Type 5 phosphodiesterase inhibitors: curing erectile dysfunction.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
Wayne J G Hellstrom
Publications and source records attributed to Wayne J G Hellstrom.
Semen and sperm reference ranges for men 45 years of age and older.
The most widely used reference values for human semen and sperm variables were developed by the World Health Organization (WHO) to help assess the fertility status of men interested in reproduction (typically a younger population). In this retrospective analysis, data from a large population of men aged 45 years or older were analyzed to derive semen and sperm reference ranges for an older population. Baseline semen samples were obtained from 1174 men with no or mild erectile dysfunction (ED) during the screening phase of two clinical trials evaluating the effects of a drug on human spermatogenesis. The median values and 95% reference ranges for 4 measured semen and sperm parameters (semen volume, sperm concentration, sperm motility, and sperm morphology) and 1 derived parameter (total sperm count) were calculated for the population and by age quartile. These references ranges were compared to established WHO reference values. Associations between the semen and sperm parameters and smoking status, alcohol use, and serum hormone concentrations were also analyzed. The mean age was 52.9 years (range: 45-80). Median semen volume, sperm motility, and sperm morphology parameters declined significantly with age. Only 46% of study subjects had baseline values for semen and sperm parameters that met or surpassed all the WHO reference values. This is the first study to statistically derive semen reference ranges from a large population of men aged 45 years or older. The observation that less than half the men in this study met all 4 WHO reference values for measured semen and sperm parameters underscores the need for age-specific reference ranges.
Aging↗
Visual field defect and intracerebral hemorrhage associated with use of vardenafil (Levitra).
Explore the source record for details and available documents.
Aged↗
Synchronous prosthetic implantation through a transscrotal incision: an outcome analysis.
PURPOSE: The ease of the transscrotal approach for penile prosthesis implantation and the proximity of the urethra has allowed the evolution of a new strategy for dual implantation of an AUS and IPP at a single setting. Concerns regarding increased infection rates and poor outcomes have prevented widespread acceptance of this simultaneous implantation technique. A multi-institutional evaluation of dual prosthesis implantation was performed to determine the overall efficacy, safety and long-term success of this innovative approach. MATERIALS AND METHODS: We performed a multi-institutional, retrospective analysis in patients with 2 urological prostheses (AUS and IPP). Only patients undergoing dual implantation via a single transscrotal technique were included for evaluation. Comorbidities, infection rates, and intraoperative and postoperative complications were recorded. RESULTS: A total of 22 men underwent AUS and IPP device implantation between 2000 and 2003 in a synchronous manner. Mean followup was 17 months. Complications were urethral erosion in 2 patients (9%) and reservoir migration in 2 (9%), of whom 1 underwent revision. Importantly no patient experienced a prosthetic infection postoperatively. The overall revision rate was 14%, due to urethral erosion of the AUS in 2 patients and reservoir migration in 1. All patients reported urinary leakage requiring 1 pad daily or less. CONCLUSIONS: Our initial intermediate followup in patients who underwent synchronous dual prosthetic implantation was favorable. The inherent advantage of a single anesthetic event and a single transscrotal incision should encourage widespread acceptance of this technique.
Aged↗
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↗
Antisperm antibodies and varicocele.
Explore the source record for details and available documents.
Autoantibodies↗
The breakdown of preformed advanced glycation end products reverses erectile dysfunction in streptozotocin-induced diabetic rats: preventive versus curative treatment.
