándulas,
compuesta de tejido fibromuscular
 El resto es tejido glandular (3 zonas):
– Zona periférica (70%): comprende la porción
lateral posterior de la próstata
– Zona central (25%): rodea a los cond. eyac.
– Zona transicional (5–10%):
Kirby R et al (Eds). Textbook of BPH 1996

Lateral section of a normal prostate
Transition zone
Anterior
fibromuscular
area
Peripheral zoneCentral zoneSeminal vesicle
Ejaculatory
ducts
Urethra
Bladder wall

Prostata normal
Central
zone
Peripheral
zoneTransitional
zone

Seccion Transversa
Transitional zone
Peripheral zone
Central zone
Urethra

HISTOLOGIA.
Los estudios de diferentes partes de la próstata
indican que:
 La HPB se origina en el tejido glandular y en la
uretra pre-prostática.
 El Cáncer Prostático se origina primariamente
en la zona periférica donde se aprecian muy a
menudo cambios inflamatorios.

Crecimiento Prostatico. H P B
CAUSAS:
Excesos de masturbaciòn,
Actividad sexual frecuente,
Presencia de enf. Venereas,
Pensamientos eròticos,
Equitaciòn, Ciclismo, Clima frìo

H P B. Factores
 Edad
 Tabaquismo
 Obesidad
 Cirrosis e Ingesta de
alcohol
 Factores Familiares
 Factores Raciales
 Dieta
 Vasectomia y Act. Sexual

Hiperplasia Prostàtica Benigna
 La HPB es la neoplasia
benigna mas frecuente
en el hombre
 Sus cambios patológicos
se encuentran en el 50%
de los hombres de la
quinta década y en 90%
de la novena
 La etiología de HPB es
multifactorial. Es
requisito esencial
tener testículos y
edad

Crecimiento prostatico.
Mecanismo molecular
 Los andrógenos y principalmente la DHT, son
los princ. reguladores del crecimiento y
actividad prostática vía cascada de
interacciones moleculares.
 La testosterona libre se convierte dentro de la
célula en DHT que se une a los receptores
androgénicos (RA) del genoma nuclear.
Denis L et al. 4th International Consultation on BPH 1997

PROGRESION DE HPB
La HPB es siempre una
condicion progresiva

H P B
 Enfermedad mas prevalente en
hombres de 50 a 80años de edad
(48 a 98 por ciento
respectivamente)
 8 por ciento en la poblaciòn en
general

Epidemiologìa de la HPB
(segùn la edad)
100
90
80
70
60
50
40
30
20
00
0
40 45 50 55 60 65 70 75 80
Men (%)
Age (years)
Guess HA et al. Prostate 1990; 17: 241–6

Prevalencia de la HPB
Edad
11%
29%
48%
77%
87%
92%
0
20
40
60
80
100
31–40 41–50 51–60 61–70 71–80 80+
Berry SJ et al. J Urol 1984; 132: 474–9
Prevalence (%)

Prevalencia de la HPB
Edad
0
20
40
60
80
100
40–49 50–59 60–69 70–79
Age (years)
Histroia Clinica
Examen Rectal
9%
27% 27%
51%
42%
69%
57%
80%
Prevalence (%)
(n=1,057)
Arrighi MH et al. Urology 1991; 38 (Suppl): 4–8

H P B. Cuadro Clìnico
PROSTATISMO.
Sindrome Miccional
Con Crecimiento ò Hiperplasia
Por Obstrucciòn

H P B Cuadro Clìnico
FALTA DE CORRELACIÒN ENTRE
VOLUMEN DE LA HIPERPLASIA
Y LA SEVERIDAD DE LOS
SINTOMAS

H P B. Cuadro Clìnico
 PROBLEMAS EN ALMACENAMIENTO Y
LLENADO VESICAL. (sìntomas
irritativos): Nicturia, Frecuencia,
Urgencia con Incontinencia, Disuria.
 PROBLEMAS DE VACIAMIENTO
VESICAL. (sìntomas obstructivos):
Dism. Fuerza del chorro, Retardo en
inicio de micciòn, Pujo, Chorro
Intermitente, Sensaciòn Vaciamiento
incompleto, Retencion urinaria.

Sintomatologia de HPB
Weak stream
Incomplete bladder emptying
Dribbling
Intermittency
Straining
Urgency
Hesitancy
Nocturia
CON HPBSIN HPB
Garraway WM et al.
Br J Gen Pract 1993; 43: 318–21
12.6%
36.8%
10.6%
31.7%
23.1%
42.5%
7.8%
26.6%
13.2%
40.5%
25%
46.6%
11.1%
31.7%
12.3%
40.2%

Sintomatolgìa por HPB
30 20 10 0 10 20 30 40
Wet clothes
Irritability
Dysuria
Frequency
Weak stream
Incomplete emptying
Intermittency
Dribbling
Urgency
Straining
Hesitancy
Nocturia
Inicio Tres años
Symptom
Bother
Percentage of men Lee AJ et al. Eur Urol
1996; 30: 11–17

PROSTATISMO
 FASES
1.-Vejiga de Esfuerzo
2.-Retenciòn Crònica
3.-Distensiòn Vesical

Prostata crecida
Central zone
Peripheral zone
Transitional zone

Prostata Crecida
The normal prostate is
triangular, becoming
rounder as BPH develops
and the transitional zone
expands

Prostata Crecida
 Localizaciòn
Tìpica de la HPB
en la zona
trancisional.
 Desplazamiento
de los lòbulos
central y
perifèrico
Urethra
Transitional
zone
Central zonePeripheral zone

Desarrollo de la HPB
Cambios en la Vejiga y
Complicaciones de
La HPB

La HPB se desarrolla en varios pasos:
 Se induce la hiperplasia microscópica
 Se desarrollan nódulos microscópicos
 Inicia la manifestación clínica de HPB:
– crecimiento prostático
– obstrucción del cuello vesical
– sintomatología del tracto urinario inferior

 Nódulos microscópicos de estroma empiezan a
crecer en la próstata alrededor de los 30-40
años de edad.
 Este crecimiento ocurre alrededor de la zona
trancisional en el región periuretral
desarrollándose hiperplasia glandular.
 Los nódulos varían en tamaño desde varios
mms. A cms.
 Los nódulos continuaran creciendo.
Kirby R et al (Eds). Shared Care for Prostatic Diseases 1995

Desarrollo de HPB
 Se comprime la capa mas externa de la
próstata
 Se crea una cápsula ajustada y por lo
mismo se forman lóbulos.
 El tamaño y posición de los lóbulos en
relación a la vejiga y la uretra, determinara
el tipo y la severidad de los síntomas del
tracto urinario inferior.
 Ocurrirá una obstrucción urinaria si la
próstata crecida estrecha a la uretra.

