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PubMed1998

Phosphodiesterase inhibitors in the treatment of erectile dysfunction.

Based on knowledge of intracellular signal propagation in cavernous smooth muscle tone regulation and the development of new and selective pharmacological agents, selective phosphodiesterase (PDE) inhibitors were recently introduced for the treatment of erectile dysfunction. By molecular biological methods, PDE isoenzymes III, IV and V were characterized in the human cavernous smooth muscles. In functional organ bath studies using precontracted human cavernous tissue strips, PDE III and V inhibitors showed the most pronounced relaxant responses. In clinical studies, the use of the orally active PDE V inhibitor sildenafil induced a pronounced and significant erectogenic effect in patients with both predominantly psychogenic and organogenic etiology of erectile dysfunction. The first promising clinical data on the use of an orally active PDE inhibitor for the treatment of erectile dysfunction are well supported by consistent basic science findings. Further research will possibly allow to identify diagnostic tools for erectile dysfunction and for even more selective drugs in its therapy.

Journal Article↗

PubMed2001

[Intracavernous injections in the treatment of erectile dysfunction in spinal cord injured patients: experience with 36 patients].

OBJECTIVES: To confirm the efficiency of intracavernous injections in the treatment of erectile dysfunction in spinal cord injured (SCI) patients and to determine the mean necessary dose to obtain functional erection. MATERIALS: This prospective study concerns 36 spinal cord injured men. None of them had erectile dysfunction before the neurologic impairement. Sixty four intracavernous injections were performed. METHOD: The first injection was done with the usually recommended starting dose. The injections were then repeated with increasing dosage to archive a rigid erection. The erection was evaluated with Schramek grading. A grade 4 or 5 erection was considered as functional. RESULTS: Nine tetraplegics and 27 paraplegics were included. Twenty two were grade A in ASIA classification. The mean age was 31 years. Twenty for patients had a level above T10, 11 between T11 and L2, one below L2. Twenty seven patients obtained an erection of grade 4 or 5. Alprostadil was used 51 times, moxisylite nine times and papaverine four times. The average dose necessary to obtain a grade 4 or 5 functional erection adequate for coitus was 12.3 +/- 4.8 microgram with alprostadil and 14 +/- 5.4 mg with moxisylite. No side effects were noted. The nine left patients did not archive satisfying erection during this study. No clinical differences were noted in this population, compared with the 27 other patients. CONCLUSION: The findings confirm the efficiency of intracavernous injections in the management of erectile dysfunction in SCI. The average doses required to obtain a functional erection was 12.3 (+/- 4.8) microgram with alprostadil and 14 (+/- 5.4) mg with moxisylyte.

Adult↗

PubMed1998

[Yohimbine in therapy of erectile dysfunction].

The bark of the yohimbine tree has long been appreciated as an aphrodisiac. Recent studies have shown that yohimbine is effective in the symptomatic treatment of erectile dysfunction. It is superior to placebo and has fewer side effects compared with the invasive treatment of erectile dysfunction. The evidence for effectiveness seems less compelling for other oral drugs used in this condition. It can be concluded that yohimbine is an attractive option in the symptomatic treatment of erectile dysfunction.

Administration, Oral↗

PubMed1994

[Etiological analysis of male diabetic erectile dysfunction with particular emphasis on findings of vascular and neurological examinations].

We studied the nocturnal penile tumescence (NPT) value obtained by simple method and the vascular and neurological findings closely related to the ability to achieve/maintain an erection in order to investigate the causative factors of organic erectile dysfunction seen in diabetes. Studies were carried out on 62 male diabetics (32-78 y.o.). The results were as follows. 1. There were no cases of a decrease in the nocturnal penile tumescence (NPT) value among eight subjects who showed no erectile dysfunction. However, a decrease in the NPT value was recorded in 28 (85%) of 34 subjects who showed complete failure to achieve/maintain an erection. It was, therefore, surmised that there is a large organic contribution to the erectile dysfunction seen in diabetes. 2. We determined the penile blood pressure index (PBPI), the reactions of papaverine tests, conduction velocity of the dorsal nerve of the penis and the latency of the bulbocavernosus reflex. 42 (67.7%) of the 62 subjects had penile vascular disorders and the cases with severe vascular disorders were skewed to the high age brackets. There were also many cases with neuropathy involved in the ability to achieve/maintain an erection: 38 (61.2%) of the 62 subjects. Moreover, many of the subjects were found to have damage to both the blood vessels and the nerves relating to an erection, and these forms of damage were surmised to be deeply involved in the decrease in the NPT value. 3. Multivariate analysis indicated that the most important factor involved in the decrease in the NPT value was vascular damage (contribution rate: 30.8%), followed by neuropathy (6.9%). These two factors represented the most important explanatory factors of the organic erectile dysfunction seen in diabetes. 4. The contribution rate of vascular damage to the decrease in the NPT value was 18.8% for diabetic subjects under the age of 60 years, but 45.1% for subjects aged 60 years or more. The contribution rate was thus higher in the elderly subject group. On the other hand, the contribution rate of neuropathy to the decrease in the NPT value was 7.7% for diabetic subjects under the age of 60 years, but the rate decreased to 4.7% for subjects aged 60 years or more.

