IC351 (tadalafil, Cialis): update on clinical experience

IC351 (tadalafil, trade name Cialis) is a new representative compound of the second generation of selective phosphodiesterase 5 (PDE-5) inhibitors. The selectivity ratio vs PDE-5 is more than 10 000 for PDE-1 through PDE-4 and PDE-7 through PDE-10 and 780 for PDE-6. In the European daily-dosing trial, the efficacy rates were up to 93% for successful intercourses with completion in the 50-mg dose in patients with mild to moderate erectile dysfunction (ED). In two different dose-ranging studies with 2-25 mg taken as needed, efficacy rates of up to 88% improvement in erections and up to 73% successful intercourses with completion were achieved. In a placebo-controlled, fixed-dose (10- and 20-mg) trial in diabetic patients, improved erections of 56% and 64% were reported compared with 25% after placebo. Drug-related adverse effects, with headache in up to 23% of patients (placebo, up to 17%), dyspepsia in up to 11% (placebo, up to 7%), back pain in up to 4.7% (placebo, 0%), and myalgia in up to 4.1% (placebo, up to 2.4%), were mostly mild to moderate. Neither drug-related serious cardiovascular adverse events nor color vision disturbances were encountered. The long half-life (>17 h), with a comfortably long window of opportunity, releases couples from the need to plan sexual activities and therefore provides the highest amount of spontaneity for sexual activities.     

Efficacy and treatment satisfaction with on-demand tadalafil (Cialis) in men with erectile dysfunction

OBJECTIVE: Tadalafil (Cialis) is an inhibitor of phosphodiesterase type 5, which mediates relaxation of vascular smooth muscle in the corpus cavernosum thus facilitating erection. The purpose of this multicentre, randomized, double-blind, parallel group, placebo-controlled study was to evaluate efficacy and treatment satisfaction of on-demand Cialis in men with mild-to-severe erectile dysfunction (ED). METHODS: Following a 4-week treatment-free run in period, patients stratified into three severity groups by the International Index of Erectile Function (IIEF) Erectile Function (EF) domain score were randomized to receive either placebo or Cialis 20 mg taken on demand over a 12-week period. Efficacy endpoints were change from baseline in IIEF EF domain scores, responses to Sexual Encounter Profile diary (SEP) questions, and responses to the Global Assessment Questions (GAQ). Treatment satisfaction was evaluated using the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire in two of seven participating countries where validated translations were available. RESULTS: Of the 443 men who entered the trial, 409 (mean age, 52 years) formed the intent-to-treat population. Mean baseline demographics and ED severity measures were balanced between treatment groups except for a higher percentage of patients na?ve to sildenafil in the tadalafil group compared to placebo (50% versus 36%). The percentage of patients in each IIEF EF severity class (mild, moderate and severe) was 47%, 30% and 23% for placebo patients and 48%, 29% and 23% for tadalafil patients, respectively. Tadalafil was significantly superior to placebo on all primary efficacy measures (IIEF EF domain scores, SEP15, GAQ1; p < 0.001); notably 64% of tadalafil patients achieved a normal IIEF EF domain score at endpoint compared to 16% of placebo patients (p < 0.001). Of the 185 patients completing the EDITS questionnaire (137 receiving Cialis and 48 receiving placebo), tadalafil-treated patients had a median EDITS score of 84 (95%CI 80, 86), which was significantly higher than the median score for placebo-treated patients of 41 (95%CI 32, 59; p < 0.001; Wilcoxon test). The proportion of patients satisfied with treatment (defined as final EDITS score greater than 50) was 87% for the tadalafil-treated group and 46% for the placebo-treated group (p < 0.001; exact test). Adverse events were significantly more common with tadalafil than placebo (p < 0.01) and included primarily headache (7.2% versus 1.9%) and flushing (4.6% versus 0%). One patient discontinued tadalafil treatment due to back pain. CONCLUSION: In men with mild-to-severe ED, tadalafil 20 mg significantly improves erectile function, demonstrates superior treatment satisfaction relative to placebo, and is well tolerated. This is the first study to yield efficacy data on tadalafil in an Eastern European population of men with erectile dysfunction, and the first to measure satisfaction with the EDITS questionnaire in any study population of men with this condition using tadalafil.     

