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Calais da Silva F, Marquis P, Deschaseaux P et al. Eur urol, 1997, 31(3) : 272-280.
MSAMMSAM-7
Multinational Survey of the Aging Male
Objective: To evaluate in populations of men aged 5080 years: 50
Incidence of LUTS and their severity Importance of sexuality and incidence of sexual disorders Possible relationship between LUTS and sexual disorders, including impact of coco-morbidities (diabetes, hypertension)
Rosen R et al. Eur Urol 2003; 44: 637649
MSAMMSAM-7
The largest study on sexual impact of LUTS
Materials and methods (1) Patients: More than 14,000 men aged 50 to 80 years in 7 countries (USA, UK, France, Germany, Italy, Spain and The Netherlands) In each country, the sample was representative of the target population
Rosen R et al. Eur Urol 2003; 44: 637649
MSAMMSAM-7
MSAMMSAM-7
The largest study on sexual impact of LUTS
Materials and methods (3) 34,800 questionnaires sent 14,254 questionnaires returned 12,815 questionnaires evaluable & analysed (89.9%)
100 90 80 70 60 50 40 30 20 10 0
Total
5059 50
60 6069
7080 70
Age
Rosen R et al. Eur Urol 2003; 44: 637649 / Data on file
Total
5059 50
60 6069
7080 70
Age
Rosen R et al. Eur Urol 2003; 44: 637649
DAN-PSS sex
Prevalence of functional problems
49%
46%
7%
Among total sample (n=12,815)
DAN-PSS sex
Bothersomeness of functional problems
78%
55%
88%
8 6 4 2 0
4.9
US
FR
DE 50-59 y.
IT 60-69 y.
NL 70-80 y.
SP
UK
100
Impotence
90 80 70 60 50 40 30 20 10 0
OPEN
Retrograde ejaculation
TURP TUIP
TUMT
ILC
TUNA
What is the Impact of Medical Therapies? Are there Differences Between Medical Therapies?
5E-Reductase
Impotence Double-Blind Placebo-Controlled Studies
VA study
(Lepor et al)
PROWESS
(Marberger et al)
PLESS study
(McConnell et al)
2 yrs Placebo n=1,591 % 5.0 9.0 NA 2.0 2.8 4.7 NA 0.6 4.0 6.6 NA 2.1 3.4 3.7 0.8 0.1 Fina n=1,577
Sexual Function
Direct Comparative Studies (E1Blocker/Finasteride)
10
VA: 1 Year
10
ALFIN: 6 months
p=0.04
% 5
Ejaculatory Abnormality
p<0.001
% 5
0 10
0 10
p=0.05
Decreased Libido
ns
% 5
0 10
0 10
p=0.05
p<0.002
% 5
Impotence
Pbo
Lepor H et al. NEJM 1996;335:533 Debruyne FMJ et al. Eur Urol 1998;34:169
T+F
E1-Blockers
Impotence Double-Blind Placebo-Controlled Studies
n=143 0% 0% 0%
n=150 0% 0% 0.7%
E1-Blockers
Ejaculatory Disorders US Pivotal Studies with Tamsulosin
Alfuzosin
Tamsulosin (3 months) Abnormal ejaculation (%) 20 15 10 5 0
6%
Alfuzosin OD (3 months)
18%
*p < 0.001
20 15
ns
10 5
0% 0.6%
0%
0.6%
Pbo
Tam 0.4 mg
Tam 0.8 mg
Pbo
Alf 10 mg
Alf 15 mg
E1-Blockers
Ejaculatory Disorders Long-Term Studies with Tamsulosin
Alfuzosin
US open study with tamsulosin 0.4-0.8 mg OD * 0.4Mean exposure time: 16 months Tamsulosin European open study with tamsulosin 0.4 mg OD ** Mean exposure time: 4 years Tamsulosin
30%
4.9%
European open study with alfuzosin 10 mg OD *** Mean exposure time: 9 months Alfuzosin
0.6%
*Narayan P. et al. Urology 1998 **Schulman C. et al J Urol 2001 ***Van Kerrebroeck et al. Eur Urol. 2000
E1-Blockers
Ejaculatory Disorders Long-Term Studies with Tamsulosin
Alfuzosin
van Kerrebroeck et al. Eur Urol 2002 Exposure time Abnormal Ejaculation Impotence Decreased Libido 12 months % 0.6 1.4 0.3 Alfuzosin 10 mg Narayan et al. Urology 2001 16 months % 30 6 NA Tamsulosin 0.4-0.8 mg Schulman et al. J Urol 2001 4 years % 4.9 5.4 1.2 Tamsulosin 0.4 mg
DAN-PSSsex
Reduced Ejaculate, a Problem
In % 100 90 80 71 70 60 50 40 30 20 10 0 39 54 44 66 54 66 85 80 76
52
50
LUTS
50 - 59 years 60 - 69 years 70 - 79 years
2.6
2.3 * 1.5
Reduced erection
Reduced ejaculate
Painful ejaculate
DAN-PSSsex -
Anxiety
Deterioration in Self-Image
ABEJAC Study
Materials and Methods Using a randomized, 3-way crossover design, the effects of 5 days of treatment with 0.8 mg tamsulosin daily, 10 mg alfuzosin daily and placebo on ejaculation in healthy adult men were compared. The primary end points of the study were ejaculate volume and sperm concentration in post-ejaculate urine on each treatment. The healthy volunteers who completed the study were 48.
