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PubMed2001

The incidence of pharmacologically induced priapism in the diagnostic and therapeutic management of 685 men with erectile dysfunction.

OBJECTIVE: To evaluate the incidence of pharmacologically induced priapism in the diagnostic and therapeutic management of erectile dysfunction. PATIENTS AND METHODS: Over a period of 7 years, 685 men were investigated for erectile failure. They underwent a simple test with vaso-active drugs, and the nonresponders were further investigated. Eventually, 83 men began autoinjections and 45 still continue. RESULTS: Eight (1.2%) cases of priapism presented during the simple test with vaso-active drugs in these patients, while none occurred during self-injection treatment. Three were prolonged erections induced by prostaglandin E1 (PGE1) and 5 by papaverine (Pap). Six were treated safely with intracavernosal injection of etilephrine without blood aspiration. CONCLUSION: Priapism is always a potential phenomenon where no individual, no particular drug and no specific dose are completely safe. It may be caused even with 5 microg of PGE1 or 7.5 mg of Pap. Auto-injection therapy however is a safe kind of treatment in well-experienced patients. Careful regulation of the doses and practice in the use of vaso-active drugs may reduce the priapism rate.

Adult↗

PubMed2001

The efficacy of sildenafil in different etiologies of erectile dysfunction.

PURPOSE: The aim of this study was to evaluate the efficacy of sildenafil and success of treatment in particular etiological causes in erectile dysfunction lasting more than 3 months. MATERIAL AND METHODS: A total of 141 patients between 27 and 78 years old without any cardiac compromise, despite controversial, which precludes sildenafil (Viagra) treatment, were included in this study. All patients had only International Index of Erectile Capacity Form (IIEF) for pre-treatment evaluation and 50 mg sildenafil was started. Patients were assessed monthly for 6 months thereafter. Erectile capacity changes were questioned by IIEF on each follow-up and 100 mg sildenafil was given in patients without a response and monthly follow-up was scheduled. All patients had SMA-12, hormonal analyses and penile colour Doppler ultrasonography during the treatment course. The difference between IIEF score of each patient was displayed by Paired-t test and p-values less than 0.05 was applied as significant. RESULTS: The average beginning IIEF score of 141 patients was 11.80 +/- 0.47 [6-22], and increased to 20.70 +/- 0.62 [6-30] after a month of 50 mg sildenafil treatment. The mean increase was 75.4% and found to be significant (p = 0.000, p < 0.05). The average IIEF scores were recorded as 22.57 +/- 0.69 after 3, and 22.12 +/- 0.24 after 6 months. There was no difference between these values and 2nd month controls (P3 month = 0.5675, P6 month = 0.6138, p > 0.05). A positive response was recorded in 102 patients (72.3%) and 39 (27.7%) patients were unresponsive. Doubled doses of sildenafil (100 mg) was effective in additional 17 patients. After overall treatment, 119 (84.4%) patients had benefit from sildenafil. Penile Doppler ultrasonography displayed arterial insufficiency in 79 (56.03%), veno-occlusive dysfunction in 14 (9.93%), mixt vascular pathology in 14 (9.93%) patients. Normal ultrasonographic findings in 32 patients (22.7%) were classified as psychogenic dysfunction. Among the organic causes, sildenafil was found to be most effective in arterial insufficiency group. CONCLUSION: Sildenafil is a successful management modality in erectile dysfunction with minimal pre-treatment evaluation. As far as etiological causes concerned, sildenafil was found to be most effective in arterial insufficiency group and psychogenic group. The efficacy of sildenafil treatment has not been changed with the treatment time, since IIEF scores were stable during follow-up controls.

Adult↗

PubMed2004

Erectile dysfunction in hemodialysis patients with diabetes mellitus: association with age and hemoglobin A1c levels.