Vejiga e HPB
 El lóbulo medio se
proyecta dentro de la
base de la vejiga
 La uretra prostática se
estrecha
 La pared vesical forma
trabéculas y
engrosamiento

Efectos de la Obstruccion Urinaria.
 Cambios irreversibles y
engrosamiento de la
vejiga.
 Sangrado (hematuria)
 Diverticulos
 Infecciones Urinarias
repetitivas.
 Càlculos urinarios
 Hidronefrosis (dilataciòn)
 Daño renal

DAÑO RENAL
 Puede ocurrir aùn
con minima
sintomatologìa y la
lesiòn renal no es
siempre reversible

H P B Epidemiologìa
 Focos de Crecimiento
prostatico: 25-30 años
 25 % de varones de 40 años
presentan HPB y 100 % a los 80
 Esto no significa presencia de
enfermedad clìnica.

PROSTATISMO.
Epidemiologìa
 La enfermedad sintomatica se presenta
despues de los 50 años
 Incidencia a los 55-64 años: 30%
 Mas de 64 años: 55%
 El numero de personas con prostatismo
aumentará en cerca del 45 % en los
siguientes 10 años y todavia mas a la
otra decada. (1999)

H P B
 Causa significativa de
deterioro de calida de
vida en gente mayor
 Quienes sufren de HPB
son renuentes a acudir al
médico. (envejec, normal)

Hallazgos de molestias por HPB en la
consulta mèdica
0 10 20 30
Weak stream
Incomplete bladder emptying
Dribbling
Intermittency
Straining
Urgency
Hesitancy
Nocturia twice or more
Grado Sintomatologìa consultada aL doctor
Finding symptom bothersome
9.4%
19.0%
4.1%
16.3%
4.5%
28.3%
4.1%
12.8%
4.7%
20.4%
6.3%
30.7%
6.0%
16.6%
4.2%
19.0%
Garraway WM et al.
Br J Gen Pract 1993; 43: 318–21

Prevalencia de sintomatologia
moderada a severa (I-PSS ≥8)
 Includes both hospital/clinical-based and community-based studies
 Community-based study (n=2,115) men aged 40–79 years
Prevalence (%)
0
10
20
30
40
50
60
50–59 60–69 70–79
Age (years)
Asia USA Canada
29% 31%
15%
40%
36%
27%
56%
44%
31%

Prevalencia de Sintomas Severos
0 2 4 6 8 10 12 14 16 18
40-49
50-59
60-69
70-79
28% a los 70 años y 13% a los 40-49

Interferencia con las
actividadesPercentage of men in whom urinary symptoms affected living
activities at least some of the time
Avoids visits to theatre, cinema,
church etc
Avoid outdoor sports
Avoid places without toilets
Not getting enough sleep
Cannot drive for 2 hours
Limit fluid before bedtime
Limit fluid before travel
13.4%
29.9%
18.4%
34.7%
8.0%
21.0%
10.3%
27.1%
13.2%
32.4%
6.2%
12.8%
6.7%
15.1%
CON HPBSIN HPB
Garraway WM et al.
Br J Gen Pract 1993; 43: 318–21

HPB. Calidad de Vida
0.00
0.10
0.20
0.30
0.40
0.50
Degree of
bother
Degree of
interference
Degree of
worry
OGWB
scale
Sexual
worry
Sexual
satisfaction
No = 0
Leve = 1–7
Mod. A Severa = 8–35
Age adjusted means
(s.e.) on 0–1 scale
Girman CJ et al. Urology 1994; 44: 825–31

Diagnostico
 Historia Clìnica; Sintomas y
Severidad, Antecedentes trauma
uretral y herediatrios, Enf,
Neurològicas, Hàbitos, etc.
 Determinaciòn del volumen
prostatico.
 Examenes de laboratorio y
Gabinete

Próstatismo
Determinación del volúmen
prostático

Determinación del Volúmen
Prostático
 3 técnicas principales:
–Examen digital rectal
–USG transrrectal
–Resonancia magnética

Determinación del Volúmen
Prostático
 La exactitud del tacto digital
depende de la experiencia del
examinador
 Es mas seguro el uso de USG
transrrectal para determinar
el volumen prostático

Volùmen Prostático
 El examen digital sobrestima el
tamaño prostatico en prostatas de
mas de 30 ml.
 El USG transrrectal y la resonancia
magnetica son invasivos y caros
 El APE sérico es una medida util

H P B Diagnòstico
 ANTIGENO PROSTATICO
ESPECIFICO
 EXAMEN GENERAL DE
ORINA
 QUIMICA SANGUINEA

TRATAMIENTO
BASADO EN LA INTENSIDAD DE LOS SINTOMAS Y LOS
CAMBIOS EN LA CALIDAD DE VIDA:
 Sìntomas Leves: Expectante,
Revisiones periòdicas
 Sintomas Moderados: Tx mèdico ò
quirùrgico.
 Sìntomas Severos: Cirugìa

CANCER DE LA PROSTATA
PROBLEMA DE SALUD MUNDIAL.
AUMENTA PREVALENCIA CON LA
EDAD:

