118 Curing erectile dysfunction — long term effects of taking PDE-5-inhibitors on a daily basis

117 ERECTILE IDENTIFY IMPOTENCE

DYSFUNCTION: ENDOTHELIAL

118

LOOKING FOR A BLOOD TEST TO DISEASE IN PATIENTS CONSULTING FOR

CURING TAKING Sommer

Garcia Cardoso Caceres P.2

J.V.l, Vela Navarrete

R.‘, L6pez

Farre A.*, Garcia Mendez

A.‘,

ERECTILE DYSFUNCTION - LONG TERM PDE-5-INHIBITORS ON A DAILY BASIS F., Engelmann

EFFECTS

U

Mateos

University

IFundacion Jimenez Diaz. Universidad Autonoma, Department of Urology, Madrid, Spain. 2Fundacion Jimenez Diaz. Universidad Autonoma, Department of Urology and Cardiovascular Research, Madrid, Spain

Medical

INTRODUCTION contribute to the cells within the bedtime induced study was aimed function.

& OBJECTIVES: The role of laboratory workup in the evaluation of patients with E.D. is very limited. However, most molecular mechanisms involved in E.D. such as eNOS, sGC, cGMP, are now well known and easily determined. Besides, the presence and content of a cytosolic protein causin, 0 endothelial dysfunction (EDIP) could be simultaneously evaluated. The question to be answered for clinical purposes is the following: could we recognize in patients with E.D. if they are at risk of suffering endothelial disease? A laboratory test answering this question would be highly appreciated by clinicians.

INTRODUCTION

Centre

Cologne,

Department

of Urology,

Cologne,

Germany

& OBJECTIVES: Nocturnal erections occur at all ages and maintenance of the morphodynamic integrity of smooth muscle corpora cavernosa. It has been shown that sildenafil taken at a significant improvement in nocturnal penile erections. This at evaluating the effect of sildenafil taken at bedtime on erectile

MATERIAL & METHODS: In a prospective, randomised, controlled trial to determine whether sildenafil taken at bedtime affected erectile function after one year, 76 patients were randomly assigned to two groups (1st group: 50 mg sildenafil taken every night at bedtime, 2nd group [control group]: 50-100 mg sildenafil on demand). Additionally, a 3rd group was also followed up, consisting of patients who did not undergo any medical therapy. Average patient age was 47.1 years and all patients had experienced erectile dysfunction (ED) for more than 6 months. Sildenafil was taken by groups 1 and 2 for a period of 12 months, followed by a wash-out phase of one and six months respectively. The primary efficacy measures were EF domain score (questions l-5 and 15) on the International Index of Erectile Function (IIEF) questionnaire and peak systolic velocity (PSV) of penile arteries after 12 and 13 months of treatment.

& METHODS: eNOS and sGC (RI-subunit) expression as cGMP generation and EDIP content were determined in mononuclear cells obtained from both Corpora Cavernosa (C.C.) and peripheric vein blood. 16 healthy volunteers were compared with a matched group of 33 E.D. patients, 22 of vascular origin (VED) and 11 of neurological origin (NED). eNOS and sGC expression were determined by Western blotting and EDIP was detected by electrophoretic shift mobility assay (EMSA).

MATERIAL

A similar pattern was observed in mononuclear cells from CC. or peripheric vein blood. A significant reduction in eNOS expression was observed in E.D. patients compared with healthy volunteers (17.02+/- 4%). This eNOS reduction was more important in mononuclear cells of patients with VED compared with patients of NED (79+/-3 vs. 66.5 +i5 arbitrary units). The expression of the Sgc PI-subunit was significantly increased in the mononuclear cells of patients with E.D. (64+/-7 arbitrary units of control group, 253 +/- 9 arbitrary units in VED group and 238.8 +/- 10 arbitrav units in NED). cGMP was significantly reduced in the mononuclear cells of patients with ED. EDIP protein content in the mononuclear cells was increased in patients with E.D., much more in patients with VED ( 81, 65 i 7 vs. 52,4 i 5 arbitrary units), inversely proportional to the eNOS reduction.

RESULTS:

RESULTS: All patients with an IIEF domain score 2 26 were defined as having normal erectile function. After the one-month “wash-out” phase, 58.8 % of Group 1, and 9.7 % of Group 2 had an IIEF domain score 2 26. PSV of the cavernous arteries improved in Group 1 from 29.4 f 9.8 cm/s to 38.9 * 10.3 cm/s (p
Mononuclear cells from peripheral veins of patients with ED contain the same information as the same cells from C.d. blood. Because of its significant increase in E.D. patients, the receptor of NO, the sGC l3l-subunit, was the most sensitive discriminator between healthy volunteers and ED patients. eNOS expression and cGMP content were both significantly reduced in ED patients. However, their reduction was not so pre-eminent as the sGC RI-subunit in its increase. Patients with vascular ED had a significant reduction of eNOS exoression and marked content of EDIP. which was not the caseyn neurological ED patients. ’ The bases for an ED blood test, a test that would be highly appreciated in clinical practice, with potential pathogenic, prognostic and therapeutic implications, have been established. More work is necessary to define its sensitivity and specificity. CONCLUSIONS:

CONCLUSIONS: To our knowledge, this is the only study worldwide that has investigated the long-term effects of taking PDE-5-Inhibitors on a daily basis. After only one year, sildenafil taken regularly at bedtime may be able to bring about regression of ED or can be a useful tool for curing ED.

