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Androgens and penile erection: evidence for a direct relationship between free testosterone and cavernous vasodilation in men with erectile dysfunction.

OBJECTIVE: Androgens are essential in the maintenance of nitric oxide-mediated erectile activity in the rat. The objective of the present study was to investigate the role of androgens in regulating trabecular smooth muscle relaxation in the corpus cavernosum in response to vasoactive challenge in men with erectile dysfunction (ED). DESIGN: Retrospective, double-blind correlation analyses. PATIENTS: Fifty-two impotent patients without confounding risk factors for ED were obtained from a total of 250 undergoing diagnostic evaluation. MEASUREMENTS: All patients had dynamic colour duplex ultrasound (D-CDU) and hormonal evaluation for LH, total and free testosterone, SHBG and oestradiol. RESULTS: Based upon D-CDU results patients were diagnosed as having arteriogenic (AR, n = 18; mean age 51) or corporeal venocclusive (CVO, n = 13; mean age 49) ED; in other patients (n = 21, mean age 43) a diagnosis of psychogenic (P)-ED was made by comprehensive psychogenic testing and confirmed by normal D-CDU results. AR and CVO patients had altered compliance of cavernous arteries recorded by D-CDU [20-25% lower resistive index (RI) than patients with psychogenic ED], and lower free testosterone (FT) levels than psychogenic patients [42.3 +/-3.5 SE and 49.3+/-5.2 vs. 75.2+/-7.6 pmol/l, respectively; P<0.01]. More important, in all patients there was a strong direct correlation between resistive index values and FT levels (r = 0.47, P = 0.002); the relationship was maintained also when adjusted for age, SHBG and oestradiol (r = 0.37, P = 0.02). CONCLUSIONS: These results indicate that in men with erectile dysfunction low free testosterone may correlate independently of age with the impaired relaxation of cavernous endothelial and corporeal smooth muscle cells to a vasoactive challenge. These findings give clinical support to the experimental knowledge of the importance of androgens in regulating smooth muscle function in the penis.

Cross-Sectional Studies↗

Update on erectile dysfunction in prostate cancer patients.

PURPOSE OF REVIEW: Evolution in the management of prostate cancer includes increased attention being paid to patient quality of life after treatment, specifically with issues related to sexual function. Erectile dysfunction is one of the major concerns of patients undergoing treatment for prostate cancer. There are several recognized factors that determine the postoperative incidence of erectile difficulties, including patient age, degree of cavernosal nerve sparing during surgery, cancer stage, and associated vascular comorbidities. Early initiation of rehabilitation protocols after radical prostatectomy has been advocated to promote the speed and degree of recovery of erectile function. The aim of this communication is to review recent initiatives in erectile dysfunction restoration after prostate cancer therapy. RECENT FINDINGS: In recognition of the neurogenic basis of erectile dysfunction after radical prostatectomy, new strategies have been devised to initiate the rehabilitation process. Type 5 phosphodiesterase inhibitors, vacuum erection devices, and intracavernosal and intraurethral application of vasoactive agents have all been reported in a positive light in recent studies. Developments in cavernous nerve graft interposition procedures, perioperative neuroprotection measures, and postoperative neurotrophic treatments aim to preserve prostate cancer patients' qualities of life. SUMMARY: Data generated from a number of clinical investigations document that pharmacologic rehabilitation programs provide a higher rate of recovery of erectile function following radical prostatectomy. Both intracavernosal and intraurethral applications of vasoactive agents and vacuum devices can speed the recovery period for return of erectile function. Various neuroprotective and neurotrophic approaches are thought to provide integral roles for the maintenance of sexual function in men undergoing prostate cancer therapy.

Animals↗

Topical prostaglandin E1 SEPA gel for the treatment of erectile dysfunction.

PURPOSE: We compare the systemic effects, local tolerance and effectiveness of topical gel formulations on the penis containing alprostadil (prostaglandin E1) plus 5% SEPA versus SEPA alone (placebo) in men with erectile dysfunction. MATERIALS AND METHODS: Erectile response, skin discomfort and erythema were measured in 48 men with erectile dysfunction secondary to vascular, neurogenic, psychogenic or mixed etiologies in this single-blind, placebo controlled trial. RESULTS: Application of prostaglandin E1 gel correlated positively with erectile response as 67 to 75% of patients had an erection compared to 17% of controls (p<0.001). Blood pressure and heart rate varied minimally. No serious adverse effects were observed in the 48 patients, although the majority had skin discomfort. CONCLUSIONS: Topical prostaglandin E1 gel applied to the penis appears to be safe, and facilitates audiovisual and tactile stimulation resulting in an erection when given in a clinic setting. Consequences to the female partner remain unknown.