CANCER PROSTATICO
 PRIMER LUGAR EN EEUU (8%) Y EN
MEXICO (25%) EN VARONES DE
CUALQUIER EDAD
 EN LA POBLACION GENERAL: 11%
(TERCER LUGAR EN FRECUENCIA)
 SEGUNDA CAUSA DE FALLECIMIENTOS
EN VARONES 50 AÑOS EN EEUU
(PRIMERO EN SUIZA)
 INCIDENCIA: 50a : 30% 80a : 70%
90a: 90%

CANCER PROSTATICO
CUADRO CLINICO
 ASINTOMATICO EN ETAPAS INCIPIENTES
 HEMATURIA, SINTOMAS OBSTRUCTIVOS Ò
SINTOMATOLOGIA POR METASTASIS EN
ETAPAS AVANZADAS

CANCER PROSTÀTICO
DIAGNOSTICO
 PRIMERA LÌNEA DE
ESTUDIOS DE TAMIZAJE Y
ESCRUTINIO DEL CaP: APE
y Exploracion Digital rectal
de la Prostata

CANCER PROSTATICO
Antigeno Prostàtico Especifico
 MARCADOR ONCOLOGICO SECRETADO
POR PROSTATA EN SEMEN
 DX INICIAL DEL CANCER Y
SEGUIMIENTO TX
 ES ESPECIFICO PARA LA PROSTATA
MAS NO PARA CANCER
 VALORA RIESGO DE CA. NO PRUEBA
DX

Numbers of TURPs per 1,000 men
≥50 years of age per year
5.55.9*United Kingdom†
6.89Germany
5.510Denmark
813*Canada (Alberta)
8.914France
5.815United States
19951989Country
†
Men 45 years and older
*1990 data

Etiologia de la HPB
 The molecular processes underlying the
development of BPH are not completely understood,
but androgens and age play a central role
 Several hypotheses have been proposed to explain
the pathogenesis of BPH:
– dihydrotestosterone (DHT) hypothesis
– oestrogen–testosterone imbalance
– stromal–epithelial interactions
– reduced cell death
– stem cell theory

Aetiology of BPH – dihydrotestosterone
Dihydrotestosterone (DHT) is the main androgen
responsible for prostate growth
Two isoenzymes of
5α-reductase
have been identified
5α-reductase
inhibitors
suppress DHT
formation
Adapted from Kirby R et al (Eds).
Shared Care for Prostatic Diseases 1995

The stem cell concept

HPB
 La HPB en forma macroscopica es la de
nódulos de tamaño variable de color gris a
amarillento
 Los nódulos se componen de musculo liso,
epitelio y tejido fibroso en cantidades variables
 Varía la proporción de estroma a epitelio en la
HPB, lo que sugiere la determinación de
sintomatología en un paciente prostático

HPB. Fase Patológica
 Inician cambios histologicos en la prostata por
una tranformació neoplastica de las células
prostaticas
 Estas celulas se comportan como celulas
embriónicas
 Los conductos prostáticos se organizan
formando nódulos de estroma y epitelio
glandular

HPB. Fase macrscópica
 No todo el tejido hiperplasico progresa a la fase
macroscópica en estos pacientes
 La prostata se engrosa haciéndose aparente la
sintomatología en algunos hombres
 A medida que el tejido glandular crece la capa
externa se comprime, creandose una cápsula
dura que forza a la glandula a formar lobulos
 El tipo y severidad de los síntomas dependerá
del tamaño y posición de los lobulos en
relación a la vejiga y la uretra

Development of BPH
Histological appearance of BPH

Enlarged prostate: histology
Transverse sections
through the prostate

BPH tissue
The two layers of
epithelial cells, the
basal cells (A) and the
secretory cells (B), are
visible
Also note that the
secretory cells are tall
and columnar in
appearance
B
B
A
Stroma
H and E stain of BPH tissue (200x magnification)

BPH tissue
This shows extensive
infolding of the duct
This is typical of BPH
tissue and is caused by
the stroma pushing
against the duct

BPH tissue
This shows the
typical lobe-like
architecture of BPH
nodules and the
associated blood
vessels (A)
A
A
A

Bladder changes
 Flow is maintained in the early phases of outflow
obstruction as hypertrophy of the detrusor muscle
allows an increase in detrusor pressure
 As outflow obstruction progresses, smooth muscle
hypertrophy occurs, followed by connective tissue
infiltration and reduced parasympathetic innervation
 Impaired emptying results, caused by decreased
compliance in the bladder wall and secondary
detrusor instability, due to the previous events
 Ultimately these changes translate into the
persistent symptoms of frequency, urgency and
urge incontinence

Bladder changes
 It has been postulated that increasing amounts
of extracellular matrix (ECM) components such
as collagen are deposited in the bladder,
leading to impaired emptying
 ECM components are thought to be produced
by the detrusor smooth muscle in both the
normal and abnormal bladder
 Alteration of ECM expression is thought to be a
predominant pathophysiological feature in long-
term obstruction

Bladder changes
Rabbit model of obstruction
 Rapid increase
in bladder mass
 Bladder
function
impairment
 Smooth muscle
hypertrophy
1–2 weeks
Rapid and
full bladder
function
restoration
Partial
recovery
of bladder
function
Obstruction
removed
Obstruction
Initial period of
obstruction
removed
Compensated stage
Decompensated stage
 Bladder mass
stabilises
 Bladder emptying
80–90% less than
control
 Rapid increase in
bladder mass
 Progressive loss
of ability of
bladder to empty Kirby R et al (Eds). Textbook of BPH 1996

BPH – a progressive condition
 Progression of BPH can be defined in a number of ways:
– increase in prostate volume
– worsening of LUTS, bother, interference with daily
activities and quality of life
– deterioration in urinary flow rate
– increased risk of acute urinary retention (AUR)
– increased risk of needing surgery
 The risk of progression differs between patients
 Stratification by baseline parameters can be used to
predict risk of progression and aid with management
decisions

Key studies supporting BPH as a
progressive condition
Cohort studies:
 Arrighi et al (1990), n=1,057
 Barry et al (1997), n=500
 Lee et al (1996), n=217
 Olmstead County study, n=2,115
 Meigs et al (1999), n=51,529
Treatment studies:
 Flanigan et al (1998), n=556
 PLESS trial (n=3,040)

