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Dr. Anmar Nassir, FRCS(C) Fellowship in Andrology (U of Ottawa) Fellowship in EndoUrology and Laparoscopy (McMaster Univ) Chairman, Department of Surgery Umm Al-Qura Univ Consultant Urology, King Faisal Specialist Hospital, Jeddah. Introduction.
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Dr. Anmar Nassir, FRCS(C) Fellowship in Andrology (U of Ottawa) Fellowship in EndoUrology and Laparoscopy (McMaster Univ) Chairman, Department of Surgery Umm Al-Qura Univ Consultant Urology, King Faisal Specialist Hospital, Jeddah
Introduction • Chronic renal failure causes a wide-ranging disturbance in men including sexual dysfunction. • Historically, the prevalence of ED among renal failure patients varied : 40 to 90% • Many recent studies reported similar prevalence (80-86%) of sexual dysfunction in male patients while on HD. • Levy 1972, Abram 1975 • Ali 2005, Rosas 2003, Neto 2002, Neya 2002, Aeslan 2002, Rosas 2001, Rosas 2000
This wide range perhaps because of different questionnaires used in addition to variable sample size • Not all studies followed the accurate definition of ED as a persistent inability to achieve or maintain an erection sufficient to permit satisfactory sexual performance. • Ali 2005
There is not enough data about the effect of modern dialysis therapy on sexual function. • data is controversial about whether dialysis is helpful or harmful.
Retrospectively, most studies documented no relationship between the duration of dialysis and severity of ED. • One study demonstrated a significant correlation between the duration of dialysis and the presence of ED among HD patients. • Mehrsai 2006, Soykan 2005, Miyata 2005, Rosas 2003, Neto 2002, naya 2002, Cerqueira 2002, Arslan 2002, Toorian 1997, Steele 1996, Rodger 1984 • Ali 2005
Prospectively, a study on 25 male patient given a sexual questionnaire twice in a period of 6 month to examine the ongoing effect of dialysis on ED and observed no significant improvement. • Criticism : • This study only looked at a subset of a small number mixed of both genders. • They did not assess the patients on entry to dialysis, but randomly at any time between 12–192 months of HD, with a mean of 67 +/- 46.4 months. • Soycan 2005
In other words: • Many previous studies failed to adopt standard criteria to define impotence or to subcategorize sexual dysfunction. • Absence of longitudinal studies planned to evaluate the impact of various renal failure therapies on ED.
Objectives • To determine the prevalence of sexual dysfunction in patients treated for renal failure. • To identify the contributory risk factors. • To determine the effect of standard renal failure treatment on sexual function, while on dialysis or post transplant.
Materials & Methods • Prospective study • Started in 1998 with a follow up divided in stages. • On admission to dialysis • Every 10-12 months • while on dialysis • or post kidney transplantation.
Materials & Methods • The questionnaire used: • The international index of erectile function (IIEF) • with its 5 domains, • used to develop a semiquantitative baseline score useful in follow up. • Other questions • specially designed for our objectives were added.
Results • Population: • 52 pts (at NS, Canada) fulfilled the criteria and returned 149 Questionnaire. • 52 filled 1 questionnaire, • 45 filled 2 questionnaires • 34 filled 3 questionnaires • 15 filled 4 questionnaires • 4 filled 5 questionnaires • Mean age was 58.5 +/- 14.3 (SD)
Results • Renal Failure Therapy: • 25 HD + 27 PD. • During f/u 16 pts received a Kidney Transplant. • F/U ranges from 0 to 48 months (average =20.5) • 14 patients died during f/u. • The rest had a mean f/u of 26 months.
Erectile Function • On entry to dialysis: • 82.7 % have ED • Only 17.3 % were potent • Severity
Kidney Transplantation • Some authors claimed that prevalence of ED in transplanted men was not significantly lower than in dialysis patients. • Better designed studies, based on the IIEF-5 scores of 64 patients: • 78.1% improved, • 12.5% experienced no change • 9.4% had a lower score. • Toorians 1997 • Mehrsai 2006
Kidney Transplantation • In a cross sectional study on 243 transplanted patients, • ED was found in 54.9%. • Factors independently associated with ED were: • age, time on dialysis prior to transplant, and peripheral arteriopathy . • Our data supported the beneficial effect of transplantation on sexual function with an advantage continued in a chronological prospect. • Unmeasured variations in the previous studies probably resulted in the differences. • Rebollo 2003
Evaluation • H & P • IIEF-5 • Ix: • Lab: CBC, Hb1ac, cholesterol, prolactin, Testosterone
66.6 % of ED pt are welling to have it treated. • Only 12 % of ED pt had trt for it. • Half of them received it at >30 months of f/u
Although it is a major factor affecting quality of life in end stage renal disease (ESRD), SD in dialysis patients receives very limited attention by the medical team. • Despite its importance, only 25% of patients discuss sexual function with their physicians • Diemont 2000 • Soykan 2005
Treatment • The reason for not seeking medical help is probably related to the high prevalence of psychological depression. • This high prevalence is well documented. • Peng 2007, Kimmel 2000
Treatment – why not ? • There was significant correlation between the total score of IIEF and • daily activities, • social activities, • social support , • quality of life. • Some patients without sexual activity didn’t perceive their deficiency as a problem and considered this situation inherent to the ageing process . • Martín-Díaz 2006
Treatment • Among different modalities treating ED in ESRD patients, the simplest is using oral medication. • Most studied were done on Sildenafil.