119 STRATIFICATION BY OUTCOMES VIAGRAB (SILDENAFIL CITRATE) ERECTILE DYSFUNCTION DURING FOLLOWING RADICAL PROSTATECTOMY

OF

120 CARDIOVASCULAR PARAMETERS CHANGES IN PATIENTS WITH ERECTILE DYSFUNCTION USING 5-PDE INHIBITORS: A FIRST STUDY WITH SILDENAFIL 50MG AND VARDENAFIL 1OMG

AFFECTING RESPONSE TO IN THE TREATMENT OF THE FIRST 6 MONTHS

Montorsi F.‘, Snicker P.2,Jaudinot E.?, Wohlhuter C.4, Puppo P.5,Teillac P.h

Pomara G.l, Morelli G.‘, Pox~ara S.2, Taddei S.3, Ghiadoni L.3, Dinelli N.‘; Travaglini M.‘. Mondaini N.4. Salvetti A.3, Selli C.’

lUniversitB Vita e Salute San Rtiaele, Department of Urology, Mdan, Italy, ‘St. Vincent’s Clinic, Department of Urology, Sydney, Australia. jPfizer Inc, Cedex, France, ‘Pfizer Inc, New York, United States,51stitutoNazionale per la Ricerca sul Cancro, Geneva, Italy, OHBpitalSaint-Louis, Department of Urology. Paris, France

‘Piss University, Department of Urology, Pisa, Italy, *Clvico and Benfratelli Hospital, Andrology Unit, Department of Urology, Palermo, Italy, 3Pisa University, Department of Internal Medicine, Piss, Italy, 4Florence University, Department of Urology, Florence, Italy

INTRODUCTION & OBJECTIVES: The goal ofthis study was to assessthe eflicacy of sildenafil m men with erectile dysfunction (ED) after prostatectomy, stratified by age, cardiovascular history. tumour status and Gleason

score, time since surgay. and neurovascular bundle preservation. MATERIAL & METHODS: This was a 12.week, double-bhnd, multicenhe study evaluating the use of flexibledose sildenafil (25, 50, 100mg) or placebo (randomlred 2.1, pm, no more than once daily). Men with normal preoperative exctile function who had undergone radical prosratectomy within 1 to 6 months of the start of the study and experienced ED as a result of surgery were eligible. Primary efficacy parameters mcluded quesrlon 3

(Q3, ability to aclneve an erection) and 44 (ability to maintain an erection) from the lntemat~onalIndex ofErectile Funcnon (IIEF). Q3 and Q4 are scored from 0 (no sexual activity) to 5 (almost always/always). RESULTS: Overall, 281 patients were analyzed for efficacy (placebo, n=96; siidenafd, n=185). Sildaafil was efficacious in improving the ability to achieve (03) and maintain (Q4) an erection m the overall population compared with placebo. Among these patlents, 55% of men were >60 years of age, 23% had a turnour status > T3, and 42% had undergone surgery with no or unilateral bundle preservation. Mean efficacy scores for patient subgroups that are presented in bold, have 95% confidence intervals that do not overlap (table). CONCLUSIONS: While men within 6 months of prostatectomy traddmnally do not respond well to pharmacotherapy.for ED, sildenatil beahnenf improved erectile function in men with ED resulting from radical

prostatectomy. Tha IS the first time that the effects of variables such as tumour status, ‘ype of surgery, and time since surgery on sildenafil efficacy have been assessedm a double-blind placebo-controlled trial.

&;y

Sildenafil

Mean &ore (95% CI) Sildenafil Placebo

560 > 60

1.20(0.9-l S) 1.28(1.0-1.6)

2.14(1.8-2.5) 1.71(1.4-2.0)

1.22(0.9-1.5) 1.17(09-l 4)

1.99(1.7-2.3) 1.71(1.4-2.0)

Days since surgery 590 > 90

l.I7(0.9-1.5) 1.29(1.0-1.5)

1.89(1.6-2.2) 1.91(1.6-2.2)

0.97(0.8-l .I) 1.35(1.0-1.6)

1.74(1.4-2.0) 1.92(1.6-2.2)

Tumour statu ST2

1.32(1.1-1.6)

tT3

1.00(0.8-1.2)

1.96(1.7-2.2) 1.660.3.2.0)

1.22(1.0-1.4) 1.14(0.7-1.6)

1.94(1.7-2.2) 1.43(1.1-1.8)

European

Urology

Supplements

3 (2004)

No. 2, pp. 32

I

F.‘, Dicuio

INTRODUCTION & OBJECTIVES: Sildenafil is nowadays the most prescribed oral agent for patient with erectile dysfunction (ED). Vardenafil is a new inhibitor of PDE type 5 recently approved to treat patients with ED of various causes. Both these PDE-5 inhibitors have vasodilating properties and effects on blood pressure (BP) and, as well as nitrates. they work through the nitric oxide cyclic guanosine monophosphate pathway. The aim of our study was to Investigate the influence of both these PDE-5 inhibitors on blood pxssure and heart rate in normotensive men with ED, by a cross-over comparison. MATERIAL & METHODS: 35 patients with ED were enrolled to evaluate and compare the effect of Sildenafil 5Omg and Vardenatil IOmg on blood pressure and heart rate. At the screening (baseline) visit, sitting systolic, diastolic blood pressure (B-SBP; B-DBP) were measured as well as heart wte (HR). Three dosesmeek (on alternate days) of Sildenafil 50mg were administrated to patients, late in the afternoon and on an empty stomach. Sitting systolic blood pressure (SildSBP), diastolic blood pressure (Sild-DBP) and heart rate (HR) were recorded before dosing, and after 30 min, 60 min; 120 min, and 240 min. After 3.weeks wash-out period patients were crossed over to Vardenafil 10 mg with the same study design. Statistical analysis was performed using ANOVA for repeated measures and Sheffe’s test for multiple comparison testing. Differences were considered statistically significant at a value of p