Adjuvants, Pharmaceutic↗

Erectile dysfunction. A guide to diagnosis and management.

BACKGROUND: Erectile dysfunction (ED) is a common age related problem best managed in general practice. The incidence of ED will thus increase as men live longer. It is only in the past decade that the pathophysiology of ED has been well understood. OBJECTIVE: This article discusses the mechanisms of normal erectile function and dysfunction and the assessment and management of ED. DISCUSSION: The success of currently available and newly emerging oral agents has revolutionised the management of ED. However, the majority of men with ED remain undiagnosed and untreated and patients are often unable to distinguish between a problem of ED, desire or libido. It is particularly important for general practitioners to enquire about ED in middle aged and older men, diabetics and patients with vascular disease. Appropriate management goes beyond management of the actual condition, and involves addressing lifestyle and psychosocial issues.

Adult↗

Complications associated with the use of vacuum constriction devices for erectile dysfunction in the spinal cord injured population.

The vacuum constriction device has generally been regarded as a safe and effective alternative to pharmacologic intracorporal injections or surgical placement of a penile prosthesis for the treatment of erectile dysfunction. This paper serves to exemplify the potential complications of the device when used to treat erectile dysfunction in the spinal cord-injured (SCI) population. Two cases of subcutaneous penile hemorrhage in patients using anticoagulant therapy (one treated with subcutaneous heparin and one with coumadin) and one case of penile gangrene occurred in three different SCI males. Physicians managing erectile dysfunction in SCI patients should be aware of these potential serious morbidities. The management and means of prevention of these complications are presented.

Adult↗

Evaluating the relationship between erectile dysfunction and dose received by the penile bulb: using data from a randomised controlled trial of conformal radiotherapy in prostate cancer (MRC RT01, ISRCTN47772397).

AIM: To evaluate the relationship between erectile function and the radiation dose to the penile bulb and other proximal penile structures in men receiving conformal radiotherapy (CFRT) for prostate cancer (PCa). METHODS: The Medical Research Council (MRC) RT01 trial randomised 843 men who had localised PCa to receive either 64 or 74 Gy after 3 - 6 months neoadjuvant hormonal treatment. Fifty-one men were selected who were potent prior to hormonal treatment, having completed both pre-hormone and 2-year post-CFRT Quality of Life assessments, and on whom dose volume data were available for analysis. The men were divided into three groups according to 2-year follow-up: potent, reduced potency, and impotent. The bulb of the penis together with the crura, were outlined on restored treatment plans. Dose - volume histograms were generated and compared between the three groups. An ordered logistic regression model was used to calculate the odds ratio of a range of dose - volume parameters to the penile bulb and effect on erectile dysfunction. The dose to the penile bulb was correlated to the dose received by the crura. RESULTS: Of the 51 patients, 12 remained potent, 22 had reduced potency, and 17 were impotent at 2 years. No differences were seen in mean dose to the penile bulb by allocated treatment (t test = 1.61, p = 0.11). The mean doses to the penile bulb received by the potent, reduced potency, and impotent groups were 45.5 Gy (SD 17.1), 48 Gy (SD 16.1), and 59.2 Gy (SD 13.8), respectively. There was a strong correlation between the mean dose received by the penile bulb and dose to the crura (r = 0.82, p < 0.0001). 83.3% of impotent patients received a D90 > or = 50 Gy to the penile bulb compared with 29.4% of patients who maintained potency at 2 years (p = 0.006). CONCLUSION: There is evidence from this study to suggest a dose volume effect on the penile bulb and erectile dysfunction. A D90 > or = 50 Gy is associated with a significant risk of erectile dysfunction and this should form a basis for selecting dose constraints in future dose escalation studies.

Adenocarcinoma↗

Efficacy, safety and predictive factors of therapeutic success with sildenafil for erectile dysfunction in patients with different spinal cord injuries.