On-demand use of erectile aids in men with preoperative erectile dysfunction treated by whole gland prostate cryoablation

Prostate cryoablation is an established minimally invasive treatment for localized prostate cancer (PCa). However, the impairment of erectile function (EF) is considered a serious complication of the procedure. To investigate the efficacy of erectile aids following cryotherapy, 93 patients who underwent whole gland prostate cryoablation with required complete medical records were analyzed. The changes in postoperative EF were evaluated using the International Index of Erectile Function (IIEF-5) questionnaire. Additionally, independent factors that could have a correlation to the postoperative IIEF-5 score or postoperative Expanded Prostate Cancer Index Composite (EPIC) score were assessed. In the entire cohort, the mean preoperative IIEF-5 score was 7.0 ± 6.2. A total of 72 (77.4%) patients had moderate-to-severe preoperative erectile dysfunction. In longitudinal investigation, the patients using erectile aids showed the ability to recover to baseline after 24 months from cryoablation compared with the patients not using erectile aids. There were significant differences of IIEF-5 scores between these groups at 24 months (7.5 vs 3.0; P = 0.025) and 36 months (8.5 vs 3.5; P = 0.010). In multivariate analysis, the use of erectile aids correlated with restoration of IIEF-5 scores (odds ratio, 5.11; confidence interval (CI), 1.87-13.96; P < 0.001) and lower EPIC sexual bother (coef, 19.61; CI, 0.32-38.89; P = 0.046). Our data indicate that on-demand use of erectile aids could help restore EF and reduce sexual bother after whole gland prostate cryoablation. Although, erectile aids could not play a role as an adequate treatment for ED after whole gland prostate cryoablation, these results may aid in the decision-making process for PCa patients with preoperative and postoperative ED who have concern about sexual health-related quality of life.     

Pistachio diet improves erectile function parameters and serum lipid profiles in patients with erectile dysfunction

We investigated the effects of Antep pistachio on International Index of Erectile Function (IIEF) scores, penile color Doppler ultrasound (PCDU) parameters and serum lipid levels in patients with ED. A total of 17 married male patients with ED for at least 12 months were included in this prospective study. Patients were put on a 100 g pistachio nuts diet for 3 weeks. IIEF and PCDU were evaluated before and after the pistachio diet. In addition, plasma total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride were measured before and after dietary modifications from all subjects. Mean IIEF-15 score was 36 ± 7.5 before the diet and 54.2 ± 4.9 after the diet (P=0.001). Similarly, an increase in all five domains of IIEF was observed after the diet (P<0.05). Mean peak systolic velocity values before and after the pistachio diet were 35.5 ± 15.2 and 43.3 ± 12.4 cm?s(-1), respectively (P=0.018). After the pistachio diet, TC and LDL levels decreased significantly, whereas HDL level increased (P=0.008, 0.007 and 0.001, respectively). We demonstrated that a pistachio diet improved IIEF scores and PCDU parameters without any associated side effects in patients with ED. Furthermore, the lipid parameters showed statistically significant improvements after this diet.     

Evaluation of blood platelet count and function in patients with erectile dysfunction

We evaluated and compared blood total platelet count, mean platelet volume (MPV) and platelet distribution width (PDW) values of patients with erectile dysfunction (ED) and control subjects. A total 57 male patients (mean age 49.7 ± 12 years) with ED and 59 control men (mean age 49.7 ± 10.7 years) were included in the study. All patients were evaluated using medical history with International Index of Erectile Function (IIEF) scores, physical examination and routine blood analysis. Total blood count, including white blood cell (WBC), total platelet counts, MPV and PDW parameters, were recorded in both groups. MPV values were detected to be significantly higher in patients with ED than control group: 10.7 ± 1 and 9.72 ± 1.5, respectively (P = 0.001). Similarly, PDW values were significantly higher in patients with ED than control group: 14.6 ± 2.8 and 12.9 ± 1.9, respectively (P = 0.001). However, mean platelet and mean WBC counts were similar in both groups (P = 0.45). We demonstrated that MPV and PDW values significantly increased in patients with ED compared with the control group. According to these findings, platelet function might play an important role in patients with ED that warrants further research.     