OBJECTIVES: Accumulation of advanced glycation end products (AGEs) has been linked to many of the complications of diabetes mellitus, including erectile dysfunction (ED). Furthermore, it has been demonstrated that inhibitors of AGE formation, such as aminoguanidine, can prevent ED in diabetic animals. However, it is unknown whether late administration of a putative cross-link breaker, ALT-711, can reverse diabetic ED. We therefore compared ALT-711 and aminoguanidine in their ability to reverse ED in diabetic rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomly divided into four groups: (i) age-matched controls; (ii) streptozotocin (STZ)-induced diabetic rats (60 mg/kg; intraperitoneal injection); (iii) STZ diabetic rats treated with ALT-711 (3 mg/kg/day, intraperitoneal injection); and (iv) STZ diabetic rats treated with aminoguanidine (1 gm/L in drinking water) during the final 6 weeks of 12 weeks of induced diabetes. At the end of 12 weeks, erectile response to cavernous nerve stimulation (CNS) was determined. Neuronal nitric oxide synthase (nNOS) contents were measured in all penises, and AGE levels were determined both in penile tissues and in serum samples. RESULTS: Erectile responses to CNS and penile nNOS protein content were significantly reduced, while AGE levels were elevated in the penises and serum of untreated diabetic animals. Treatment with ALT-711, but not with aminoguanidine, reversed ED and nNOS depletion and reduced serum and penile tissue AGE levels. CONCLUSIONS: These results suggest that cross-link breakers, such as ALT-711, are the optimal therapeutic approach, compared with treatment with inhibitors of AGE formation, in the reversal of diabetes-related ED.
Animals↗
The impact of vascular risk factors on erectile function.
The main cause of erectile dysfunction is organic in nature, with vascular etiologies being the most common risk factors. The incidence of erectile dysfunction increases with the number of vascular comorbidities such as hypertension, diabetes, hyperlipidemia, smoking and atherosclerosis. The earliest signal of endothelial damage in men with vascular risk factors is the manifestation of erectile dysfunction. The penis is a barometer of the body's endothelial function, so it is reasonable then to correlate vascular pathologies as direct causes of erectile dysfunction. Moreover, erectile dysfunction may be the first clinical presentation of any of these comorbidities, with the vascular endothelium playing a pivotal role in regulating vascular homeostasis of the corpora cavernosa. This article addresses the impact of vascular risk factors on erectile function based on current evidence.
Diabetes Mellitus↗
Central nervous system agents in the treatment of erectile dysfunction.
In the last two decades, a better understanding of the mechanisms governing erectile function and the pathophysiologies underlying erectile dysfunction (ED) have led re-searchers to investigate novel treatment concepts. Selective type-5 phosphodiesterase inhibitors are recommended as first-line therapy because of their high efficacy, but 30% to 40% of patients who have ED do not respond adequately to these agents and require alternative methods. The central nervous system plays a fundamental role in sexual behavior. Animal models have advanced our understanding of the neuroanatomic and neuropharmacologic basis of centrally induced penile erections. Clinical research with apomorphine has demonstrated efficacy in men who have a range of ED. Recent interest has focused on other centrally acting agents for ED treatment, including the melanocortin receptor agonists.
Apomorphine↗
The relationship between the type of penile abnormality and penile vascular status in patients with peyronie's disease.
PURPOSE: We evaluated penile vascular status using penile duplex Doppler ultrasound (PDDU) according to the type of abnormality in men with Peyronie's disease (PD). MATERIALS AND METHODS: A total of 523 patients with PD were evaluated retrospectively. Each patient underwent PDDU following injections of 10 to 15 mug prostaglandin E1 intracavernously with accompanying visual sexual stimulation to evaluate penile blood flow. Abnormalities were divided into 7 groups. Objective evaluation of penile curvature was done with a protractor during maximum erection. Specific criteria were used to categorize patients into varying definitions of vascular status. The results were compared statistically among groups. RESULTS: Mean patient age +/- SEM was 54.2 +/- 1.5 years. The most frequently noted type of curvature was dorsal (43.5% of cases), followed by lateral (24.8%). Mean peak systolic velocity in the ventrolateral group was the highest, while the lowest peak systolic velocity was noted in the hourglass abnormality group. The hourglass group had the highest rate of pure arterial insufficiency, while veno-occlusive dysfunction was seen most commonly in the ventral curvature group. The ventrolateral group showed the most normal vascular status parameters. CONCLUSIONS: This study demonstrates there is a relationship between the type of curvature and penile hemodynamics. Although patients with PD in the hourglass abnormality group were the youngest, this abnormality was associated with the poorest penile vascular status. Patients with ventrolateral curvature had the best penile hemodynamics in our series. PDDU findings may direct the treating physician to different treatment options.