AIM: Erectile dysfunction (ED) is common in patients with diabetes mellitus (DM) as well as those undergoing hemodialysis (HD). The purpose of this study is to investigate the frequency and severity of ED in HD patients with DM and those without DM. In addition, we examined the relationship between erectile function and several risk factors, including presence of DM and hemoglobin A1c levels in HD patients. METHODS: This study involved 180 patients on HD, including 66 HD patients with DM (DM-HD) and 114 patients without DM (non-DM-HD). We evaluated erectile function using an abridged five-item version of the international index of erectile function (IIEF-5). Logistic regression analysis was used to investigate the relationship between presence of ED and several risk factors. RESULTS: The total score of IIEF-5 in DM-HD patients (9.5 +/- 4.2) was significantly lower than in non-DM-HD patients (13.5 +/- 5.7). The prevalence of severe ED was 42.4% and 18.4% in DM-HD patients and non-DM-HD patients, respectively. Age, cardiovascular disease history, and DM were identified as independent risk factors for the presence of ED. Furthermore, age and elevated hemoglobin A1c levels were identified as independent risk factors for the presence of severe ED. CONCLUSION: DM-HD patients are more likely to have ED, and particularly severe forms of ED, than non-DM-HD patients. DM and elevated hemoglobin A1c levels were associated with the presence of ED or severe ED, respectively. Aging was identified as an independent factor in both ED and severe ED.

Age Factors↗

PubMedDate not supplied

Sildenafil improves quality of life in men with heart failure and erectile dysfunction.

Patients with congestive heart failure (CHF) have specific factors that enhance the risk for erectile dysfunction (ED), such as low cardiac output and the use of drugs with vasodilator effect. ED can negatively affect interpersonal relationships and self-esteem, with significant impact on the quality of life. We hypothesized that the improvement of the sexual dysfunction would enhance the quality of life of individuals with systolic heart failure. This is a prospective study of 12 male CHF patients using a fixed dose of sildenafil during 1 month. Patients were included if they had left ventricular ejection fraction lower than 40% documented by echocardiography and International Index of Erectile Function (IIEF) score lower than 21. The effect of sildenafil in quality of life was evaluated by the Minnesota questionnaire. Improvement in ED was assessed using the IIEF. The mean IIEF5 score was 9.6 (+/-3.8) before the use of sildenafil and 19.3 (+/-4.3) after sildenafil (P = 0.0001). The mean Minnesota score was 28.75 (+/-21) before treatment and 12.75 (+/-10.1) after the intervention (P = 0.012). In conclusion, the sexual function improvement provided by sildenafil enhances quality of life in individuals with systolic heart failure.

Aged↗

PubMed2000

Yohimbine in erectile dysfunction: the facts.

Yohimbine, a pharmacologically well-characterized alpha-2-adrenoceptor antagonist with activity in the central and peripheral nervous system, has been used for over a century in the treatment of erectile dysfunction. In-depth, systematic studies in animals have shown that the drug has a remarkable positive effect on sexual performance. Meta-analyses of the few controlled, randomized human studies have consistently shown an advantage of yohimbine over placebo. Despite such a long history and encouraging activity, the drug has not yet been subjected to scientifically rigorous human clinical trials. Although relevant basic pharmacological and animal research information has been available for over 15 y, recent studies were designed with a lack of insight and complete disregard of those fundamental studies. Currently, dose-response investigations are not available, alternative routes of administration (i.e. sublingual) have not been investigated, nor has continuous versus 'on-demand' administration been explored. Synergistic activity with other drugs was last studied nearly four decades ago. Assessment of various populations was carried out in very limited cohorts and only in most general terms. In short, properly designed trials in humans have not been done. Why? Yohimbine is an old drug. As such it does not enjoy patent protection or commercial viability. Until molecular/formulation changes can be brought about (as recently happened with two other agents: phentolamine and apomorphine), serious investigations of yohimbine will remain in limbo. It could be that the nay sayers are right and yohimbine, indeed, lacks clinical activity as a treatment for men with erectile dysfunction. As long as it remains an orphan drug, we will never know. International Journal of Impotence Research (2000) 12, Suppl 1, S70-S74

Journal Article↗

PubMedDate not supplied

Erectile dysfunction in early, middle, and late adulthood: symptom patterns and psychosocial correlates.