STUDY DESIGN: Multicenter, open, prospective, before-after study. OBJECTIVE: To assess the efficacy and safety of sildenafil therapy for erectile dysfunction in patients with spinal cord injury, and the association between the response to sildenafil and factors such as causes and levels of spinal cord injury, grade of ASIA deficit, time since injury, orgasmic perception, and degree of baseline erection. SETTING: Homes of outpatients of 16 spinal cord injury units in Spain. METHOD: One hundred and seventy patients with erectile dysfunction secondary to spinal cord injury, from whom baseline data were collected on their sexual function, and who started treatment with sildenafil 50 mg. An efficacy assessment was made by the patient and his partner, and the score of the International Index of Erectile Function (IIEF) was recorded. RESULTS: It was reported by 88.2% of the patients and 85.3% of their partners that treatment with sildenafil had improved their erections, regardless of the baseline characteristics of the spinal cord injury and erectile function. In responders, this improvement was confirmed by an increase from 12.5 to 24.8 points (P<0.001) of the Erectile Function Domain of IIEF. A significant improvement was also seen in patients' satisfaction with sexual activity and general satisfaction derived from sexual life. Preservation of orgasmic perception and a baseline degree of erection of 3 or 4 (P=0.006) were predictors of therapeutic success. No serious adverse events occurred. CONCLUSION: Sildenafil is an effective, well-tolerated treatment for erectile dysfunction caused by spinal cord injury, regardless of the cause, neurological level, ASIA grade, and time since injury. SPONSORSHIP: Spanish Society of Paraplegia.

Adult↗

[Provocation of corpus cavernosum EMG signals as a parameter in diagnosis of erectile dysfunction].

Parameters of CC-EMG able to distingiush between healthy controls and men with erectile dysfunction of different etiology in the individual case are currently unknown. Groups of healthy volunteers and men with erectile dysfunction however show significant differences in provocability of slow cavernous electric activity, i.e. if so called "typical single potentials" (tSP) can be recorded already under resting conditions, or only with provocation, or if any activity is missing. In men, who showed tSP already under resting conditions, a significantly higher extent of provoked activity could be assessed as in those, who showed tSP only after provocation. This applies to the number as well as for the extent of the responses to the 3 stimuli valsalva-manoeuvre, arousal and hyperventilation. Patients, who had shown tSP already under resting conditions, were similar to the controls, from whom those, who showed tSP exclusively with provocation differed significantly. Further research will have to prove, if the parameter "provocability" together with the parameter "extent of the provoked cavernous electric activity" might be able to to lead to a better distinction of healthy and pathological situations which would be a precondition for the introduction of the method into clinical use.

Adult↗

Efficacy of sildenafil citrate in treatment of erectile dysfunction: effect of type 2 diabetes.

PURPOSE: To assess efficacy of sildenafil citrate in treatment of erectile dysfunction: effect of type 2 diabetes. MATERIALS AND METHODS: A total of 466 male patients with erectile dysfunction (ED) were enrolled in this study. Of them 382 were diabetic and 84 were non-diabetic. Patients were screened for ED using the erectile function domain of the International Index for Erectile Function (IIEF). Patients underwent routine laboratory investigations, in addition to total testosterone and prolactin assessment. To assess the effect of diabetes on efficacy of sildenafil, we compared the pre and post sildenafil responses to erectile function domain, Q3, Q4. Overall satisfaction and global efficacy question (GEQ) were also assessed. RESULTS: Mean age +/- S.D. was 53 +/- 8.4 and 49.7 +/- 10.6 years for patients with and without diabetes respectively. There were significant associations between increased severity of ED and longer duration, poor metabolic control and presence of more than one diabetes-related complication (p < 0.05 for each). Differences were significant between pre and post sildenafil administration regarding erectile function domain, Q3, Q4 (p < 0.05 for each). In the non-diabetic patients the GEQ and the overall satisfaction were significantly higher than in diabetics (p < 0.05 for each). Global efficacy question was significantly low in patients with fair and poor metabolic control, longer duration of diabetes, and patients with diabetic complications (p < 0.05 for each). CONCLUSIONS: Sildenafil is an effective treatment for diabetic patients with ED. Although the efficacy of sildenafil was negatively affected by factors as poor control and longer duration of diabetes and presence of more than one diabetes-related complication, however, the global efficacy and the overall patients' satisfaction were high.

Analysis of Variance↗

Prevalence of sleep apnea in men with erectile dysfunction.