Diabetes Mellitus↗
Poly(Adenosine diphosphate-ribose) polymerase inhibition preserves erectile function in rats after cavernous nerve injury.
PURPOSE: We investigated the involvement of poly(adenosine diphosphate-ribose) (PAR) polymerase (PARP) activation in the development of erectile dysfunction and the therapeutic benefit of the potent PARP inhibitor INO-1001 (Inotek Pharmaceuticals Corp., Beverly, Massachusetts) in a bilateral cavernous nerve crush injury (BCNCI) model in rats. MATERIALS AND METHODS: Sprague-Dawley rats were divided into 3 groups, namely sham treated, BCNCI plus vehicle and BCNCI plus the PARP inhibitor INO-1001. One week after surgical intervention all groups underwent in vivo cavernous nerve stimulation. PAR activation, nitrotyrosine and inducible nitric oxide synthase were evaluated by immunohistochemistry and serum levels of INO-1001 were measured by high performance liquid chromatography. Penile tissues were analyzed for levels of malondialdehyde and myeloperoxidase. Data sets were statistically compared in all groups. RESULTS: Neurogenic mediated erectile responses were evaluated. Mean intracavernous pressure (ICP), the ICP-to-blood-pressure ratio and total ICP were significantly decreased in BCNCI plus vehicle rats. These values were not statistically different between the sham and PARP inhibitor treated groups. There was a marked decrease in PAR staining in the treatment group. There was a substantial increase in malondialdehyde tissue levels but not myeloperoxidase in response to BCNCI, which was unchanged with PARP inhibitor treatment. There was a marked increase in tyrosine nitration in the treatment group. Up-regulation of nitric oxide synthase and increased tyrosine nitration were not observed in the penile tissues of the treatment group. CONCLUSIONS: These data demonstrate that BCNCI in a rat model causes increased PARP activation, resulting in severe erectile dysfunction. Treatment with the PARP inhibitor INO-1001 decreases the degree of nitrosative stress, prevents PARP activation and provides significant cavernous neuroprotection, which in turn preserves erectile function.
Adenosine Diphosphate Ribose↗
The impact of intralesional interferon alpha-2b injection therapy on penile hemodynamics in men with Peyronie's disease.
INTRODUCTION: Penile duplex Doppler ultrasound (PDDU) is currently the preferred method for the functional evaluation of penile hemodynamics. PDDU may be used to monitor objectively changes in penile vascular parameters in men who undergo treatment for Peyronie's disease (PD), including intralesional interferon alpha-2b (IFN alpha-2b). AIM: To investigate the impact of intralesional IFN alpha-2b therapy for PD on penile hemodynamics by using PDDU and to assess the objective role of PDDU in monitoring treatment outcomes. MATERIALS AND METHODS: Thirty-nine patients (20 in the placebo and 19 in the IFN alpha-2b treatment arm) were enrolled in this prospective, placebo-controlled, parallel study. Patients received either 10 mL saline or 5 x 10(6) units of IFN alpha-2b intralesional injections every other week for a total of six injections. Patients in each group were evaluated at baseline and after completion of treatment regarding changes in penile hemodynamic parameters, penile curvature, plaque size and density, pain on erection, and erectile function. Specific published criteria were used for PDDU measurements. Outcomes were statistically compared between each group by using Mann-Whitney U and chi-square tests. RESULTS: The mean age of the patients and the duration of PD were similar in both groups. The improvement in penile blood flow was significantly greater in IFN alpha-2b-treated patients than those in the placebo group. The number with the nonvascular classification increased significantly in the IFN alpha-2b arm from 31.5% to 57.8%. Additionally, improvements in penile curvature, plaque size and density, and pain on erection were better in the IFN alpha-2b group compared with the control. No significant improvement was observed in the erectile function domain in either group. CONCLUSION: This study reveals that intralesional IFN alpha-2b injections have a significant benefit on penile hemodynamic parameters. Moreover, intralesional IFN alpha-2b is an effective, minimally invasive treatment for PD, and PDDU is a useful adjunct to monitor objectively changes in penile vascular parameters. interferon alpha-2b injection therapy on penile hemodynamics in men with Peyronie's disease.