J Urol. 2006 Oct;176(4 Pt 1):1529-33.
ABEJAC Results
Change in ejaculate volume
Change in ejaculate volume (ml)
3 2 1 0 -1 -2 *Tam vs Pbo, p<0.001 Tam vs Alfu, p<0.001
+0.4
+0.3
-2.4
-3
Mean
* sd value at baseline
3.4 1.4 ml Placebo Alfuzosin 10mg OD
ABEJAC Results
% with decreased ejaculate volume >20%
90%
100 *Tam vs Pbo, p<0.001 Tam vs Alfu, p<0.001 80
% of subjects
% of subjects
60 40 20 0
60
35%
40
21%
20
13%
0%
0%
Placebo
J Urol. 2006 Oct;176(4 Pt 1):1529-33.
Alfuzosin 10mg OD
Tamsulosin 0.8 mg OD
ABEJAC Conclusions
Nearly all volunteers (90%) receiving tamsulosin 0.8mg had a significant reduction in ejaculate volume and 1 out of 3 had no ejaculation. This reduced ejaculation with tamsulosin is not due to retrograde ejaculation.
Conversely, with alfuzosin 10mg once daily, the percentage of subjects with reduced ejaculation is similar to placebo.
1Giuliano
et al. BJU Int. 2004 : 93:605-8 et al. J.Pharmacol. Exp. Therap. 2005 3Giuliano et al. EAU 2005 (abstract 141)
2Tambaroa
ABEJAC Conclusions
The mechanism by which tamsulosin impairs ejaculation may be a peripheral effect on seminal vesicles and/or on vas deferens1-2. A central effect is also plausible as tamsulosin shows an important affinity for 5HT1A and D2-like receptors that are both involved in the central control of ejaculation3.
1Giuliano
et al. BJU Int. 2004 : 93:605-8 et al. J.Pharmacol. Exp. Therap. 2005 3Giuliano et al. EAU 2005 (abstract 141)
2Tambaroa
Short-Term, Randomized, Double-Blind, Placebo-Controlled, Crossover Study. Sperm parameters were evaluated in healthy men receiving tamsulosin, alfuzosin, and placebo
Study design
48 healthy men received 5 days of tamsulosin 0.8 mg once daily (QD), alfuzosin 10 mg QD, and placebo in a randomized, double-blind, 3-way crossover study with a 10-14-day washout period between treatments.
The mean (SE) changes from baseline in semen sperm concentration, semen sperm count, semen viscosity, semen fructose, sperm motility, and sperm morphology on Day 5 of treatment.
Results
The total sperm count in semen decreased from baseline with tamsulosin -54.6 (24.0) million] but not with placebo [81.5 (18.8) million] or alfuzosin [46.2 (19.0) million]. The percentage of men with normal semen viscosity was lower with tamsulosin (65%) than with placebo (98%) or alfuzosin (92%). The change from baseline in semen sperm concentration was 3.1 (8.3) million/mL with tamsulosin, 15.0 (6.5) million/mL with alfuzosin, and 24.4 (6.5) million/mL with placebo.
Published-Ahead-of-Print on February 5, 2009 by Journal of Andrology
Results
The change from baseline in semen fructose was comparable for all treatments. The percentage of motile sperm decreased 13.8% from baseline to Day 5 of treatment with tamsulosin compared with decreases of 2.3% with placebo and 0.4% with alfuzosin. The percentage of abnormal sperm increased marginally with tamsulosin (0.6%) but not with placebo (-2.8%) or alfuzosin (-3.9%).
Published-Ahead-of-Print on February 5, 2009 by Journal of Andrology
Safety results
The most common adverse events were
dizziness
(alfuzosin 11%, tamsulosin 14%, placebo 0%)
orthostatic hypotension
(alfuzosin 25%, tamsulosin 11%, placebo 5%).
Conclusion
The results suggest that tamsulosin has a negative impact on sperm in healthy men. Studies on the effects of alpha1adrenergic blockers on sperm in men with BPH are warranted.
Hendry et al. in Erectile Dysfunction. Jardin et al. (eds), Health Publication Ltd, Plymouth, 1999:477-50.
)nim( EMIT
021001 08 06 04 02 0 02- 04- 06- 080
.v.i ,gk/gm 4.0 .v.i ,gk/gm 1.0 .v.i ,gk/gm 30.0
nisozareT
nisozarP
nisozuflA
120
*p <0.001
80
*
40
0 Vehicle 3 10 3 10
Tamsulosin ( g/kg)
F. Giuliano et al. , ISSIR 2002
Alfuzosin ( g/kg)
K.-E. Andersson