Smaller studies supporting BPH as a
progressive condition
 Williams et al (1999), n=128
 Cucchi et al (1994), n=34
 Bosch et al (1994), n=502
 Ball et al (1981), n=107
 Birkhoff et al (1976), n=156

Progression of BPH
Growth of the prostate

Development of BPH: Early
Bladder
Muscle
surrounding
upper prostate
BPH
Prostatic urethra
Prostate
tissue
Surgical
capsule

Development of BPH: Intermediate
BPH
Narrowed
prostatic urethra
Prostate
tissue
Surgical
capsule

Development of BPH: Late
BPH
Severely narrowed
prostatic urethra
Prostate
tissue
Surgical
capsule

Mean total prostate volume
by decade of life
50–59 60–69 >70
0
10
20
30
40
50
60
70
80
Volume (ml)
Age (years)
Roehrborn CG et al.
J Urol 2000; 163: 13–20

PLESS – patterns of prostate growth
(untreated BPH)
McConnell JD et al.
N Engl J Med 1998; 38: 557–63
Baseline
Years
Prostate volume (mean % change from baseline)
20
10
–20
0
–10
1 2 3 4

PLESS – Absolute prostate growth by
year and PSA tertile (untreated BPH)
0
2
4
6
8
10
12
14
12 months 24 months 36 months 48 months
PSA 0.2–1.3 (n=52)
PSA 1.4–3.2 (n=65)
PSA >3.3 (n=47)
Change from
baseline (ml)
Roehrborn CG et al. J Urol 2000; 163: 13–20

Patterns of prostate growth
 Olmsted County study:
– mean overall annual growth was 0.6 ml
over a period of 3.5 yrs, ranging from 0.4 ml in men
aged 40–59 yrs to 1.2 ml in men aged 60–79 yrs
– seven-year follow-up showed an annual mean
increase in volume of 1.9%
 PLESS trial:
– mean annual growth was 1.8 ml over a period of 4
years in placebo-treated patients, ranging from 1.45
ml in men aged 50–59 years to 2.4 ml in men aged 70–
79 years
Jacobsen SJ et al. J Urol 1999; 162: 1301–6
Rhodes T et al. J Urol 2000; 163 (4 Suppl): 249
Roehrborn CG et al. J Urol 2000; 163: 13–20

Progression of BPH
PSA as a marker of prostate volume

PSA as an indicator of prostate volume
 Data from 2,270 patients with BPH show that:
– increases in PSA and age are associated
with increases in prostate volume, but the
relationship with PSA is independent
– a log-linear relationship between PSA and
prostate volume exists
Hochberg DA et al. Prostate 2000; 45: 315–9

Total prostate volume stratified by
PSA ranges (population means)
Volume (ml)
PSA range (ng/ml)
1.5–2.0
2.0–2.5
2.5–3.0
3.0–3.5
3.5–4.0
4.0–5.0
5.0–6.0
6.0–8.0
8.0–10.0
0
10
20
30
40
50
60
70
80
Roehrborn CG et al.
Urology 1999; 53: 581–9

Linear regression of total prostate volume
stratified by PSA ranges and age
TPV (ml)
80
PSA range (ng/ml)
1.5–2.0
2.0–2.5
2.5–3.0
3.0–3.5
3.5–4.0
4.0–5.0
5.0–6.0
6.0–8.0
8.0–10.0
40
45
50
55
60
65
70
75
Age
50–59 yrs
60–69 yrs
>70 yrs
Roehrborn CG et al.
Urology 1999; 53: 581–9

Progression of BPH
Deterioration of urinary flow rate

Deterioration of urinary flow rate –
key studies
Cohort study:
 Olmsted County study (n=2,115)
Treatment study:
McConnell JD et al. N Engl J Med 1998; 38: 557–63
Roberts RO et al. J Urol 2000; 163: 107–13

PLESS trial – Maximum flow rate
(untreated BPH)
Maximum urinary flow rate
(mean change from baseline)
1.0
0.0
0.5
Baseline
Years
1 2 3 4

Olmsted County Study – Peak urinary
flow rates by age
0
5
10
15
20
25
40–49 50–59 60–69 70–79
Baseline
+1 year
+2 years
+3 years
Peak flow rate
(ml/sec)
Age (years)

PLESS trial – Maximum flow rate
by PSA tertile (untreated BPH)
Month
∆ Qmax
2.0
1.5
1.0
0.5
0.0
-0.5
-1.0
-1.5
-2.0
0 4 8 12 16 20 24 28 32 36 40 44 48
0.1–1.3
1.4–3.2
3.3–12.0
Roehrborn CG et al.
Urology 1999; 54: 662–9
PSA (ng/ml)

Deterioration of urinary flow rate
Conclusions
 Data from the Olmsted County study
demonstrate a deterioration in urinary flow
with age
 In contrast, data from the PLESS trial do not
demonstrate a decrease in flow in placebo-
treated patients over a period of 4 years
 The differences between urinary flow rates by
baseline PSA tertile in PLESS are significant;
therefore baseline PSA can aid prediction of
change in flow
Roehrborn CG et al. Urology 1999; 54: 662–9

Progression of BPH
Deterioration of lower urinary tract
symptoms and Quality of Life

Deterioration of LUTS and QoL –
key studies
Cohort studies:
 Lee et al (1996), n=217
 Olmsted County study, n=2,115
 UreEpik study,n=4,800
Treatment studies:

PLESS – IPSS overall (untreated BPH)
Baseline
Years
Quasi-AUA symptom score
(mean change from baseline)
0
–1
–2
–3
1 2 3 4
McConnell JD et al. N
Engl J Med 1998; 38: 557–63

Olmsted County Study – progression
of symptoms over 4 years
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
40–49 50–59 60–69 70–79 40–79
Age (years)
*
*
*
*p<0.001 versus baseline
Change in AUA symptom
index from baseline