Adult↗
Superoxide anion production in the rat penis impairs erectile function in diabetes: influence of in vivo extracellular superoxide dismutase gene therapy.
INTRODUCTION: Superoxide anion may contribute to erectile dysfunction (ED) in diabetes mellitus by reducing cavernosal nitric oxide (NO) bioavailability. The purpose of this study was to determine if gene transfer of extracellular superoxide dismutase (EC-SOD) can reduce superoxide anion formation and determine if this reactive oxygen species may contribute to diabetes-related ED in an experimental model of diabetes. METHODS: Three groups of animals were utilized: (1) control; (2) streptozotocin (STZ)-diabetic rats [60 mg/kg intraperitoneally (ip)] intracavernosally injected with AdCMVbetagal (negative control); and (3) STZ-rats intracavernosally injected with AdCMVEC-SOD. Two months after ip injection of STZ, groups 2 and 3 were transfected with the adenoviruses and 2 days after transfection, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Confocal microscopy for superoxide anion and von Willebrand Factor (vWF) was performed in the STZ-diabetic rat. Superoxide anion production, total SOD activity, and cyclic guanosine monophosphate (cGMP) levels were measured in each experimental group of rats. RESULTS: Confocal microscopy demonstrated superoxide in smooth muscle and endothelial cells of the STZ-rat cavernosum and colocalized with vWF in the endothelium. Higher superoxide anion levels and decreased cGMP levels were found in the penis of STZ-rats at a time when erectile function was reduced. Two days after administration of AdCMVEC-SOD, superoxide anion levels were significantly lower in the penis of STZ-rats. Total SOD activity and cavernosal cGMP was increased in the penis of EC-SOD-transfected rats. STZ-rats transfected with AdCMVEC-SOD had a peak intracavernosal pressure (ICP) and total ICP to CNS that was similar to control rats. CONCLUSIONS: These data demonstrate that in vivo adenoviral gene transfer of EC-SOD can reduce corporal superoxide anion levels and raise cavernosal cGMP levels by increasing NO bioavailability thus restoring erectile function in the STZ-diabetic rat.
Adenoviridae↗
The impact of vascular risk factors on erectile function.
The main cause of erectile dysfunction is organic in nature, with vascular etiologies being the most common risk factors. The incidence of erectile dysfunction increases with the number of vascular comorbidities such as hypertension, diabetes, hyperlipidemia, smoking and atherosclerosis. The earliest signal of endothelial damage in men with vascular risk factors is the manifestation of erectile dysfunction. The penis is a barometer of the body's endothelial function, so it is reasonable then to correlate vascular pathologies as direct causes of erectile dysfunction. Moreover, erectile dysfunction may be the first clinical presentation of any of these comorbidities, with the vascular endothelium playing a pivotal role in regulating vascular homeostasis of the corpora cavernosa. This article addresses the impact of vascular risk factors on erectile function based on current evidence.
Arteriosclerosis↗
Endothelial nitric oxide synthase gene therapy for erectile dysfunction.
Basic science research on erectile physiology has been devoted to investigating the pathogenesis of erectile dysfunction (ED) and has led to the conclusion that ED is predominately a disease of vascular origin. It is well recognized that the incidence of ED dramatically increases in men who suffer from diabetes mellitus, hypercholesterolemia, and cardiovascular disease. Endothelial nitric oxide synthase (eNOS) is an important factor in cardiovascular homeostasis, angiogenesis, and erectile function. Given the impact of endothelial-derived nitric oxide (NO) in vascular biology, a great deal of research over the past decade has focused on the role of NO synthesis from the endothelium in normal erectile physiology as well as in disease states. Loss of the functional integrity of the endothelium and subsequent endothelial dysfunction plays an integral role in the occurrence of ED. Therefore, a likely target of gene therapy for the treatment of ED is eNOS. This communication reviews the role of eNOS in erectile physiology and discusses the alterations in eNOS expression in various vascular diseases of the penis. Putative gene therapy interventions to restore eNOS expression and subsequent endothelial function may represent an exciting new therapeutic strategy for the future treatment of ED.
