Ejaculation. Emission. Ejection. Orgasm

Transcription

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2 Ejaculation Emission Ejection Orgasm

3 Ejaculation sc T10-L2 S2-4 Emission: vas deferens, prostate, bladder neck Post. Urethra distention Ejection: Pelvic Floor / bulbocavernous muscle contraction Orgasm: pressure release in post urethra contraction of accessory sex organs

4 Ejaculation Disorder - Early ejaculation - Delayed ejaculation - Anejaculation / reduced ejaculation - Retrograde ejaculation

5 MSAM-7 Multinational Survey of the Aging Male Objective: To evaluate in populations of men aged years: Incidence of LUTS and their severity Importance of sexuality and incidence of sexual disorders Possible relationship between LUTS and sexual disorders, including impact of co-morbidities (diabetes, hypertension) Rosen R et al. Eur Urol 2003; 44:

6 DAN-PSS sex Prevalence of functional problems Erection (reduced / none) 49% Ejaculation (reduction / none) 46% Ejaculation (pain / discomfort) 7% Among total sample (n=12,815) Rosen R et al. Eur Urol 2003; 44:

7 DAN-PSS sex Bothersomeness of functional problems Erection (reduced / none) 78% Ejaculation (reduction / none) 55% Ejaculation (pain / discomfort) 88% Among men with functional problems Rosen R et al. Eur Urol 2003; 44:

8 BPH Therapies: Impact on Ejaculation Watchful Waiting: no effect on ejaculation Surgery 1. TUR-P EjD:25-55%, ED: 13% 2. Minimal invasive surgery pain and discomfort with ejaculation Retrograde ejaculation: 18%

9 Effect of Doxazosin YH Cho, DG Kim, KS Lee. KJU 2004;45(2)

10 AUA Meta-Analysis Ejaculatory Dysfunction Estimated occurrence rate with 95% CI AUA guideline on BPH, J. Urol. 2003; 170,

11 α1-blockers & ejaculatory disorders 20 Tamsulosin (3 months) 18% 20 Alfuzosin OD (3 months) % % Pbo Tam 0.4mg Tam 0.8mg 5 0 0% Pbo 0.6% 0.6% Alf 10mg Alf 15mg Lepor H et al. Urology 1998; 51: ; 900; Roehrborn CG et al. Urology 2001; 58:

12 α1-blockers & ejaculatory disorders Roehrborn et al. BJU Int 2003 Narayan et al. Ur ology 2001 Schulman et al. J Urol 2001 Exposure time 3 months 16 months 4 years n=473 % n=949 % n=515 % Abnormal eja culation Impotence Decreased li bido NA NA 1.2 Alfuzosin 10mg OD Tamsulosin mg 0.8mg Tamsulosin 0.4mg

13 What is the mechanism? sc T10-L2 S2-4 Emission: vas deferens, prostate, bladder neck Post. Urethra distention Ejection: Pelvic Floor / bulbocavernous muscle contraction Orgasm: pressure release in post urethra contraction of accessory sex organs

14 Retrograde Ejaculation?

15 ABEJAC Study Treatment 1 Treatment 2 Treatment 3 10-day Washout 10-day Washout 5-day treatment 5-day treatment 5-day treatment Screening Day 10 /Day 5 Placebo No treatment Tamsulosin 0.8mg OD Alfuzosin 10mg OD Double-blind cross-over study in 57 young healthy volunteers with normal sperm and no retrograde ejaculation Hellstrom,WJG:AUA 2005

16 ABEJAC Study Assessments Ejaculate volume Post-ejaculate sperm concentration in urine Retrograde ejaculation defined by sperm count in urine > 5 millions/ml Hellstrom,WJG:AUA 2005

17 ABEJAC Study Change in ejaculate volume (ml Change in ejaculate volume +0.3 *Tam vs Pbo, p<0.001 Tam vs Alf, p< * 0 Mean ±sd value at baseline 3.4 ± 1.4 ml Mean ±sd value at baseline 48 ± 0.5 million/ml Placebo Alfuzosin 10mg OD Tamsulosin 0.8mg OD Change in urine sperm conc. (million/m Change in urine sperm concentration p=ns Intent to treat population Hellstrom,WJG:AUA 2005

18 ABEJAC Study % with decrease in ejaculate volume >20% Tam vs Alf, p<0.001 Tam vs Pbo, p<0.001 * 90% % 21% 0 Placebo Alf. 10mg OD Tam. 0.8mg OD Among completers (n=48) Hellstrom,WJG:AUA 2005

19 ABEJAC Study Complete anejaculation: Placebo: 0% Alfuzosin 10mg OD: 0% Tamsulosin 0.8mg OD: 17 (35.4%) 2/17 with retrograde ejaculation Hellstrom,WJG:AUA 2005

20 ABEJAC Study Conclusions Nearly all volunteers (90%) receiving tamsulosin 0.8mg had reduced ejaculation and 1 out of 3 had complete anejaculation which was not retrograde ejaculation Further research needed to elucidate mechanisms of ejaculatory dysfunction with tamsulosin

21 Hisasue et al., AUA male healthy urologists Tamsulosin 0.2mg and 0.4 mg administrated in a crossover manner for 3 days Significant decrease in ejaculate volume with tamsulosin: Controls: 3.21±1.17 ml Tamsulosin 0.2 mg: 1.75±1.27 ml Tamsulosin 0.4mg: 1.64±1.60 ml No retrograde ejaculation

22 Ejaculation sc T10-L2 S2-4 Emission: vas deferens, prostate, bladder neck Post. Urethra distention Ejection: Pelvic Floor / bulbocavernous muscle contraction Orgasm: pressure release in post urethra contraction of accessory sex organs

23 The physiology of ejaculation: The emission phase Semen contribution: Seminal vesicle (50 80%) Prostate (15 30%) Cowper s s gland Testis (<0.1%) Emission from the ejaculatory orifice Bladder Emission from the prostate Penis Prostate EUS BCM SV Vas deferens Epi Testis Mann and Lutwak-Mann Male reproductive function and semen Springer-Verlag 1981:

24 Vas deferens & seminal vesicle The α 1 -adrenoceptor subtype involved in contr action of the human vas deferens is most prob ably the α 1a -adrenoceptor 1,2 In vitro studies in rats have shown that the α 1a - adrenoceptor subtype also plays a major role in the contraction of the seminal vesicle (responsi ble for 70% of the amount of ejaculate) 3 1. Furukawa et al. Br J Pharmacol 1995; 116: Moriyama et al. Br J Pharmacol 1997; 122: Silva et al. Eur J Pharmacol 1999; 381:

25 CNS and sexual function Erection: In rats, central α 1 -adrenoceptor stimulation increases sexual function 1 Ejaculation: Stimulation of α 1 -adrenoceptor results in reduction of ejaculation latency. Blockade reverses the condition Predominance of α 1D receptors in the human spinal cord. 2 Stimulation of these α 1 receptors could theoretically mediate facilitation of ejaculation 3 1. Bitan et al. Neurosci Biobehav Rev 1987; 11: Smith et al. Mol Brain Res 1999; 63: , 261, 31st International Consultation on Erectile Dysfunction

26 Central Pattern Generator for Ejaculation & Noradrenergic agents Spinalized rats Carro-Juarez M, IJIR 2006

27 Summary & Conclusion Ejaculatory disorder is common and bothersome Alpha blockers can induce ejaculatory disorder However, mechanism unclear; needs elucidation Quantitative measurement of bother needed for EjD induced by alpha blockers

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