PLESS – IPSS by PSA tertile
(untreated BPH)
Month
0.0
4 8 12 20 24 28 32 36 44 48
-0.5
-1.0
-1.5
-2.0
-2.5
-3.0
0 4016
Change in IPSS
Roehrborn CG et al.
Urology 1999; 54: 662–9
0.1–1.3
1.4–3.2
3.3–10.0
PSA (ng/ml)

PLESS – Bother score* (untreated BPH)
Mean change in
bother score
Year of follow up
1 2 3 4
-4
-3
-2
-1
0
PSA: 0–12 ng/ml
Bruskewitz R et al.
Urology 1999; 54: 670–8
0
*Extended response option version of the BII

PLESS – Bother score by PSA tertile
(untreated BPH)
30 1 2 4
Mean change
in bother score
PSA (ng/ml) 1.4–3.2
PSA (ng/ml) 3.3–12
PSA (ng/ml) 0.0–1.3
-3
-2
-1
0
-0.5
-1.5
-2.5
Serum PSA (ng/ml)
Bruskewitz R et al.
Urology 1999; 54: 670–8

The UrEpik Study – Percentage of men with
moderate to severe symptoms (IPSS 8–35)
Boyle P et al.
J Urol 2000; 163 (S4): 208
0
10
20
30
40
50
40–49 50–59 60–69 70–79
Age group
Percentage
Boxmeer (NL)
Birmingham (UK)
Auxerre (FR)
Seoul (KR)

The UrEpik Study – Health care visits
by age and IPSS for any reason
0
2
4
6
8
10
0–7 8–19 20–35
IPSS groups
12
14
40–49 years
50–59 years
60–69 years
70–79 years
Mean number of health care
visits per person/year
Boyle P et al. Eur Urol 2000; 37 (S2): 402

Deterioration of LUTS and QoL
Conclusions
 Data from the Forth Valley study demonstrate
deterioration of symptoms and degree of bother
over 3 years, findings confirmed by the Olmsted
County and PLESS data
 Data from PLESS demonstrate that men with
higher PSA levels are at greater risk of
progressive symptoms and increased bother
 The UrEpik study demonstrates worse
symptoms in older men, which correlate with
increased numbers of health care visits
Lee AJ et al. Eur Urol 1996; 30: 11–17; Jacobsen SJ et al. J Urol 1996; 155: 595–600;
McConnell JD et al. N Engl J Med 1998; 38: 557–63; Roehrborn CG et al. Urology 1999; 54: 662–9
Bruskewitz R et al. Urology 1999; 54: 670–8; Boyle et al (2000)

Progression of BPH
Risk factors for AUR and need for surgery

Risk factors for AUR and need for
surgery – key studies
Cohort studies:
 Arrighi et al (1990), n=1,057
 Lee et al (1996), n=217
 Olmsted County study, n=2,115
 Meigs et al (1999), n=51,529
Treatment studies:
 Flanigan et al (1998), n=556

Baseline Relative Confidence
variable risk intervals
Age (years)
40–49 Reference category
50–59 4.21.2–14.8
60–69 4.01.1–14.8
70–79 3.10.8–12.3
Symptom severity score
None/mild (≤7) Reference category
Moderate/severe (>7) 5.62.6–11.9
Olmsted County Study – baseline variables
and risk for treatment – I

Bladder changes
 The LUTS that accompany BPH can be exacerbated
by changes occurring in the bladder as a
consequence of obstruction of the urethra, which
can be dynamic, static, or a combination of both
 Ultimately this can lead to a loss of bladder
compliance and involuntary detrusor contractions;
this leads to more severe urinary tract symptoms
 In addition, obstruction causes the bladder to
undergo compensatory changes, and gross
anatomical, histological, cellular and molecular
alterations occur in the bladder wall

Olmsted County Study – baseline
variables and risk for treatment – II
Peak flow rate (ml/sec)
>12 Reference category
≤12 2.81.4–5.5
Prostate volume (ml)
≤30 Reference category
>30 2.31.1–4.7
Serum PSA (ng/ml)
≤1.4 Reference category
>1.4 2.11.1–4.2

Need for surgery by baseline risk
factors (n=1,057)
0
5
10
15
20
25
30
35
40
0 1 2 3
Number of risk factors
Risk factors: Change in size & force of stream,
sensation of incomplete emptying, prostate
enlargement on DRE
% requiring prostatectomy
Arrighi HM et al. Prostate 1990; 16: 253–61

Outcome of BPH patients randomised
to watchful waiting versus TURP
% of WW patients crossing-over to TURP
30
25
20
15
10
5
0
0 1 2 3 4 5
Elective cross-overs
high bother
Elective cross-overs
low bother
Post-treatment failure
cross-overs high bother
Post-treatment failure
cross-overs low bother
Years of follow-up
Flanigan RC et al. J Urol 1998; 160: 12–17

Age (years)
50–59 0.90.4–2.4
60–69 2.10.9–4.7
70–79 4.82.2–10.6
AUA Symptom Index
>8 2.31.3–4.0
Peak flow rate (ml/sec)
>12 Reference category
≤12 2.11.2–3.8
Olmsted County Study – relative risk
of AUR by baseline factors

Risk of AUR by baseline prostate
volume and serum PSA
(untreated patients over 2 years)
0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
<40ml ≥40ml <1.4ng/ml ≥1.4ng/ml
Volume Serum PSA
% with retention
Marberger MJ et al. Eur Urol 2000; 38: 563–8

Incidence of AUR by age
0
2
4
6
8
10
12
14
16
45–49 50–59 60–69 70–79 80–83
No of AUR events per
1000-person years
Age (years) Meigs JB et al.
J Urol 1999; 162: 376–82

Incidence of AUR or surgery by PSA and
volume tertiles (untreated patients)
Baseline PSA tertiles (ng/ml)
0–1.3 1.4–3.2 3.3–12
Patients (%)
0
4
8
12
16
20
24
14–41 41–57 58–150
Baseline prostate volumes (ml)

Conclusions – I
 Do outcome measures change over time in
patients with BPH?
There is consistent evidence from
methodologically robust studies for:
– increases in prostate volume
– worsening of lower urinary tract symptoms
(LUTS), bother, interference, and quality of life
– deterioration in urinary flow rate
– increased risk of acute urinary retention (AUR)
– increased need for surgery