The prevalence of erectile dysfunction (ED) increases with age. However, it may emerge at any time during the adult years, and may bear a close relationship to ongoing psychosocial issues affecting the patient and his partner. The present study examined ED symptomatology and its associated psychosocial context in 560 men aged 19-87 attending a urology clinic for erectile difficulties. We divided participants into three age groups: early adulthood (age 19-39); middle adulthood (40-59); and late adulthood (60+). They completed a self-report assessment battery evaluating medical, psychological, and lifestyle factors empirically or theoretically related to ED. Results showed that although younger men reported more positive overall ratings of their sex life and better overall erectile functioning relative to older men, they also reported comparatively less relationship satisfaction, greater depressive symptomatology, more negative reactions from partners, and less job satisfaction. Results suggest that older men experience less difficulty than younger men adjusting to life with ED.

Adult↗

PubMed2006

Can atorvastatin improve the response to sildenafil in men with erectile dysfunction not initially responsive to sildenafil? Hypothesis and pilot trial results.

BACKGROUND: Erectile dysfunction (ED) may be one manifestation of a generalized vascular disorder characterized by endothelial dysfunction. Statin drugs may improve endothelial function, even before altering the lipid profile. OBJECTIVE: We sought to determine whether the addition of a statin with sildenafil would improve ED in men who initially responded poorly to sildenafil. METHODS: Men with moderate-to-severe ED despite an adequate sildenafil trial were enrolled in this randomized, double-blind, placebo-controlled pilot study. ED was defined using a validated self-administered questionnaire as a score of <or=16 on the International Index of Erectile Function (erectile function domain score range of 6-30). Improvement in ED score with sildenafil was reassessed at 6 and 12 weeks of treatment with atorvastatin (80 mg daily) or matching placebo. RESULTS: Twelve men (mean age 58 +/- 13 years) with a mean domain score of 8.2 +/- 6.9 and a mean duration of ED of 3.7 years were enrolled in the study. Treatment with atorvastatin decreased mean low-density lipoprotein cholesterol by 43% and resulted in an improvement with sildenafil in domain score of 7.8 (P = 0.036); an effect was apparent by 6 weeks. The increase in domain score in placebo patients was not statistically significant. CONCLUSIONS: Treatment with atorvastatin improved sexual function and the response to oral sildenafil in men who did not initially respond to treatment with sildenafil. The results of this pilot study support the hypothesis that vascular endothelial dysfunction contributes to ED in sildenafil nonresponders and deserves further testing in a large clinical trial.

Adult↗

PubMed2005

Relationships between erectile dysfunction, depression, and anxiety in Japanese subjects.

AIMS: This study aimed to elucidate the relationships between erectile dysfunction (ED) and depression or anxiety. METHODS: Subjects were 1,419 Japanese men aged 40-64 years. ED was assessed by the International Index of Erectile Function 5 (IIEF-5) score (Japanese version), and depression and anxiety symptoms were assessed by the Hospital Anxiety and Depression Scale (HADS). In this study ED cases were defined as those whose IIEF-5 value was less than 12, and a score of 8 or higher was used to classify a subject as suffering from depression or anxiety, respectively. The prevalence odds ratio (OR) of ED was calculated with confidence interval (CI) estimated by the Woolf's method by five age groups (40-44, 45-49, 50-54, 55-59, 60-64 years). To control for age, body mass index, smoking, and alcohol drinking factors, we conducted the multivariate logistic regression analysis for calculating adjusted ORs and 99% CIs. RESULTS: ED was significantly associated with depression in age groups 45-49 (OR 3.42, 99% CI 1.51-7.76) and 50-54 years (OR 2.43, 99% CI 1.11-5.35). After using multivariate analysis, adjusted OR also showed statistical significance. (OR 2.02, 99% CI 1.32-3.08). ED was significantly associated with anxiety in the 50-55-year-old age group (OR 2.48, 99% CI 1.12-5.47). After using multivariate analysis, adjusted OR also showed statistical significance (OR 1.77, 99% CI 1.15-2.72). The concomitant depression and anxiety group (A+D+) had significantly higher prevalence of ED than the control group (A-D-) in both the 45-49 and 50-54 age groups. (P < 0.01) CONCLUSION: ED associated significantly with depression and anxiety status only in late 40s to early 50s (45-55 years) in male Japanese. Furthermore, comorbidities of depression and anxiety strengthen this association. Our results might be useful in furthering understanding of ED etiology and determining a target population for prevention in ED subjects.