Sleep studies were performed on 1,025 patients complaining of erectile dysfunction. In addition to standard measures of sleep stage and nocturnal penile tumescence, respiratory activity was evaluated. The number of episodes of sleep apnea per hour (Apnea Index--AI) was calculated for each patient. The overall prevalence of sleep apnea activity in this sample was: 43.8 percent with AI greater than or equal to 5; 27.9 percent with AI greater than or equal to 10; and 19.6 percent with AI greater than or equal to 15. These results confirm that sleep apnea activity is common in men with erectile dysfunction. This high prevalence also indicates that further study is needed to elucidate pathophysiology of erectile failure in men with sleep apnea.

Adult↗

High prevalence of erectile dysfunction after renal transplantation.

BACKGROUND AND METHODS: A cross-sectional study of multifaceted male sexual function in 323 consecutive kidney transplant recipients was conducted by mail by means of the validated International Index of Erectile Function (IIEF). All five IIEF domains (IIEF-5), i.e., erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction, were scored for each responder. IIEF-5 scoring that conformed to the National Institutes of Health definition of erectile dysfunction (ED) was computed for all patients sexually active within the past 4 weeks. RESULTS: Two hundred and seventy-one patients replied. Compared to the controls used for IIEF psychometric validation, kidney transplant recipients gave lower erectile function (P<0.01) and intercourse satisfaction (P<0.05) scores, despite their being younger. ED, according to the IIEF-5 method, was demonstrated in 55.7% of the sexually active patients (n=212). Age, time on dialysis, and iterative transplants were significantly and negatively related to erectile dysfunction. CONCLUSION: IIEF proved to be a valuable means of unveiling highly prevalent erectile dysfunction in male kidney transplant recipients. The negative impact of the time on dialysis was emphasized in the results.

Adult↗

Missed testicular torsion presenting with male infertility and erectile dysfunction.

Testicular torsion has been estimated to affect 1 in every 4 000 males younger than the age of 25 years and has peaks of incidence occurring in the neonate and the adolescent entering puberty. The incidence of missed testicular torsion was about was 4%. The incidence of missed non-simultaneous bilateral torsion was unknown. We presented a case of missed bilateral testicular torsion with resulting primary testicular failure and hypogonadism with erectile dysfunction. The patient was seen for infertility and erectile dysfunction 10 years after the testicular torsion. Semen analysis revealed azoospermia. Serum total testosterone was at the castration level (0.14 nmol/L). His infertility was irreversible. His erectile dysfunction was managed successfully with testosterone replacement and use of sildenafil.

Adult↗

Erectile dysfunction.

A better understanding of penile physiology and pathophysiology has revolutionized the diagnosis and treatment of erectile dysfunction in the past decade. This article summarizes the current knowledge and presents a patient's goal-directed approach to the evaluation and treatment of erectile dysfunction.

Erectile Dysfunction↗

Infusion pharmacocavernosometry and nocturnal penile tumescence findings in men with erectile dysfunction.

Infusion pharmacocavernosometry and nocturnal penile tumescence findings were compared in 50 men with erectile dysfunction of either organic or psychogenic etiology. Of the men 29 had abnormal and 21 had normal nocturnal penile tumescence. Infusion pharmacocavernosometry parameters (equilibrium pressure, maintenance flow rate and 30-second pressure fall) were compared to nocturnal penile tumescence status (normal versus abnormal). When traditional normal values were used for infusion pharmacocavernosometry parameters poor correlation with nocturnal penile tumescence status was found. When new cutpoints for infusion pharmacocavernosometry parameters were chosen a stronger correlation was noted. This study suggests that when vasoactive drugs are injected intracavernously for diagnostic purposes, anxiety and/or the absence of sexual stimulation following the injection may prevent complete cavernous smooth muscle relaxation resulting in falsely abnormal values. Therefore, over reliance on infusion pharmacocavernosometry as a single test for evaluation and treatment decisions concerning erectile dysfunction should be avoided.

Adult↗

Erectile dysfunction in chronic peritoneal dialysis patients: incidence and treatment with sildenafil.