Adult↗

PubMedDate not supplied

Environmental agents and erectile dysfunction: a study in a consulting population.

We evaluated chemical and physical environmental agents as risk factors for erectile dysfunction among a consulting population. We studied 199 men who sought medical help for erectile disorders between 1996 and 1998 in 3 andrology units in the Litoral Sur region of Argentina. Patients were evaluated by monitoring nocturnal penile tumescence and rigidity, and were classified as having normal (n = 26), irregular (dissociation, short episode or low amplitude, n = 146), or flat erectile pattern (n = 26). Exposure to environmental agents was assessed by a detailed interview, and 4 groups were constituted: nonexposed, pesticide-exposed, solvent-exposed, and heat-exposed. A multivariate polytomous logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for association between quality of nocturnal erections and exposure groups adjusted for confounding factors. Exposure to environmental agents was a risk factor for a flat erectile pattern (OR 7.1, 95% CI 1.5-33.0 for pesticides; OR 12.2, 95% CI 1.2-124.8 for solvents; and OR 1.7, 95% CI 0.3-9.4 for heat). Associations were much weaker for an irregular erectile pattern (OR 1.8, 95% CI 0.5-6.7 for pesticides; OR 2.1, 95% CI 0.3-17.9 for solvents; and OR 1.2, 95% CI 0.4-4.0 for heat). Our results suggest that environmental agents constitute a risk factor for erectile dysfunction by interfering with erectile ability.

Age Factors↗

PubMedDate not supplied

Initial validation of a novel rat model of vasculogenic erectile dysfunction with generalized atherosclerosis.

Although rats have been widely used in evaluating various causes of vasculogenic erectile dysfunction (VED), the atherosclerotic rat model has seldom been tried probably due to its inherent tolerance to a cholesterol diet. To enhance endothelial sensitivity to cholesterol diet, we tested the effects of transient interruption of nitric oxide synthase on atherogenesis induced by cholesterol diet in a rat model. Rats with atherosclerosis (AS group) received 1% cholesterol diet for 6 weeks. During the initial 2 weeks, they drank water that contained N(G)-nitro-L-arginine methyl ester (L-NAME) (3 mg/ml). After 6 weeks, we carried out histologic and hemodynamic evaluation to confirm pelvic atherosclerosis and erectile dysfunction, respectively, and the results were compared with those of cholesterol only (Chol) group and normal control (C) group. Compared to the C or Chol group, the mean intima/media (I/M) of the internal pudendal artery, which contributes approximately 70% of the total resistance of the penile vasculature, was markedly increased by the treatment (1.82+/-0.25 vs 0.77+/-0.13, P<0.05). Correspondingly, significantly diminished erectile function was observed. Combined treatment for 2 weeks elicited early atherosclerotic changes in proximal arteries and erectile impairment and further 4 weeks of cholesterol diet spread overt atherosclerosis to the periphery. The Chol group showed no arterial pathology, although they showed mild VED. A correlation study showed that atherosclerosis of the distal artery was better correlated with erectile dysfunction than the proximal artery. Based on these results, our study demonstrates that combination treatment of cholesterol diet with L-NAME would be used as a rapid, effective protocol of developing atherosclerotic rat model of VED.

Animals↗

PubMed1997

Comparison of transdermal nitroglycerin and intracavernous injection of papaverine in the treatment of erectile dysfunction in patients with spinal cord lesions.