Adult↗

PubMed2004

Androgen, estrogen, and progesterone receptor gene regulation during diabetic erectile dysfunction and insulin treatment.

OBJECTIVES: To determine whether altered levels of sex hormone receptor genes (androgen, estrogen, and progesterone receptors) are involved in the etiology of diabetes-related erectile dysfunction. Insulin treatment can restore erectile function through modulation of sex hormone receptor genes. METHODS: Diabetes was induced in rats (n = 40) by intraperitoneal injection of streptozotocin. The diabetic rats were divided into two groups: untreated rats (n = 20) and rats treated daily with 10 U subcutaneous human recombinant insulin (n = 20). Control nondiabetic rats (n = 20) were given only vehicle. Erectile function was analyzed by measurement of intracavernous pressure. Gene and protein expression of sex hormone receptors were analyzed by reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. RESULTS: The mean intracavernous pressure was significantly decreased in the diabetic rats compared with the controls and was restored to normal after insulin treatment. In the diabetic rat crura, mRNA and protein expression for estrogen receptor-beta and progesterone receptor were significantly lower than in the control crura, and the expression profile of androgen receptor and estrogen receptor-beta did not change. Insulin treatment restored estrogen receptor-beta and progesterone receptor mRNA and protein expression. Insulin treatment significantly increased the expression of mRNA and protein for androgen receptor and estrogen receptor-alpha in diabetic rats compared with control rats. CONCLUSIONS: This is the first study to demonstrate that insulin treatment may restore erectile function through restoration of sex hormone receptor gene and protein expression in the diabetic rat crura.

Animals↗

PubMed1995

Efficacy of linsidomine chlorhydrate, a direct nitric oxide donor, in the treatment of human erectile dysfunction: results of a double-blind cross over trial.

Recent experimental work has demonstrated that nitric oxide (NO) is the neurotransmitter responsible for cavernous smooth muscle relaxation. Different studies on the performance of the direct NO-donor SIN-1 (linsidomine chlorhydrate) in patients with erectile dysfunction have come to conflicting results. We have performed a double-blind cross over trial in 40 patients with erectile dysfunction of mixed etiology comparing SIN-1, SIN-1 plus the alpha-blocker Urapidil, and prostaglandin E1 (PGE1) in order to determine the effectiveness of SIN-1. PGE1 achieved the best response, the combination of SIN-1 and Urapidil performed slightly, statistically insignificantly poorer with significantly increased side effects. SIN-1 alone performed statistically significantly (p < 0.0068) worse. SIN-1 is not a useful alternative to PGE1. The combination of SIN-1 and Urapidil performs equally as good as PGE1 but cannot be recommended due to intolerable side effects.

Adult↗

PubMed2004

Do cigarette smokers with erectile dysfunction benefit from stopping?: a prospective study.