OBJECTIVES: Sexual and erectile dysfunction (ED) have been reported to occur frequently in male patients with end-stage renal disease maintained on dialysis. Numerous etiologies for this ED have been suggested. Although a variety of therapies for the ED of the dialysis patient have been suggested, most clinicians indicate that patients report a poor response to therapy. Recently, sildenafil has been reported to be beneficial in treating patients with ED of both organic and psychogenic causes. The present study was designed to document the incidence of ED in male patients maintained on chronic peritoneal dialysis (CPD) and to determine the efficacy of prescribing sildenafil therapy to treat their ED. METHODS: All male patients in our CPD unit were notified by letter of the availability of sildenafil as a treatment modality for ED. A sexuality/erectile dysfunction assessment was conducted in all male patients by their primary nephrologist. Patients who reported ED and who had no medical contraindication to sildenafil were offered this therapy. Those patients who were interested in this treatment were interviewed by a social worker, and patients were asked to complete the International Index of Erectile Function questionnaire. Sildenafil was prescribed at a starting dose of 25 mg and increased to a maximum of 100 mg during a 12-week study trial. Patients were re-evaluated 6 and 12 weeks after the start of therapy. RESULTS: There were 68 male patients maintained on CPD at the time of the study. Mean age of all patients was 60.8 +/- 15.3 years and mean duration on PD was 32.6 +/- 25.6 months. Thirty-three patients had diabetes, 66 hypertension, 35 peripheral vascular disease, and 32 coronary artery disease. Thirty-two of 68 male patients in the CPD unit were assessed to have ED. Only 17 of the 32 patients expressed interest in pursuing sildenafil therapy. Two of these patients were excluded because they were receiving nitrate therapy. Of the 15 patients who agreed to take sildenafil, only 6 completed the 12-week study. Two of these patients responded to sildenafil. CONCLUSION: Erectile dysfunction is common in male patients maintained on CPD. Only about half of patients with ED in the present study were willing to consider sildenafil therapy to treat the ED and, of those who agreed to treatment, only a minority completed the 12-week trial; 2 of these 6 patients reported a satisfactory response.

Erectile Dysfunction↗

Sildenafil, a novel effective oral therapy for male erectile dysfunction.

OBJECTIVES: To determine the efficacy and safety of sildenafil, a novel orally active inhibitor of the type-V cyclic guanosine monophosphate-specific phosphodiesterase (the predominant isoenzyme in the human corpus cavernosum) on penile erectile activity in patients with male erectile dysfunction of no established organic cause. PATIENTS AND METHODS: Twelve patients (aged 36-63 years) with male erectile dysfunction of no established organic cause were entered into a double-blind, randomized, placebo-controlled, crossover study which was conducted in two phases. In the first phase (four-way crossover), treatment efficacy was evaluated by measurements of penile rigidity using penile plethysmography during visual sexual stimulation at different doses of sildenafil (10, 25 and 50 mg or placebo). In the second phase (two-way crossover), efficacy was assessed by a diary record of penile erectile activity after single daily doses of sildenafil (25 mg) or placebo for 7 days. RESULTS: The mean (95% confidence interval, CI) duration of rigidity of > 80% at the base of the penis was 1.3 min (0.4-3.1) in patients on placebo, 3.5 min (1.6-7.3; P = 0.009) on 10 mg, 8.0 min (3.7-16.7; P = 0.003) on 25 mg and 11.2 min (5.6-22.3; P < 0.001) on 50 mg of sildenafil. The mean (95% CI) duration of rigidity of > 80% at the tip of the penis was 1.2 min (0.4-2.7) on placebo and 7.4 min (2.4-8.5; P = 0.001) on 50 mg sildenafil. From the diary record of daily erectile activity, the mean (95% CI) total number of erections was significantly higher in patients receiving sildenafil was 6.1 (3.2-11.4), compared with 1.3 (0.5-2.7) in those on placebo; 10 of 12 patients reported improved erectile activity while receiving sildenafil, compared with two of 12 on placebo (P = 0.018). Six patients on active treatment and five on placebo reported mild and transient adverse events which included headache, dyspepsia and pelvic musculo-skeletal pain. CONCLUSION: These results show that sildenafil is a well tolerated and effective oral therapy for male erectile dysfunction with no established organic cause and may represent a new class of peripherally acting drug for the treatment of this condition.

3',5'-Cyclic-GMP Phosphodiesterases↗

Prostaglandin E1 versus linsidomine chlorhydrate in erectile dysfunction.

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 linsidomine chlorhydrate (SIN-1) in patients with erectile dysfunction have had conflicting results. We performed a single-blind cross-over trial in 20 patients with erectile dysfunction of mixed etiology comparing prostaglandin E1 (PGE1) to SIN-1 at two different dosages (1 and 2 mg, respectively) in order to determine the effectiveness of SIN-1. PGE1 always achieved the best response, SIN-1 performed statistically significantly poorer irrespective of the dosage used. There were only a few side effects with no significant difference. SIN-1 is not a useful alternative to PGE1 in the treatment of erectile dysfunction.

Adult↗