Erectile Dysfunction↗
Penetration and maintenance of erection with vardenafil: a time-from-dosing analysis.
OBJECTIVE: To assess success rates in ability to penetrate (Sexual Encounter Profile question 2 [SEP2]) and maintain erections to completion of intercourse (SEP3) from time of dosing to start of sexual activity in a retrospective analysis of two pivotal trials. METHODS: In two randomized, double-blind studies, men with ED for > 6 months received vardenafil 5 mg, 10 mg, or 20 mg or placebo for 12-26 weeks. Patients were instructed to start sexual activity 1 hour after dosing. In this retrospective pooled analysis, patient diary questions through week 12 were analyzed, providing attempt data was recorded 0-12 hours post-dose. Mean per-patient SEP2 and SEP3 success rates (intent-to-treat population) were calculated by time between dosing and start of sexual activity, from 0-12 hours through week 12. Least-square means and nominal p-values for differences versus placebo were derived by analysis of covariance with terms for baseline, study and treatment. RESULTS: Most attempts at sexual intercourse occurred 30-90 minutes after dosing: 88%-93% of attempts occurred within 120 minutes. SEP2 success rates in patients choosing to attempt sexual activity in each interval from < or = 15 minutes through the 4-8-hour interval were higher with vardenafil compared with placebo, while SEP3 success rates were greater with vardenafil for patients choosing to initiate sexual activity from < or = 15 min through the 8-12-hour interval. The most commonly reported treatment-emergent adverse events in patients receiving vardenafil included headache (11%-22%), flushing (6%-13%), rhinitis (5%-13%), and dyspepsia (2%-7%). CONCLUSION: In this retrospective analysis of two pivotal trials, vardenafil improved success rates compared with placebo in ED patients who attempted intercourse from as early as 15 minutes or less and through 4-8 hours after dosing in ability to penetrate (SEP2) and from as early as 15 minutes or less and through 8-12 hours after dosing in maintenance of erection (SEP3).
Coitus↗
RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: a mechanism for diabetes-associated erectile dysfunction.
Significant impairment in endothelial-derived nitric oxide is present in the diabetic corpus cavernosum. RhoA/Rho-kinase may suppress endothelial nitric oxide synthase (eNOS). Here, we tested the hypothesis that RhoA/Rho-kinase contributes to diabetes-related erectile dysfunction and down-regulation of eNOS in the streptozotocin (STZ)-diabetic rat penis. Colocalization of Rho-kinase and eNOS protein was present in the endothelium of the corpus cavernosum. RhoA/Rho-kinase protein abundance and MYPT-1 phosphorylation at Thr-696 were elevated in the STZ-diabetic rat penis. In addition, eNOS protein expression, cavernosal constitutive NOS activity, and cGMP levels were reduced in the STZ-diabetic penis. To assess the functional role of RhoA/Rho-kinase in the penis, we evaluated the effects of an adeno-associated virus encoding the dominant-negative RhoA mutant (AAVTCMV19NRhoA) on RhoA/Rho-kinase and eNOS and erectile function in vivo in the STZ-diabetic rat. STZ-diabetic rats transfected with AAVCMVT19NRhoA had a reduction in RhoA/Rho-kinase and MYPT-1 phosphorylation at a time when cavernosal eNOS protein, constitutive NOS activity, and cGMP levels were restored to levels found in the control rats. There was a significant decrease in erectile response to cavernosal nerve stimulation in the STZ-diabetic rat. AAVT19NRhoA gene transfer improved erectile responses in the STZ-diabetic rat to values similar to control. These data demonstrate a previously undescribed mechanism for the down-regulation of penile eNOS in diabetes mediated by activation of the RhoA/Rho-kinase pathway. Importantly, these data imply that inhibition of RhoA/Rho-kinase improves eNOS protein content and activity thus restoring erectile function in diabetes.
Adenoviridae↗
Testosterone replacement therapy.
Explore the source record for details and available documents.
Hormone Replacement Therapy↗