OBJECTIVE: To assess whether stopping smoking can improve erectile dysfunction (ED) in smokers, as cigarette smoking is a known risk factor for ED. PATIENTS AND METHODS: Smokers who requested nicotine replacement therapy (NRT) and complained of ED were first evaluated for hypertension, dyslipidaemia, diabetes, psychiatric disorders and drug history. The grade of ED in smokers with none of these risk factors was then determined using the five-item version of the International Index of Erectile Function (IIEF-5) before NRT, and the grading repeated after 1 year of follow-up. The correlation between the exposure to smoking (pack-years) and severity of ED was assessed before the follow-up. The ED status between patients who stopped smoking after NRT and those who continued during the follow-up was then compared before and after the follow-up. RESULTS: The severity of ED correlated significantly with the level of exposure to smoking. Age and ED status before the follow-up were not significantly different between 118 patients who stopped (ex-smokers) and 163 who continued smoking (current smokers). After 1 year the ED status improved in > or = 25% of ex-smokers but in none of the current smokers; 2.5% of ex-smokers and 6.8% of current smokers had a deterioration in ED. Ex-smokers had a significantly better ED status after the follow-up (P = 0.009). Among ex-smokers, patients with advanced ED and those who were older had less improvement. CONCLUSION: There is a strong association between the intensity of cigarette smoking and degree of ED. Stopping cigarette smoking can improve ED in a considerable proportion of smokers. Age and the severity of ED before stopping are inversely related to the chance of improvement.

Adult↗

PubMed2003

Safety and efficacy of vardenafil for the treatment of men with erectile dysfunction after radical retropubic prostatectomy.

PURPOSE: More than one-third of men may experience erectile dysfunction (ED) after nerve sparing radical retropubic prostatectomy. The efficacy and safety of vardenafil, a potent, selective, phosphodiesterase 5 inhibitor, was assessed for the treatment of ED after radical prostatectomy. MATERIALS AND METHODS: In this double-blind study 440 men with ED after nerve sparing radical prostatectomy were randomized to take placebo, or 10 or 20 mg vardenafil. Efficacy was measured after 12 weeks using the erectile function domain of the International Index of Erectile Function, diary questions measuring vaginal penetration and intercourse success rates, and a global assessment question (GAQ) on erection. RESULTS: Of the intent to treat population 70% had severe ED (erectile function less than 11) at baseline. After 12 weeks both vardenafil doses were significantly superior to placebo (p <0.0001) for all efficacy variables. Improved erections (based on GAQ) were reported by 65.2% and 59.4% of patients on 20 and 10 mg vardenafil, respectively, and by only 12.5% of patients on placebo (p <0.0001). Among men with bilateral neurovascular bundle sparing, positive GAQ responses were reported by 71.1% and 59.7% of patients on 20 and 10 mg vardenafil, respectively, versus 11.5% of those on placebo (p <0.0001). The average intercourse success rate per patient receiving 20 mg vardenafil was 74% in men with mild to moderate ED and 28% in men with severe ED, compared to 49% and 4% for placebo, respectively. Few adverse events were observed. They were generally mild to moderate headache, flushing and rhinitis. CONCLUSIONS: In men with severe ED after nerve sparing radical retropubic prostatectomy, vardenafil significantly improved key indices of erectile function.

Double-Blind Method↗

PubMed2000

Screening for erectile dysfunction: rationale.

A number of epidemiologic and clinical studies that have examined the relationship between erectile dysfunction, depression and cardiovascular disease are reviewed. Hypothetical mechanisms that can explain the correlations observed among these phenomena are described and a mutually reinforcing predictive model is proposed. International Journal of Impotence Research (2000) 12, Suppl 4, S147-S151.

Cardiovascular Diseases↗

PubMed2002

Phosphodiesterase type 5 as a pharmacologic target in erectile dysfunction.