Neurogenic etiology in patients with erectile dysfunction

OBJECTIVES: Erectile dysfunction (ED) is a disorder with a high prevalence that increases with age. It is estimated that 18.9% of men's between 25 and 70 years suffer it in Spain. Most cases have a multifactorial origin and it is admitted the influence on its pathogenesis of systemic diseases, different kind of drugs, psychogenic factors, cardiovascular, endocrinological and neurological diseases. Neurologic cause erectile dysfunction may have its origin in the central or peripheral nervous system. Among possible process of neurogenic erectile dysfunction of central origin would be tumors, cerebral vascular accidents, encephalitis, Parkinson disease, multiple sclerosis and other demyelinization diseases, dementias, olivopontocerebellar degeneration and epilepsy. Myelopathies of any etiology may be, depending on their localization and extension, cause of erectile dysfunction. At the peripheral level, disorders of the sensitive tracts constituting the afferent limb of the erection spinal reflex, and the efferent vegetative or somatic tracts mediating arterial vasodilatation, cavernous smooth muscle relaxation or pelvic floor striated muscle contraction. The aim of this work is to review in detail the most relevant causes of neurogenic erectile dysfunction, their etiopathogenic mechanisms and therapeutic approaches currently considered more adequate for each particular case. CONCLUSIONS: The correct diagnostic approach to patients with erectile dysfunction passes through identification, if possible, of the etiopathogenic factors implied. Regarding this, detection and identification of a possible neurogenic risk factor will contribute to a better understanding of the physiopathologic mechanisms, and more adequate diagnostic, prognostic and therapeutic approaches, mainly in those patients refractory to first line therapy.     

Paraoxonase activity in patients with erectile dysfunction

Paraoxonase (PON1) is a high-density lipoprotein (HDL)-associated enzyme that protects low-density lipoprotein (LDL) and HDL from peroxidation. In this study, PON1 activities were determined in patients with erectile dysfunction (ED) to investigate the relationship between ED and atherosclerosis. Forty patients, who had been diagnosed with ED by the medical and sexual anamnesis and routine laboratory tests, were included in the study. Thirty healthy, sexually active, married and age-matched men were selected as the control group. The patients and controls who underwent surgical or medical treatment in 1-week time and had a systemic disease such as malignancy, liver and renal insufficiency, and active infection and who smoked cigarettes were excluded. PON1 activities were measured spectrophotometrically. Unpaired samples t-test, correlation analyses and multiple linear regression analyses were used for statistical analyses. The results are given as mean+/-standard deviation of mean. The mean ages of the patient and the control groups were 31.05+/-6.90 (range 22-51) and 29.40+/-6.26 (range 19-46), respectively (P=0.307). Serum PON1 levels of the patient and the control groups were found to be 119.05+/-62.11 and 185.04+/-55.64, respectively. The difference between the groups was quite significant (P=0.001). Epidemiological and experimental studies indicate that PON1 activation was lower in individuals who had a tendency to develop atherosclerosis due to comorbidities such as diabetes, familial hypercholesterolemia and kidney disease. In this study, PON1 activity level was found to be significantly lower in ED patients than in control group. The decrease of PON1 activity may have a role in the ethiopathogenesis of ED, and the atherosclerosis development may be faster in the patients due to decreased activity of PON1, which is an antiatherogenic enzyme.     

Residual renal function and erectile dysfunction in patients on hemodialysis

Introduction

Residual renal function and erectile dysfunction are important parameters of quality of life in dialysis patients.

