Transcript PowerPoint 簡報

Men’s Health
The Urological Outlook
Dr Andrew Yip
Consultant Urologist
Chief of Service
Kwong Wah Hospital
Hong Kong
7 November 2010
Male Urological Diseases
1.
2.
3.
4.
Benign prostatic hyperplasia
Prostate cancer
Erectile dysfunction
Premature ejaculation
Prostatic problems
↑number of patients
1.
2.
3.
Ageing population
↑public awareness
Effective medical treatments
Hong Kong


Public urologic service
Non-emergency cases waiting time for
first consultation
18-24 months
Prostate Disease
Prostatitis 2%
Prostatic cancer
18%
BPH 80%
BPH is the most prevalent disease
to affect men beyond middle age
45
40
35
30
25
(%)
Age (years)
20
15
10
5
0
40-49
50-59
60
Three fundamental features of
Benign Prostatic Hyperplasia
Hyperplasia
Symptoms
Obstruction
Large prostate ≠obstruction
* clinical symptoms *
The prevalence of anatomical benign prostatic hyperplasia rises with age. By the
age of 90 years, the disease is virtually universal in men.
Data from the Baltimore Longitudinal Study of Aging Suggest that the prevalence of
symptomatic benign hyperplasia also increases progressively with age.
Decrease in maximum urinary flow rates over 3 years for different age groups
detected in men from Olmstead County
The symptoms of BPH may remain
unchanged or deteriorate only slowly
over time
Improved with time: 15%
Worsening symptoms: 55%
Remain stable: 30%
Cumulative incidence of acute urinary retention over 6 years. The risks of
this complication of benign prostatic hyperplasia rise progressively with age
Differential diagnosis of lower
urinary tract symptoms

Neurological conditions
– Parkinson’s disease
– Cerebrovascular
accident
– Multiple system atrophy
( Shy-Drager syndrome)
– Cerebral atrophy
– Multiple sclerosis

Neoplastic disorders
– Prostatic cancer
– Carcinoma in situ of the
bladder

Inflammatory disorders
– Urinary tract
infection/bladder stone
– Interstitial cystitis
– Tuberculous cystitis

Other causes of
obstruction
– Bladder neck
dyssynergia
– External sphincter
dyssynergia
– Urethral stricture
Management


watchful waiting
medical therapy
– α blocker
– Finasteride
– phytotherapy

surgical therapy
Phytotherapy
About 30 different compounds base on seven major plant extracts:
American Dwarf Palm/Saw Palmetto
Fruits
Serenoa Repens / Sabal Serrulata
African Plum tree
Barks
Pygeum Africanum
South African Star Grass, Pine,
Spruce
Roots
Hypaxis Rooperi, Pinus, Picea
Stinging nettle
Roots
Urtion Dioica
Pye
Pollen
Secale Cereale
Pumpkin
Seeds
Cucurbita Pepo
Cactus flower extracts
Flower Opuntia
•
Their mechanism of action is often unclear
•
Most were introduced into the market without firm proof of efficacy
•
They were not recommended by the WHO committees as appropriate
treatment: although there is uniformity in the results of several meta-analyses
to suggest clinical efficacy for these compounds, it was the opinion of the
committee that the claim or the extent to which the various phytotherapies
are beneficial in the management of BPH/LUTS cannot be confirmed
conclusively without large, appropriately randomized clinical trials of adequate
duration.
Proceedings of the 5th International Consultation on BPH, 1998
Prostate Cancer
Lifetime Probability of Developing Cancer, by Site, Men,
2000-2002*
Site
All sites†
Prostate
Risk
1 in 2
1 in 6
Lung and bronchus
1 in 13
Colon and rectum
1 in 17
Urinary bladder‡
1 in 28
Non-Hodgkin lymphoma
1 in 46
Melanoma
1 in 52
Kidney
1 in 64
Leukemia
1 in 67
Oral Cavity
1 in 73
Stomach
1 in 82
* For those free of cancer at beginning of age interval. Based on cancer cases diagnosed during 2000 to 2002.
‡ Includes invasive and in situ cancer cases
Source: DevCan: Probability of Developing or Dying of Cancer Software, Version 6.0 Statistical Research and
Applications Branch, NCI, 2005. http://srab.cancer.gov/devcan
Cancer Incidence Rates* for Men, 1975-2002
Rate Per 100,000
250
Prostate
200
150
Lung
100
Colon and rectum
50
Urinary bladder
Non-Hodgkin lymphoma
Melanoma of the skin
0
1975
1978
1981
1984
1987
1990
1993
1996
1999
2002
*Age-adjusted to the 2000 US standard population.
Source: Surveillance, Epidemiology, and End Results Program, 1975-2002, Division of Cancer Control and
Population Sciences, National Cancer Institute, 2005.
Prostate Cancer Trends in Incidence and
Mortality, 1973–1999
Note Influence of PSA Assay
250
Incidence
Mortality
200
150
100
50
0
1973 1975 1977 1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999
Year
Prostate Cancer Incidence Rates by
Stage
120
100
Rate per 100,000
Localized
80
60
Regional
40
Distant
Unstaged
20
0
1973 1975 1977 1979 1981 1983 1985 1987 1989 1991 1993 1995
Year of Diagnosis
Prostate Cancer Risk factors:

Increased risk
Family history
– 10% CaP genetic
– Multiple DNA Loci being
examined



High fat diet
African-American race
Increasing age
Multiple Risk Factors
Amplify Risk




Decreased risk
Low fat diet
Lycopene
Vit E, Selenium
Finasteride (Proscar)
– Decreased total
incidence
– Increased high grade
disease
Prostate Cancers Vary in Their Natural Histories
Death From Prostate Cancer
Patient 1
Symptomatic Phase
Progression of Disease
Patient 3
Patient 2
Detectable
Death fromPresymptomatic
Other Causes Death from Other Causes
Phase
Patient 4
Disease Not
Detectable
Remaining Expected Lifetime
Challenges of prostate cancer
screening and treatment




Goal: Find clinically significant cancer at a
point when a cure is possible
Goal: Avoid excessively aggressive
treatment in clinically insignificant disease
Examine prognostic factors of diagnosed
disease to predict if it will be significant
Consider patient medical issues, age,
philosophy
Prostate Cancer: Not to be confused with Benign
Prostatic Hypertropy (BPH)




BPH is age related enlargement of benign tissue
Enlarged tissue can cause urinary symptoms
Treatment initiated if symptoms are bothersome,
infections or incomplete bladder emptying
In contrast, Prostate cancer in early stages has no
symptoms
Diagnostic triad for early detection of prostate cancer
Screening Guidelines for the Early Detection of
Prostate Cancer
American Cancer Society



The prostate-specific antigen (PSA) test and the digital rectal examination
(DRE) should be offered annually, beginning at age 50, to men who have a
life expectancy of at least 10 years.
Men at high risk (African-American men and men with a strong family history
of one or more first-degree relatives diagnosed with prostate cancer at an
early age) should begin testing at age 45. Starting at age 40 can be
considered.
For men at average risk and high risk, information should be provided about
what is known and what is uncertain about the benefits and limitations of
early detection and treatment of prostate cancer so that they can make an
informed decision about testing.
Features of prostate-specific
antigen






glycoprotein whose function is to liquify
semen
produced exclusively by prostatic epithelium
normal serum value less than 4 ng/ml
elevated in 25% of patients with BPH
increased in most cases of prostate cancer
tends to rise progressively with age and
prostatic volume
Interpretation of prostatespecific antigen (PSA) values
PSA value
 < 4 ng/ml
 4-10 ng/ml
 > 10 ng/ml
Interpretation
 8% cancer
 20-25% cancer
 >50% cancer
Recommended age-adjusted
PSA cut-off values
Age (years)




40
50
60
70
-
49
59
69
79
PSA cut off value
(ng/ml)
 2.5
 3.5
 4.5
 6.5
Prostate Specific Antigen
(PSA)




Prostate specific, not cancer specific.
Lacks sensitivity and specificity.
Elevated in BPH, infection.
25% of men with prostate cancer have
PSA < 4.0.
Digital Rectal Exam




Poorly reproducible
Lacks sensitivity and specificity.
25% of men with an abnormal DRE
and a PSA < 4.0 have prostate cancer.
50% of DRE-detected prostate cancer
is non-organ confined.
Prostate Cancer
Screening



Serial PSA measurements.
Serial DRE.
Not enough to do one without the
other.
SCREENING
RECOMMENDATIONS
Screen any man > 50 years old with a 10
year life expectancy.
• Screen any man > 40 years old if:
African-American
Positive family history.
• Stop screening when life expectancy is <10
years.
•
Traditional indication for
Prostate Biopsy:
Usually with LE >10yrs



Abnormal DRE regardless of PSA
Abnormal PSA velocity (.75 ng/dL/yr)
PSA > 4.0 or age appropriate range
– Consider decreasing in men in 40’s, 50’s or
with risk factors (FH/AAmerican)

Office procedure, LA, ultrasonic guidance
Elevated PSA does not mean prostate cancer
Unsettled issue
Potential
Benefits
Potential
Harms
• PSA screening detects
cancers earlier.
• Screening is sensitive but
• Treating PSA-detected
cancers may be effective but
we are uncertain which need
to be treated.
not specific
• Overdiagnosis is a problem
but we are uncertain about
the magnitude.
• PSA may contribute to the
declining death rate but we
are uncertain.
• Treatment-related side
effects are fairly common.
In a high risk population this is more clear.
There is little dispute that increasing awareness and
screening in high risk populations is appropriate.
Male Sexual Dysfunction
1.
2.
3.
4.
5.
Erectile dysfunction
Premature ejaculation
Delayed ejaculation
Retrograde ejaculation
Hypoactive sexual desire
Erectile Dysfunction (ED)