Conclusions – II
 Which risk factors have predictive value for
patients with a high risk of BPH progression?
There is strong evidence for:
– serum PSA
– age
Good evidence requiring confirmation for:
– prostate volume
Evidence exists for:
– baseline symptoms
– baseline maximum urinary flow

BPH diagnosis
BPH clinical presentation

Clinical presentation
LUTS may be divided into two broad categories:
 Storage symptoms (irritative symptoms) which
tend to have a greater influence in provoking
patients to seek medical advice
 Voiding symptoms (obstructive symptoms) –
physicians tend to be more concerned about
these symptoms, which are more likely to result
in serious sequelae

Clinical presentation
 BPH is by far the most common diagnosis in
men presenting with prostate problems
 Physicians are primarily concerned with making
an accurate differential diagnosis, in particular
to exclude prostate cancer or to make an early
diagnosis
 If left undiagnosed and untreated, BPH can
progress to complete blockage of the urethra
and acute urinary retention (AUR). This
necessitates hospitalisation and catheterisation
to remove accumulated urine, and often
subsequent surgery

Initial evaluation of LUTS
 Medical history
 IPSS questionnaire
 Bolter score
 Physical examination and digital rectal
examination
 Urinalysis
 Serum PSA
 Voiding diary
Chatelain Ch et al. 5th International Consultation on BPH 2000

Medical history
A detailed medical history should be performed
to identify other causes of voiding dysfunction
and comorbidities that may complicate treatment.
The focus should be on:
 The nature and duration of symptoms
 Previous surgical procedures
 General health issues
 Medications taken by the patient
 Fitness for possible surgical procedures

Physical examination
 An examination should be performed to assess:
– the suprapubic area to rule out bladder
distension
– overall motor and sensor function
 A digital rectal examination (DRE) to evaluate
the anal sphincter tone and prostate gland with
regard to approximate size, consistency, shape
and abnormalities suggestive of prostate cancer

Standard tests
Standard tests:
 Urinalysis by dipstick and examination for
sediment following centrifugation
 Serum prostate specific antigen (PSA)
 Voiding diaries (frequency - volume chart),
especially where nocturia is the dominant
symptom

Optional tests
Optional tests:
 Flow rate recording
 Residual urine
 Pressure - flow studies
 Transabdominal or transrectal ultrasound
 Ultrasonography or intravenous urography of
the upper urinary tract
 Endoscopy of the lower urinary tract

Digital rectal examination (DRE)
Clinical parameters that can be assessed by DRE include:
 Size: transverse, longitudinal and posterior protrusion
 Consistency: slight pressure over the surface to detect
whether:
– smooth or elastic – normal
– hard or woody – may indicate cancer
– tender – suggests prostatitis
 Mobility: attempts made to move the prostate up and
down to the sides. A malignant gland may be fixed to
adjacent tissue
 Anatomical limits: finger used to try to reach lateral
and cranial borders – seminal vesicles should be
impalpable; induration of these suggests malignancy

Urinalysis
 Urinalysis by ‘dipstick’ or microscopic
examination of sediment will allow BPH to
be distinguished from UTI or bladder cancer
and should be performed in all men presenting
with LUTS
 If positive, urine microscopy and culture should
be performed and further imaging and
evaluation of the renal tract considered

Uroflowmetry
 This is a technique for electronically recording the
rate of urine flow and the volume of urine passed
during micturation
 It is a simple, well used, useful, independent
measure, which is helpful in:
– distinguishing between BPH and urethral
strictures or prostatitis
– predicting which patients will benefit from
surgery
– identifying the need for invasive urodynamic
studies
– to help distinguish bladder problems from BPH
 Most often used as a rough screening procedure, as
a way to assess treatment outcome, and as a
technique for monitoring the progression of disease

Uroflowmetry
 The flowmeter device measures the quantity of fluid
passed per unit time
 In addition, several different values can be
calculated
– voided volume: the total amount of urine voided
– max flow rate (Qmax): the fastest rate at which
urination occurs
– average flow rate = voided volume/flow time
– time to maximum flow: time between the onset of
micturation and when peak flow occurs
– flow time: the time over which measurable urine
flow occurs

Uroflowmetry
 Qmax is the most useful uroflow measure used
and provides a good indication of whether a
patient is obstructed or not
 Patients with a value:
– <10 ml/sec are generally considered
obstructed
– >15 ml/sec are judged unobstructed
– in the range of 10–15 ml/sec are equivocal
 Accuracy is improved if the voided volume
exceeds 150 ml

Uroflowmetry
Unobstructed Obstructed
Detrusor underactivity Urethral stricture

Uroflowmetry: unobstructed
Voided volume Vcomp 158.0 ml
Average flow rate Qave 12.2 ml/s
Max flow rate Qmax 18.5 ml/s
Time to max flow TQmax 4.8 s
Flow time TQ 12.5 s
Voiding time T100 13.5 s
 70-year-old man
 Normal flow
trace

Uroflowmetry: obstructed
133.0 ml
2.7 ml/s
7.0 ml/s
6.2s
48.5s
68.0s
Voided volume V comp
Average flow rate Q ave
Max. flow rate Qmax
Time to max. flow TQ max
Flow time TQ
Voiding time T100
 70-year-old man
 Moderate obstruction
due to BPH
 Reduced average and
peak flow
 Prolonged duration

Uroflowmetry: urethral stricture
Voided volume Vcomp 567 ml
Average flow rate Qave 4.9 ml/s
Max. flow rate Qmax 5.5 ml/s
Time to max. flow TQmax 0.5 s
Flow time TQ 115.0 s
Voiding time T100 117.0 s 50-year-old man
 Plateau-shaped trace
 Similar Qmax and Qave
 Long duration
Voiding time