Goal

The purpose of our investigation was to determine correlations between erectile dysfunction and residual diuresis in patients on hemodialysis.

Methods

The survey was organized as a cross-sectional study in men aged up to 65?years on hemodialysis. All respondents voluntarily completed the questionnaire of the International Index of Erectile Function (IIEF)-5. Demographic and anthropometric characteristics, the duration of dialysis, smoking, alcohol consumption, residual renal function, comorbidity, and routine biochemical parameters were determined for all patients. The adequacy of dialysis was calculated as Kt/V. Based on residual renal function, the patients were divided into a group without residual diuresis and a group with preserved residual renal function.

Results

Nearly two-thirds of our patients did not have preserved diuresis, while 82.8% of our respondents had erectile dysfunction. Patients with preserved residual renal function were heavier (P?=?0.047) and had higher body mass index (P?=?0.047), but the prevalence of cardiovascular disease (P?<?0.0001) and erectile dysfunction (P?<?0.0015) was lower, compared to patients without residual diuresis. The regression model also demonstrated a statistically significant relationship between the residual diuresis and the total IIEF score (b?=?4.74; P?<?0.001).

Conclusion

Hemodialysis patients with preserved diuresis retain erectile function better.     

The relationship between serum irisin levels and erectile dysfunction in diabetic men (irisin and erectile dysfunction in diabetic patients)

Irisin is an exercise-induced myokine that alleviates endothelial dysfunction and reduces insulin resistance in type 2 diabetes mellitus. We conducted this cross-sectional prospective study to determine the association of serum irisin levels and erectile dysfunction in type 2 diabetic patients. We compared 34 diabetic patients with erectile dysfunction with 30 diabetic patients without erectile dysfunction. In our study, serum irisin levels were found to be statistically significantly higher in diabetic patients without erectile dysfunction compared to those with erectile dysfunction (p = .016) and according to correlation analysis, irisin levels had a significantly negative correlation with the serum HbA1C value (r = −.294, p = .018). Based on the results of our study, we think that this molecule can be used in the diagnosis or treatment of erectile dysfunction in diabetic patients, if these findings are supported by larger studies.     

Sildenafil use in patients with olanzapine-induced erectile dysfunction

In the present study, we aimed to examine the efficacy of sildenafil in patients with an antipsychotic (olanzapine)-induced erectile dysfunction (ED). The study group comprised 10 patients who experienced ED associated with the use of olanzapine. The patients initially received 50 mg sildenafil at baseline. If clinically indicated, titration up to 100 mg was permitted. All patients were assessed by Clinical Global Impression-Improvement (CGI-I) and International Index of Erectile Dysfunction (IIEF) scales at baseline and weeks 2 and 4. At final assessment, three patients were considered 'very much improved' and four 'much improved' according to CGI-I. Our results suggest that sildenafil use is effective and well-tolerated in patients with olanzapine-induced ED.     

阴茎微循环检测在阳痿诊断中的价值

目的：探讨阴茎头微循环检测在阳痿诊断中的意义。方法：检测２２例勃起功能障碍病人的阴茎微循环,与１７例健康志愿者进行比较。结果：血管性阳痿病人阴茎头微血管密度（２６．８±６．３ｖｓ４７．８±６．２,Ｐ＜０．０１）和异常微血管百分率（３３．２±３．６ｖｓ１２．８±１．３,Ｐ＜０．０１）与对照组相比有显著性差异;心理性阳痿病人的两项指标（微血管密度４７．２±６．８ｖｓ４７．８±６．２,Ｐ＞０．０５;异常微血管百分率１３．１±１．１ｖｓ１２．８±１．３,Ｐ＞０．０５）与对照组相比没有统计学差异。结论：阴茎头微循环障碍与阳痿病人的器质性改变有关,阴茎头微循环检测可用于血管性阳痿的辅助诊断。     