Treatment by Sildenafil • It is recommended to be used on days off dialysis. • Next day after HD has better efficacy. • Some authors showed that ED in two-thirds of HD patients can improve by sildenafil. Yenicerioglu 2002
Treatment using Sildenafil Yenicerioglu 2002
Treatment using Sildenafil Yenicerioglu 2002
Treatment using Sildenafil ROC = (receiver operating characteristic) Yenicerioglu 2002 The ROC curve of the erectile function domain score before treatment for predicting the outcome of sildenafil treatment in patients with ESRD (area under the curve, 0.790)
Treatment using Sildenafil • For the erectile function domain the ROC curve • patients with a score of ≥ 17 seem to respond better to sildenafil treatment • (with a sensitivity of 71% and a specificity of 67%). Yenicerioglu 2002
The response rate was 80% in those using HD when advised to take pills only on days with no dialysis; • Some authors reported transient hypotension after a 50-mg dose of sildenafilin patient on HD • patients may remain relatively hypovolaemic for some time after dialysis, they recommended that sildenafil should be used on days with no dialysis. Mohamed et al. 2002
Treatment using Sildenafil Recommendation: • All patients were started on a 25-mg dose, • Increased to 50 mg if there was no response after two trials. Yenicerioglu 2002
Double-blind, randomized, placebo-controlled study • 50 mg sildenafil • Inclusion: • patients with ED. • Patients on HD for at least 6 mo • With stable relationship with a female sexual partner SEIBEL et al, 2002
Exclusion: • Patients older than 70 yr • penile anatomic abnormalities, • cirrhosis, • diabetes, • angina, • severe anemia, • on nitrate treatment • recent history of stroke or MI . SEIBEL et al, 2002
Treatment • When subdivided, diabetic patients responded less (37.5%) compared to non diabetics (83.3%). Hyodo 2004
Side effects - Sildenafil • At least one side effect was seen in 17/40 patients (43%); • 5/40 (13%) pts reported more than one side-effect • 1 pt severe hypotension in the PD group. • 12 pt (30%) flushing. • 7 pts (18%) mild headache • 1 pt blurred vision Yenicerioglu 2002
Salvage Treatment • 12 patients (8 Tx- & 4 HD) who complained of ED with hypogonadism and cavernosal insufficiency. • Before treatment • all patients had severe ED with a poor IIEF score • 11 had diminished libido. • 11 pts had diminished testicular volume • 6 had elevated FSH Chatterjee 2004
Salvage Treatment • Received • 250 mg IM/m testosterone cypionate and 50–100 mg sildenafil orally once or twice / w • 12 mo • All patients had a good response Chatterjee 2004
Sildenafil in Kidney Tx • Even after renal transplant, those patients who still suffer from ED Sildenafil can be effective in 60%. • Multictr phase IV • 50 pt post Tx w ED • Sildenafil: 50 mg then inc or dec • X 3 mo Castro 2001 • Barrou 2003
Sildenafil in Kidney Tx • 65 ED patients with normal graft function for 3-12 months after kidney Tx were involved in our study. • Erectile dysfunction was diagnosed in all the patients by the IIEF. • Among them, • 10 patients were in light degree; • 32 patients in moderate degree, • 23 patients in severe degree according to IIEF score. Zhang et al, 2005
Sildenafil in Kidney Tx • In each patient, the IIEF score, were compared before and after taking sildenafil citrate at an initial dose of 50 mg every night. Zhang et al, 2005
Sildenafil in Kidney Tx Results • 26 patients without ED before transplantation suffered ED after the operation, • 32 patients with ED before transplantation noticed worsening. • Taking sildenafil citrate was effective in 53 patients (81.54%). Zhang et al, 2005
Sildenafil in Kidney Tx Zhang et al, 2005
Sildenafil in Kidney Tx • Barrou 2003
Sildenafil in Kidney Tx • 66% of patients believed treatment had improved their erections. • Patients reported improvements in their sexual life and partner relationships and a high level of satisfaction with treatment • Barrou 2003
Sildenafil in Kidney Tx • 30/ 51 patients (58.8%) presented with at least one SE during the study. • Most of them were mild to moderate. • Barrou 2003
Sildenafil in Kidney Tx • 5 patients (9.8%) presented with at least one serious adverse event, which led to 3 patients being withdrawn from the study. • 2 of the serious SE were considered possibly attributable to the study drug. • 1 pt angina pectoris 1 day after the beginning of treatment • 1 pt non-serious aggravated depression. • Barrou 2003
Sildenafil in Kidney Tx • At the end of the study: • 27 patients (53%) were taking a dose of 100 mg/day, • 1 patient (2%) was taking a dose of 75 mg/day, • 22 patients (43%) were taking a dose of 50 mg/day • one patient (2%) was taking a dose of 25 mg/day. • The average number of tablets taken per week between inclusion and the end of the study was 3.3+/-1.7 tablets. • Barrou 2003