Uroflowmetry: detrusor underactivity
Voided volume Vcomp 356ml
Average flow rate Qave 10.0ml/s
Max. flow rate Qmax 17.6ml/s
Time to max. flow TQmax 6.0s
Flow time TQ 34.0s
Voiding time T100 35.0s
 50-year-old man
 Symmetrical trace
 Variable TQmax

Further tests
Further examination and tests can be performed if these
are considered appropriate, these are shown below:
Prostatic biopsy (if rectal exam
and/or PSA warrant it)
Transrectal ultrasound of the
prostate (to assess prostate volume
and reveal early neoplasia)
Bladder residual urine volume
(by transabdominal
untrasound)
Pressure/flow urodynamics (to
assess the degree of bladder outlet
obstruction and to identify any
detrusor impairment)
Uroflowmetry
(Assesses urinary flow rate)
Invasive testsNon-invasive tests

Post-void residual urine volume
(PVRV)
 PVRV measurement is performed non-
invasively using transabdominal ultrasound
 It can be useful in assisting with treatment
decisions but should not be used alone to
diagnose BPH
 Patients found to have a large PVRV should
receive active treatment, otherwise they may be
more likely to develop AUR or fail conservative
therapy

Post-void residual urine volume
(PVRV)
 PVRV measurement can also be useful for
monitoring improvement or worsening of BPH
in non-treated patients
 Although an increased PVRV may be indicative
of obstruction, more than one measurement
should be made because variation has been
known to occur between voids

Urodynamics
 These are the only means by which outflow
obstruction can be diagnosed
 It is expensive and invasive, involving the
introduction of a small catheter, either urethrally
or suprapublically, to measure detrusor
pressure within the bladder (generated by the
contracting bladder muscle minus rectal
pressure)
 It can can be used to distinguish outflow
obstruction from impaired detrusor contractility
 It has been suggested that this technique
should be confined to patients for whom
surgery to relieve obstruction is being
considered

Hiperplasia Prostatica Benigna
Epidemiology

BPH - an increasing problem
Humanistic burden of BPH

Estimates of total costs of BPH surgical
treatment (1990)
2.918.6024.906Sweden
0.6756.7037.800France
5.579.9055.670Belgium
2.2842.4096.430England
3.72123.54459.600Japan
8.88259.602304.500United States
Cost per
capita ($)
Population
(million)
US dollars
(million)
Country
Cockett AK et al. 2nd International Consultation on BPH 1993

Level of negative well-being experienced
during the past month
<0.0012.214.2
Worry about urinary function
becoming worse
<0.0019.029.4
Embarrassed by urinary
function
<0.0120.928.3
Worried about sexual
function
<0.014.89.0
Worried about prostate
cancer
<0.0018.731.1
Worry/concern: urinary
function
<0.0510.514.0Bothered by nervousness
p value*
BPH absent
(%)
BPH present
(%)
Indices of general
well-being
Tsang KK & Garraway WM. Prostate 1993; 23: 1–7*Chi-square test

Effect of BPH on Quality of Life – SF-
36
Hunter DJW et al. Urology 1995; 45: 962–71
0
20
40
60
80
100
SF-36 domains
Physical
functioning
Physical
role
Bodily
pain
VitalityEmotional
role
Social
Function-
ing
Mental
health
General health
perception
Men 55–65 years, with moderate
and severe urinary symptoms
Healthy men 55–64 years
Mean scale scores

BASURA DE HPB
 DE AQUÍ EN ADELANTE SON CUADROS DE
ARRIBA DESECHADOS PARA LA PLATICA DE
ENFERMEDADES DE LA PROSTATA

5 alpha-reductase enzymes
 Occurs as two isoenzymes (type 1 and type 2),
which are hydrophobic proteins
Genital tissue
Seminal
vesicles
Liver
Non-genital skin
Scalp
Enzyme
location
Chromosome 2Chromosome 5
Gene
location
254 amino acids259 amino acidsSize
Type 2Type 1
Russell DW & Wilson JD. Ann Rev Biochem 1994; 63: 25–61

Hormones and prostate growth
 Hormones play a key role in the development and
functional activity of the prostate with free non-protein-
bound testosterone (T) being the active moiety which
enters prostate target cells
 The testes synthesise and secrete 30% of plasma
oestrogens, although a major proportion are also
formed from androsteredione and T by aromatisation
 In a younger man, free T is approx 2%, which
decreases to 1.25% by the 8th decade. Total T is
approx 30–40% of a 25-year-old’s level
 90–95% of T is produced by the Leydig cells of the
testes; T levels decrease with increasing age and a
decrease in the number of Leydig cells

Variability of prostate volume –
Determination by TRUS and MRI
 The mean variability of TRUS determination has
been reported to be 1.3–3.4%
 No studies have investigated the natural
variability of prostate volume, which may
explain some of the variability observed
Aarnink RG et al. B J Urol 1996; 78: 219–23

HISTOLOGIA
 Se identifican dos diferentes compartimentos
histológicos: un estroma fibromuscular y un
epitelio acino-ductal.
Tienen numerosos tipos celulares.
 Las células ductales se encuentran soportadas
por una matrix de estroma y secretan el liquido
prostático hacia la luz de los conductos.

HISTOLOGIA
 La zonas central y periférica de la próstata son
diferentes histológicamente.
 La zona central tiene mas epitelio con nódulos
glandulares mas grandes de contorno irregular.
 La zona periférica tiene un abundante estroma
de trama mas holgado y haces musculares
ordenados al azar
 En la zona trancisional predominan los haces
de músculo liso compactado.

Epitelio de la próstata.
 Las células columnares secretoras revisten
todo el sistema de conductos acinares en cada
zona prostática.
 Las células basales permanecen paralelas a la
membrana basal y separan de ella a las células
secretoras.
 Las células basales se dividen para dar origen a
células maduras secretoras.