This study was done to evaluate the effectiveness of transdermal nitroglycerin in the treatment of erectile dysfunction in males with spinal cord lesions as compared to the treatment with intracavernous injection of papaverine. The study design used was an open, randomized, cross over trial of intracavernous injection papaverine versus transdermal nitroglycerin. Twenty eight male patients with spinal cord lesions with erectile dysfunction were included in the study, and were subjected to intracavernous injection of papaverine and transdermal nitroglycerin with an interval of 2 weeks as the wash out period. Objectively, the times taken for the onset and the duration of erection were noted. The length of the penis and its circumference at its base were measured at intervals until the erection subsided. The volume of the penis at the onset and at the peak of erection was calculated. Twenty six patients (ie 93%) who received an injection of papaverine, and 17 (ie 61%) of the patients who received nitroglycerin showed a complete response. The difference was statistically significant (P = 0.004). Nine (32%) patients had complications with the injection of papaverine. The only complication noted with the application of a nitroglycerin patch was mild headache, experienced by six (21%) patients. It was concluded from the study that intracavernous injection of papaverine is more effective than transdermal nitroglycerin in the treatment of erectile dysfunction in patients with spinal cord lesions.

Administration, Cutaneous↗

PubMed2003

[Erectile dysfunction: reasonable diagnostics and treatment in general practice].

The availability of efficacious oral drugs has radically changed the diagnostic and therapeutic approach to erectile dysfunction. Complicated examinations as well as invasive treatment options have been widely abandoned. Instead the management of impotent men has become much more pragmatic and focused on the symptom. Consequently only a minority of impotent men needs to be referred to an urologist, which makes the therapy of erectile dysfunction increasingly attractive for general practitioners. However, successful treatment first of all still needs time and a genuine interest in the field of erectile dysfunction. In this article a reasonable diagnostic evaluation of impotent patients in general practice is described. Furthermore indication and use of little or non-invasive therapies are discussed.

Administration, Oral↗

PubMed1999

[Secondary erectile dysfunction. Is oral medication in the diagnostic phase indicated?].

For patients with erectile dysfunction oral medication seems to be the most comfortable form of application. This can also be seen in the expectations looking forward to Sildenafil and other drugs in development. We present a prospective examination with the oral medication of 100 mg acecarbamol, 30 mg extract of cortex quebracho and 33 mg tocopherol acetate (Afrodor) in 100 patients complaining secondary erectile dysfunction. The patients were treated unselected with 3 x 1 tablet/day during the diagnostic schedule. 14% of the patients were able to perform satisfying sexual intercourse after 4 weeks of medication and another 15% showed an increased libido. Therefore we suggest, that the application of an oral medication, might be useful, especially during the time of diagnostics. Especially for those patients who gain without invasive diagnostic tools as intracavernous injection.

Administration, Oral↗

PubMedDate not supplied

Phosphodiesterase inhibitors in the treatment of erectile dysfunction.

Based on knowledge of intracellular signal propagation in cavernous smooth muscle tone regulation and the development of new and selective pharmacological agents, selective phosphodiesterase (PDE) inhibitors were recently introduced in the treatment of erectile dysfunction. The presence of mRNAs specific for 13 different human phosphodiesterase isoenzymes and isoforms in human cavernous tissue was shown by RT-PCR. We detected an expression of the following genes encoding for both cAMP and cGMP hydrolyzing PDEs: all three isogenes of PDE I and PDE IIa, which do hydrolyze cAMP as well as cGMP; the specific cAMP hydrolyzing PDEs PDE IIIa, the four isogenes of PDE IV, PDE VIIa and PDE VIIIa and the cGMP-specific PDEs PDE Va and PDE IXa. By protein chemical methods, PDE-isoenzymes III, IV and V were characterized in the human cavernous smooth muscles. In functional organ bath studies using precontracted human cavernous tissue strips, PDE III and V inhibitors showed the most pronounced relaxant responses. In clinical studies, the use of the orally active PDE V inhibitor sildenafil induced a pronounced and significant erectogenic effect in patients both with predominantly psychogenic and organogenic etiology of erectile dysfunction. The first promising clinical data of the use of an orally active PDE inhibitor for the treatment of erectile dysfunction are well supported by consistent basic scientific findings. Further research will possibly allow to identify diagnostic tools for erectile dysfunction and for even more selective drugs in its therapy.

Journal Article↗

PubMedDate not supplied

[Sildenafil citrate in diagnosis of erectile dysfunction].

We examined 86 patients: 24 with functional and 62 with organic erectile dysfunction (EDF). In functional EDF, sildenafil citrate (SC) in a dose 25-50 mg or intracavernous injection of 2% solution of papaverin always resulted in satisfactory erection. In EDF, SC, papaverin injection and LOD test results were compared. Morphological examinations of cavernous tissue and tunical albuginea of the penis. Correlations were found between clinical findings, results of SC and intracavernous papaverin solution administration, LOD-test, morphological evidence. This provides objective data for classification of EDF into three stages (I, II and III). Stages I and II were defined as compensated, stage III--as a decompensated stage of organic erectile dysfunction. SC has some advantages over other tests, therefore it is recommended as a monomethod for diagnosis of functional forms, indirect staging of organic EDF.