The scientific rationale of pharmacologically inhibiting phosphodiesterase type 5 (PDE5) in the treatment of erectile dysfunction (ED) is reviewed. Published literature on the nitric oxide-cyclic guanosine monophosphate (cGMP) pathway for penile erection and on PDE5 inhibition using sildenafil as the model for pharmacologic PDE5 inhibition are assessed. The key second messenger in the mediation of penile erection is cGMP. PDE5 is the predominant PDE in the corpus cavernosum, and cGMP is its primary substrate. Therefore, in men with ED, elevation of cGMP in corpus cavernosal tissue via selective inhibition of cGMP-specific PDE5 is a means of improving erectile function at minimal risk of adverse events. This approach is validated by the clinical efficacy and safety of sildenafil, the pioneering drug for selective PDE5 inhibitor therapy for ED. Sildenafil exhibits inhibitory potency against PDE5 and a 10-fold lower dose-related inhibitory potency against rod outer segment PDE6, the predominant PDE in the phototransduction cascade in rods. Thus, its pharmacologic profile is predictable, with close correlation between pharmacodynamic and pharmacokinetic properties. Clinically, sildenafil improves erectile function in a large percentage of men with ED. The most common adverse events are due to PDE5 inhibition in vascular and visceral smooth muscle; similar adverse events are expected during therapeutic use of all PDE5 inhibitors. As free sildenafil plasma concentrations approach concentrations sufficient to inhibit retinal PDE6, usually at higher therapeutic doses, transient, reversible visual adverse events can occur, albeit infrequently. Selective inhibition of PDE5 is a rational therapeutic approach in ED, as proved by the clinical success of sildenafil.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2000

Erectile dysfunction in the ageing man.

Most studies have shown an increase in the prevalence of erectile dysfunction with ageing. Penile erection is a vascular phenomenon resulting from smooth muscle relaxation, arterial dilatation and venous restriction. The atherosclerosis of the penis that occurs with ageing causes a decrease in penile oxygen tension. This change in oxygen tension impacts directly upon both the physiologic function and the trabecular structure of the corpora cavernosa. Chronic ischaemia of the penis is associated with fibrosis of smooth muscle fibres and with endothelial and neuronal NO/cGMP pathways. The effects of androgens on libido and sexual behaviour are well established but their role in the erectile mechanism remains unclear. The histologic and haemodynamic causes responsible for the erectile decline in the ageing man are reviewed.

Age Factors↗

PubMed2002

Economic aspects of medical erectile dysfunction therapies.

The introduction of safe and effective oral therapies has changed the significance of erectile dysfunction (ED) forever. Seldom has a new drug changed the landscape of pharmacotherapy in so many ways as sildenafil (Viagra, Pfizer). This article highlights the various oral, intracavernosal and intraurethral therapies currently available for ED and evaluates the socio-economic impact of each method.

Apomorphine↗

PubMed2003

Overview of phosphodiesterase 5 inhibition in erectile dysfunction.

Since the early 1980s, research on the mechanisms of penile erection has done much to clarify erectile physiology and pathophysiology. More recent studies have identified the importance of neurochemical mediators in erection. These include the nitric oxide-cyclic guanosine monophosphate (cGMP) cell-signaling system-a complex molecular pathway that mediates smooth muscle relaxation in the corpus cavernosum. Phosphodiesterase 5 (PDE5) inactivates cGMP, which terminates nitric oxide-cGMP-mediated smooth muscle relaxation. Inhibition of PDE5 is expected to enhance penile erection by preventing cGMP degradation. Development of pharmacologic agents with this effect has closely paralleled the emerging science. The prototype of this new therapeutic class of PDE5 inhibitors is sildenafil, which was approved for treatment of erectile dysfunction in 1998. Tadalafil and vardenafil are new agents in this class. These agents have demonstrated improvement in erectile function and have been shown to be well tolerated in diverse populations comprising thousands of men worldwide. Profiles of these 3 PDE5 inhibitors are reviewed herein.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2003

[Expandable penile implants in patients with erectile dysfunction].

Modern medical treatment can restore normal sexual function in the majority of men with erectile dysfunction, but some men will not obtain an erection sufficient for sexual intercourse. In some of these men, with a strong desire to have an active sexual life including intercourse, it is possible to restore the function by the use of a penile implant. We describe the indications, the surgical procedure and the results with an expandable penile implant.

Erectile Dysfunction↗