A Common disease
High prevalence
MMAS
40-70
52%
Carson C C et al
>40
22% (sometimes or never)
Feldman HA et al
J Urol 1994; 151:54-61
Carson CC et al
J Urol 2002; 167(suppl):29-30
ED Is Prevalent and Increases with
Age: Cologne Male Survey
Age Range (y)
ED (%)
30-39
2
40-49
10
50-59
16
60-69
34
70-80
53
Braun M et al. Int J Impot Res. 2000;12:305-311.
Massachusetts Male Aging Study (US):
Under-treatment of ED
n=639 (45 years of age)
10%
Seek or receive
treatment
90%
Never seek care
McKinlay JB. Int J Impot Res. 2000;12(suppl 4):S6-S11. Based on data from the Massachusetts Male Aging
Study (MMAS). Source: AARP Modern Maturity. Sexuality Study. Washington DC, 1999.
Belgium Observational
Study



1492 ED patients
25% ED>3 years
74% were untreated
Claes H et al Int J Impot Res 2008; 20:418-424
ED is still a taboo topic


Loss of manhood
Loss of self-esteem
ED Treatment


Patients – reluctant to seek treatment
Physicians – uncomfortable to discuss
under diagnosis
under treatment
Why Diagnosing ED Is Important


ED screening may signal underlying disease:
–
–
–
–
Diabetes
Hypertension
Dyslipidemia and coronary artery disease (CAD)
Depression
–
–
–
–
Anxiety
Decreased self-esteem
Reduced quality of life (QOL)
Negative effect on relationships
ED can result in:
Goldstein I. Am J Cardiol. 2000;86(suppl):41F-45F.
Goldstein I. Int J Impot Res. 2000;12(suppl 4):S147-S151.
Francis ME., et al. J Urol. 2007;178:591-596.
Selvin E., et al. Am J Med. 2007;120:151-157.
Jackson G., et al. J Sex Med. 2006;3:28-36.
ED: A First Sign of Cardiovascular (CV) Disease?