Erectile Dysfunction↗

PubMed1996

The correlation between the new RigiScan plus software and the final diagnosis in the evaluation of erectile dysfunction.

PURPOSE: The computer generated recordings for 2 nights in 40 patients studied with the RigiScan device were reevaluated using the new RigiScan Plus software to test its value in improving the discrimination between psychogenic and organic erectile dysfunction. MATERIALS AND METHODS: Each man was evaluated for erectile dysfunction with a detailed medical and sexual history, physical examination, biothesiometry, plethysmography, 2 nights of ambulatory RigiScan monitoring and a psychological evaluation that usually included a private interview with the sexual partner. At the conclusion of evaluation each patient was broadly classified as having organic or psychogenic erectile dysfunction. The RigiScan reports were initially independently analyzed without the investigator's knowledge of the final diagnosis by determining the single best erectile event, with a minimal cutoff value of 60% erection for 5 minutes as necessary to be considered normal and the sum of measurements from the 2 nights. The original reading and final diagnosis were correlated. At this point the data were processed with the new RigiScan Plus software using 2 new measurements: 1) rigidity activity units and 2) tumescence activity units at the base and tip of the penis, and the results were correlated with the final diagnosis. RESULTS: Evaluation of the single best event again showed that tip rigidity was the best single predictor if the diagnostic criteria were modified to 70% tip rigidity for 5 minutes with an estimate of correct classification of 92.5%. Nearly the same accuracy was obtained by base single event rigidity, tip rigidity and base tumescence activity units (each 90%). The summary analysis of all erectile events during the 2 nights of evaluation that had a low correlation with the final diagnosis using the original software showed that the best overall predictor of final diagnosis was tip tumescence activity units (92.5%), followed by base rigidity and tumescence activity units (each 90%). CONCLUSIONS: The RigiScan Plus software introduced 4 new parameters that facilitate interpretation of the RigiScan data. The new software did not improve the correlation with the final diagnosis compared to the subjective single best event analysis but added new objective parameters, measured and displayed by the software, that facilitate use of the data by the physician.

Diagnosis, Differential↗

PubMed2001

Sildenafil citrate for the treatment of erectile dysfunction in men with Type II diabetes mellitus.

AIMS/HYPOTHESIS: Ninety percent of all men with diabetes have Type II (non-insulin-dependent) diabetes mellitus, and erectile dysfunction (ED) is common in this patient group. This study evaluated the effects of sildenafil on men with erectile dysfunction and Type II diabetes and compared the results with glycated haemoglobin concentrations and chronic diabetic complications. METHODS: Patients (mean age, 59 years) in this double-blind, placebo-controlled trial were randomised to sildenafil (25-100 mg; n = 110) or matching placebo (n = 109) for 12 weeks. Primary criteria for efficacy included questions 3 (achieving an erection) and 4 (maintaining an erection) from the International Index of Erectile Function (IIEF, score range, 0-5). Secondary outcome measures included a global efficacy question (GEQ), patient event logs, a life satisfaction checklist, and the remaining IIEF questions. RESULTS: After 12 weeks, the mean scores for questions 3 and 4 had improved significantly in patients receiving sildenafil (3.42 +/- 0.23 and 3.35 +/- 0.24) compared with placebo (1.86 +/- 0.22 and 1.84 +/- 0.23; p < 0.0001). Similarly, the GEQ score was higher in the sildenafil (64.6 %) than the placebo group (10.5 %). Even when correlating efficacy with glycated haemoglobin concentrations ( < or = 8.3 % or > 8.3 %, the median concentration found in this study) or the number of diabetic complications (0 or > or = 1), the mean scores for the GEQ and questions 3 and 4 from the IIEF remained higher for all the sildenafil groups compared with the placebo groups (p < 0.0001). CONCLUSION/INTERPRETATION: Sildenafil was well-tolerated and effective in improving erectile dysfunction in men with Type II diabetes, even in patients with poor glycaemic control and chronic complications.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1998

[The relationship of cavernous oxygen tension with erectile dysfunction of vascular origin].