男子勃起功能障碍病人阴茎微循环检测

检测26例勃起功能障碍（ED）病人的阴茎微循环，与17例健康志愿者进行比较，器质性ED病人阴茎头微血管密度为271±5．2，健康者为47．8±6．2（P＜0．01）；异常微血管百分率则分别为32．1±3．4与12．8±1．3（P＜0．01）；心理性ED病人该两项指标与对照组相比没有统计学差异（血管密度47．2±6.8vs47．8±6．2．P＞0．05；异常血管百分率13．1±1．1vs12．8±1．3．P＞0．05）。以上结果揭示，阴茎头微循环障碍与ED病人的器质性改变有关，可用于器质性ED的辅助诊断。     

Sympathetic skin response in patients with erectile dysfunction

OBJECTIVES

To evaluate the role of the sympathetic skin response (SSR) in men with erectile dysfunction (ED), focusing on detecting SSR in the penis.

PATIENTS AND METHODS

We assessed the SSR in 82 patients with ED, as an indicator of abnormalities both in amyelinic C‐fibres and in autonomic pathways in these patients. The SSR was carried out according to the to the Technical Standards of the International Federation of Clinical Neurophysiology. Electrical stimulation was applied through superficial electrodes over the contralateral median nerve. Values were recorded with superficial electrodes on the skin in the contralateral hand and foot, as well as in the penis. The percentage of SSR (SSR%) was classified into three groups, i.e. 0–20%, 21–89% and 90–100%. Results of latency were also classified into three groups of normal or abnormal (increased) latency, and response blocking (no response), the last two being considered pathological conditions.

RESULTS

In the penis, the mean (sd ) SSR% was 52.8 (43.19)% and significantly lower than responses in hands and feet. There was a significant correlation of the SSR% between the palm of the hand and the sole of the foot (P = 0.01) and between the sole of foot and penis (P = 0.05). Diabetics showed a significant decrease (P = 0.001) in the mean SSR% in the palm of the hand and sole of the foot. Although not statistically different, the mean SSR% in the penis was lower in diabetics than in patients with other risk factors for ED. Likewise, the mean SSR% in hand, foot and penis increased with an increase in the International Index of Erectile Function. In the penis, latency was normal (<1.5 ms) in 14 and abnormal in 37 patients. There was a significant association between pathological chronic re‐innervation in the bulbocavernosus muscle and SSR latencies in the foot (P = 0.002) and penis (P = 0.03). Bulbocavernosus muscle electromyography showed a higher frequency of chronic bilateral axonomnesis in patients with abnormal latencies (28%) than in patients with normal SSR latencies in the penis.

CONCLUSION

These results establish an indication of the SSR in patients with ED, registering responses not only in classic locations like the palm of the hand or sole of the foot, but also in the penis. The SSR% was useful as an indicator of the effect on efferent C fibres. Despite SSR being a polysynaptic potential of long latency and regulated by the cerebral cortex, the present results show that it is advisable to record the latencies of SSR in the three areas registered, and especially in the penis, where it seems be more useful as a marker of lumbosacral and/or pudendal alterations.     

阴茎勃起障碍患者对西地那非用药依从性的研究

目的了解阴茎勃起功能障碍(ED)患者对西地那非用药的依从性以及健康教育对依从性的影响。方法216例ED患者随机分为健康教育联合药物组(甲组)和药物组(乙组),疗程2月。分别对治疗前、治疗期间、治疗后的依从性进行评价。结果216例患者中,117例(54.2%)愿意接受西地那非治疗,甲组的接受率显著高于乙组(69.6%:36.6%;P<0.001)。这117例在治疗期间的依从率为57.3%,两组比较有显著性差异(66.3%:37.8%;P<0.001)。治疗2月后,31.6%的患者表示愿意继续接受西地那非治疗,甲组的接受率显著高于乙组(37.5%:18.9%;P<0.05)。认为疗效不理想、担心药物的不良反应和经济原因是影响依从性的主要因素。结论ED患者对西地那非治疗的依从性差,健康教育有助于改善依从性。