In a study of 30 men with ED (International Index of Erectile
Dysfunction-Erectile Function domain [IIEF EF] =13.7±1.2, mean
age, 46.2 years) and 27 age-matched normal men (IIEF EF
domain=21.3±1.2; mean age, 46.6 years) with no history of CV
disease or CV risk factors
Compared with normal men, men with ED had:
– Objective evidence of clinical and penile vascular disease
(mean penile peak systolic velocity=28±3 m/s)
– Reduced brachial artery flow-mediated vasodilation (p=0.014)
– Impaired maximal response to nitrates, 13±1.4% vs. 17.8±1.4%
(p=0.02)
– Improved ED with phosphodiesterase type 5 (PDE5) inhibitor
treatment, mean change in IIEF-EF domain score=3
Kaiser DR et al. JACC. 2004;43:179-184.
Danger of Over-the Counter
‘Natural’ or ‘Herbal’ Products
30% patients
Over-the Counter
Sexual Enhancement Products (Illegal)
Hypoglycaemia
Sidenafil & Glibenclamide
Mainland China
Friends
Local pharmacies
Peddlers
unknown
Hong Kong Med J 2009, 15:196200
Over-the Counter
Sexual Enhancement Products (Illegal)
3 died
1 vegatative state
1 cognitive impairment
7 different kinds of products
- Sidenafil
64 (0.05-198)mg
- Glibenclamide 70 (0-158)mg
Over-the Counter
Sexual Enhancement Products (Illegal)
Singapore – similar experience
3 patients died
Over-the Counter
Analogues of ED drugs
Power 58 轟天炮
Jolex 壯力仕
温養 ONYO 錠劑
勃樂
天力
ete ete
Acetildenafil
Piperidenafil
Acetildenafil
Piperidenafil
Hydroxyhomosildenafil
Hydroxyacetildenafil
Treatment of ED & Hardness
problem
First line therapy
Oral medication – PDE5 inhibitors
Sidenafil (Viagra)
Vardenafil (Levitra)
Tadalafil (Cialis)
How to use PDE5 inhibitor correctly?
1.
2.
3.
4.
5.
6.
1 hour before sex
(usually effect by 30 mins)
Empty stomach
(2 hours after meal)
Require sexual stimulation
No nitrate therapy – heart disease
stroke
Maximum – one dose per day
(in Hong Kong, once per week)
No tolerance phenomenon
Patients
can take
if stable
4-8 doses may be required
to maximize the individual’s response
Premature Ejaculation (PE)
1. What is the definition?
2. What is normal intercourse time?
3. What is the cause?
4. How common?
5. Any consequence?
6. What treatment method?
Is time important?
Intercourse Time (IELT)
Normal population
Waldenger et al
Median 5.4 minutes
Patrick et al
Median 7.3 minutes
Corty & Guardiani
Median 7-13
minutes
PE patients
Waldenger et al
90% within 60 sec
McMahon et al
Median 30 sec
Mean 43.5 sec
Severe PE cases
•
20% of patients
•
Ejaculation – during foreplay
on attempt to penetrate
on putting on condom
begin after penetration
Three controls necessary to define PE:
1. IELT
2. Lack of voluntary control
3. Negative personal consequence
Many respondents had been
experiencing PE for a long time
How long have you experienced PE? (n=423)
40
35
Proportion of respondents (%)
30
25
20
34
15
21
10
15
5
12
6
0
0
Less than a
month
5
2
1- 3 months
4-6 months
6 months- 1
year
2 years
Number of patients
3 years
4 years
4
5 years
> 5 years
Janssen-Cilag, Australia, 2008
Life-long PE
International Society of Sexual Medicine
2008 (Evidence –based definition)
1. Ejaculation which always or nearly always occurs
priors to or within about 1 min of vaginal
penetration; &
2. Inability to delay ejaculation on all or nearly all
vaginal penetrations; &
3. Negative personal consequences, such as distress,
bother, frustration and/or the avoidance of sexual
intimacy
McMahon et al
J Sex Med 2008; 5: 1590-1606
Hypotheses of PE
Adapted from Perelman, Atlas of Male Sexual Dysfunction, 2004
Different types of PE may have different etiology
Misconceptions in Local Patients
1. Too frequent masturbations
2. Too frequent nocturnal emissions
3. Premarital sex
4. Too much cold foods
Serotonin & PE
• Presence of low synaptic levels of
serotonin in regions of the CNS that
modulates ejaculation
• Variations in 5-HT receptor sensitivity
serotonin → delay ejaculation
How common is PE?
What is the prevalence?
Prevalence of PE is similar across countries
PEPA Study
PEPA: Premature ejaculation perceptions and attitudes
Porst et al. (2007) Eur Urol 51:816–824
Prevalence of PE is consistent across age groups
PEPA Study
Porst et al. (2007) Eur Urol 51:816–824
PEPA: Premature ejaculation perceptions and attitudes
Most respondents had not sought help
Have you spoken to or consulted a healthcare professional about PE? (n=423)
No
82%
Yes
18%
Janssen-Cilag, Australia, 2008
With embarrassment being the main barrier
stopping them from doing so
What would you say is the MAIN reason why you have not sought help so far? (n=348)
60
% respondents who have not sought help
50
40
30
20
10
0
Premature ejaculation is
not a problem that can
be helped, I'm just not
good at sex
I don't believe it is a
physical condition
Don't know where to
go/who to ask
It's not a big problem, I
can manage it myself
Too embarrassed
Don't feel anything can
be done
Janssen-Cilag, Australia, 2008
Folklore Methods
1. Cold shower
2. Scrotal traction
3. Special positions during sex
4. Alcohol
5. Recreational drugs
Current PE Treatment Options
1. Self-help treatment
2. Behavioural therapy
3. Topical treatment ( local anaesthetics)
4. PDE5 inhibitors
5. SSRIs
6. PE specific SSRI – Dapoxetine
7. Other not recommended
Selective Serotonin Re-uptake Inhibitors
(SSRIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
increase serotonin levels in the synaptic cleft
Serotonin neurotransmission
is locally regulated by the serotonin
transporter (5-HTT) re-uptake
system
 As serotonin is released,
the transporter system is activated,
removing serotonin from the
synaptic cleft and preventing
over-stimulation of postsynaptic
serotonin receptors
 SSRIs inhibit the serotonin
transporter system, increasing levels
of serotonin in the synaptic cleft and
delay ejaculation

Axon
Axonal
Terminal
5-HTT
5-HTT
5-HT
5-HT
5-HTT
5-HTT
5-HT
Post-Synaptic Neuron
Synaptic
Cleft
5-HTT = serotonin transporter system
5-HT = serotonin
Giuliano (2007) Trends Neurosci. 30(2):79–84;
Adapted from McMahon et al (2004) Disorders of orgasm and ejaculation in men. In Sexual Medicine: Sexual dysfunctions in
men and women. 2nd International Consultation on Sexual Dysfunctions, Paris
Dapoxetine (Priligy)
First oral agent approval for PE
New short-acting SSRI
Conclusion
• PE is the most common male
sexual dysfunction
20% prevalence rate
• Negative impact on sexual satisfaction &
couple relationship
•Great distress to sufferers
•Poor rates of treatment seeking
•A neglected area of male sexual health
•Unmet therapeutic need filled by Dapoxetine