OBJECTIVE: To determine the intracavernous partial oxygen pressure in different etiological groups of erectile dysfunction: psychogenic (control group), arterial and veno-occlusive and the value of intracavernous gasometry as an indicator of the degree of severity of impotence. METHODS: A total of 16 patients were evaluated according to the diagnostic protocol utilized to determine the etiology of erectile dysfunction. Intracavernous blood samples were obtained during the initial phase of gasometry and PO2 was determined by standard gasometric methods. RESULTS: After injection of the vasoactive drug, the mean intracavernous PO2 was 92.4 +/- 1.27 for the control group, 62.2 +/- 0.85 for the group with arterial impotence, and 76.8 +/- 1.45 for the group with venous impotence, demonstrating a statistically significant difference (p < 0.01). CONCLUSIONS: Intracavernous gasometry, in combination with other diagnostic tests, is useful for evaluating the degree of severity of erectile dysfunction. The reduction in cavernous oxygen tension, which induces cavernous tissue fibrosis, can be considered to be a common mechanism in arterial and venous impotence.

Adult↗

PubMed2003

Appropriate use of exercise testing prior to administration of drugs for treatment of erectile dysfunction.

Selective inhibitors of phosphodiesterase type 5 prevent the breakdown of cyclic guanosine monophosphate resulting in enhanced penile erection and are used for the treatment of erectile dysfunction. Those agents, by way of vasodilator effects could interact with the systemic vasculature and could potentially affect the cardiac patient. During sexual intercourse, heart rate and blood pressure increase as with other forms of exertion. Stress to the heart during sexual intercourse is similar than that observed during other common daily activities. This article reviews the literature and provides recommendations regarding the evaluation of patients with known or suspected cardiac disease in whom therapy for erectile dysfunction is being considered. Patients who seek therapy for erectile dysfunction should undergo to individualized medical evaluation before a prescription is issued. Patients requiring therapy with long-acting nitrates should not receive prescriptions for phosphodiesterase inhibitors. Patients who are likely to develop angina with sexual exertion should not take phosphodiesterase inhibitors, as they may be tempted to take sublingual nitroglycerin. Stress testing is indicated if exercise capacity is uncertain or if significant myocardial ischemia is suspected.

Clinical Trials as Topic↗

PubMed2006

Could a rural lifestyle decrease the prevalence of erectile dysfunction?

OBJECTIVE: To determine the prevalence of erectile dysfunction (ED) in a specific population and explore potential correlates with lifestyle. SUBJECTS AND METHODS: This prospective observational study, covering a population of a very small rural town, included 2000 men aged > or = 20 years from a total population of 121 831 (51% female and 49% male). The International Index of Erectile Function was completed by each of the 2000 men at their homes over a 1-year period. Another questionnaire assessing socio-economic status and health-related determinants of ED were also completed. RESULTS: All 2000 men completed the questionnaires; overall, only 34 reported ED (1.7%). The frequency of mild, mild to moderate, moderate and severe ED was 12%, 29%, 20% and 38%, respectively. Significantly more men aged > 51 years had ED than those aged <41 years (0.05% and 0.45%, respectively; P < 0.001). There was no difference in ED with salary levels. CONCLUSION: The prevalence of ED in this particular rural population of Brazil was very low, at only 1.7%. Although ED increases with age, this association was not apparent for all age groups. It seems that several others factors, e.g. lifestyle, culture and diet, could be important for the onset of ED.

Adult↗

PubMed2006

[Different questionnaires (EDITS and SLQQ) for assessing of erectile dysfunction therapy].

There are a number of scales available for evaluating treatments of erectile dysfunction. Since each differs from the other in the formulating process, component items, etc, the results of evaluation may mean different things. This paper makes a comparison of the component items and clinical application of Erectile Dysfunction Inventory of Treatment Satisfaction Questionnaire (EDITS) and Sexual Life Quality Questionnaire (SLQQ).

Erectile Dysfunction↗

PubMed2003

Review of tadalafil in the treatment of erectile dysfunction.

Approximately 150 million men worldwide experience erectile dysfunction (ED) whereby they are unable to achieve and maintain an erection adequate for satisfactory sexual performance. ED has a considerable impact on quality of life. Tadalafil (Cialis( trade mark ), Eli Lilly & Co./ICOS) is a novel effective and safe phosphodiesterase type 5 inhibitor, a secondary messenger for the smooth muscle relaxing effects of nitric oxide, which plays a central role in the vasodilation of erectile tissues. It has a longer half-life than sildenafil. As head-to-head comparative trials are lacking, it is not clear what tadalafil offers over sildenafil. In terms of marketing, much is made of the 'spontaneity' achievable because of the (relatively) longer half-life of tadalafil.

Aged↗