Epitelio de la prostata.
 Las células secretoras producen los siguientes
componentes del semen:
– Ácido cítrico
– Fosfatasa ácida
– Fibrinolisina
– Antígeno prostático especifico

Endocrinologia
 La DHT es el andrógeno intracelular activo
responsable de la morfogénesis de la próstata en el
feto.
 En ratas, la enzima 5-alfa reductasa (5-AR) se
localiza en el epitelio basal desde el primer día de
gestación.
 El epitelio lumninal aparece en el 5o. Y 10o. Días
después de la aparición de la 5-AR
 El mesenquima periductal se diferencia en músculo
liso en el tercero a quinto días lo que indica que las
células pueden ser blancos importantes para la
morfogénesis.

La prostata
Crecimiento prostatico

Desarrollo
 En el recién nacido la glándula es parecida a
una estructura de músculo liso.
 Temprano aparecen cantidades mínimas de T
(30–60 dias posnatal), (requisito para el
crecimiento normal de la prostata debido a una
alteracion de las propiedades de las celulas
madres prostaticas. El numero de celulas
madres determina el tamano de la glandula.
 Esta T impactara en el futuro crecimiento
anormal de la glándula.

Development of the prostate:
Formation of the kidney
Hindgut
Allantois
Cloaca
Mesonephric
tissue
Ureteric
bud
Mesonephric
gut
Mesonephric
blastema
Urorectal
septum

Ascent of the kidney
Bladder
Gonad and remnants
of mesonephros
Phallus
Urogential
sinus
Metanephros
Ureter
Rectum

Formation of the prostate
Seminal vesicle
Prostate and
membranous
urethra
Urachus
Penile
urethra
Prostate
gland
Ductus
deferens
Anorectal
canal

Palpación digital de la próstata
0 5 10 15 20 25 30 35
% underestimation
30-39ml
40-49ml
> 50ml
Prostate volume

RESONANCIA MAGNETICA
T2 weighted images show
the zonal anatomy of the
prostate

Crecimiento prostatico
 Testosterone (T) is the
principal androgen
secreted by the testis
 T is converted to DHT
by the enzyme 5α-
reductase (5-AR)
 DHT is the active
intracellular androgen
that has the major
androgenic effect
 This provides the
scientific basis for
the advent of 5-AR
inhibitors for the
management of BPH

Epidemiology
 The lack of widely accepted diagnostic criteria
has hindered the epidemiological study of BPH
 Confusing terminology and the features
of BPH have made prevalence difficult to
determine accurately
 In most cases prevalence is based on
histological autopsy findings or the clinical
relevance of lower urinary tract symptoms

Mecanismo molecular.
 El proceso de unión de la DHT al RA produce
dimerización en una proteína (hsp-90) y
complejo RA-DHT.
 Este complejo induce a un segmento del DNA
del genoma, trascripción de genes andrógeno-
inducibles expresión de APE y otros factores
del crecimiento y estimulación en el
crecimiento y división de las células estromales
y epiteliales
Crecimiento prostático

Receptores Androgenicos
 La cantidad de receptores androgénicos refleja
el grado de actividad androgénica durantes el
desarrollo normal de caract. sexuales masc.
 Después de la pubertad existe disminución en
la sensibilidad al estimulo androgénico en todo
tejido dependiente de ellos. En la próstata
queda alta .
 Los RA de alta afinidad son numerosos en el
epitelio que en el estroma

Receptores Androgénicos
 La combinación de niveles consistentes de
DHT y la expresión continua de receptores
androgénicos produce crecimiento sostenido
de la próstata, como parte del proceso normal
del envejecimiento.

Hormonas y Crecimiento prostático
 DHT es el andrógeno activo
 Aunque los niveles de T disminuyen con la
edad, la DHT permanecen elevados
 DHT (T) también se sintetizan en las glándulas
suprarrenales
 Ciertos metabolitos de la DHT pueden provocar
efectos estrogénicos débiles

Factores de crecimiento prostático
 Componentes epiteliales y del mesenquima
prostático expresan numerosos factores de
crecimiento:
– Estimuladores de los factores de crec:
epidérmico (EGF), de los fibroblastos (FGF),
parecido a la insulina (IGF) y el factor alfa
transformador (TGF-α)
– Inhibidores: factor beta transformador o
apoptosis (TGF-β)

Factores de Crecimiento y desarrollo
de la próstata
 Numerosos factores de crecimiento y de receptores
están bajo la influencia androgénica debido a las
interacciones DHT/RA–DNA
 Esto provoca una balance entre la liberación de
factores estimulantes y factores inhibitorios (TGF-
beta)
 La castración es la forma mas florida de la
apoptosis (resultado de la expresión disminuida de
factores estimuladores y aumento de los inhibidores
 La interacción de los factores de crecimiento
determina finalmente la cantidad de tejido glandular
y estromal en la HPB

Variability of prostate volume –
Determination by TRUS and MRI
 In a phase III N American finasteride study, 86%
of the reported variability of MRI-measured
prostate volume was between-patient variability
 In the same study, only 43% of patients had 2
consecutive determinations within ±10%
Jepsen JV et al. J Urol 1998; 160: 1689–94

The UrEpik study is a prospective, multinational, cross-
sectional, urology, epidemiological study in Europe and
Korea, funded by an unrestricted research grant from
GlaxoSmithKline
Primary aims:
 Determine the impact of BPH-associated symptoms
on QoL of patients and their partners
 Quantify economic and QoL burden of UI and MED
 Enhance understanding of these disorders
The UrEpik Study – evaluating the
impact of BPH, MED and UI
Boyle P et al. J Epid Biostat 1998; 3: 179–87

The UrEpik Study – evaluating the
impact of BPH, MED and UI
Secondary aims:
 Identify factors predicting medical consultation
 Characterise co-morbid conditions
 Define cultural factors affecting
knowledge/attitudes to urological conditions
 Determine healthcare resources used
 Reassess ability of I-PSS to identify patients
with BPH
Boyle P et al. J Epid Biostat 1998; 3: 179–87

BPH - an increasing problem
Economic burden of BPH

Disfunción Sexual y Prostatismo

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Disfunción Sexual y Prostatismo

Similar to Disfunción Sexual y Prostatismo (20)

More from Uro Woller

More from Uro Woller (20)

Recently uploaded

Recently uploaded (20)

Disfunción Sexual y Prostatismo

Editor's Notes