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1.
The present paper serves as a review of the associations between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED), with a focus on common and combined pathways for treatment. LUTS and ED are common conditions seen in general urologic practice. Research has started to establish epidemiologic and pathophysiologic links between the two conditions and a strong association confirmed across multiple studies. Men seeking care for one condition should always be interviewed for complaints of the other condition. Proposed common pathways include α-1 adrenergic receptor imbalance, Rho-kinase overactivity, endothelial cell dysfunction and atherosclerosis-induced ischemia. Medical therapy has replaced surgery as the first-line treatment for LUTS in most patients, with the incorporation of α-adrenergic receptor antagonists (α-ARAs) and 5-α-reductase inhibitors (5-ARIs) into everyday practice. Treatment with α-ARAs contributes to some improvement in ED, whereas use of 5-ARIs results in worsened sexual function in some patients. Phosphodiesterase-5 (PDE-5) inhibitors have revolutionized the treatment of ED with a simple oral regimen, and new insights demonstrate a benefit of combined use of PDE-5 inhibitors and α-ARAs. The mechanisms of action of these medications support these observed benefits, and they are being studied in the basic science and clinical settings. In addition, novel mechanisms for therapy have been proposed based on clinical and research observations. The minimally invasive and surgical treatments for LUTS are known to have adverse effects on ejaculatory function, while their effects on erectile function are still debated. Much remains to be investigated, but it is clear that the associations between LUTS and ED lay the foundation for future therapies and possible preventative strategies.  相似文献   

2.
Priapism is defined as abnormal prolonged penile erection occurring beyond or unrelated to sexual interest. The disorder is enigmatic yet devastating because of its elusive etiology, irreversible erectile tissue damage, and resultant erectile dysfunction (ED). Current management strategies suffer from a poor understanding of the pathophysiology, especially at the molecular level. The traditional treatments are based more on empirical rather than evidence-based knowledge. The outcomes for restoration of normal erectile function are poor, especially for stuttering priapism. Therefore, it is critical to understand priapism from a molecular level, to formulate treatment strategies and to establish rational prevention strategies for high-risk populations, such as sickle cell disease (SCD) patients and cases of the stuttering variant. This review focuses on the recent advances at the molecular level in priapism and penile erection, and applies the recent knowledge to the treatment of stuttering priapism.  相似文献   

3.
Erectile dysfunction (ED) commonly results from endothelial dysfunction of the systemic vasculature. Although phosphodiesterase type 5 (PDE-5) inhibitors are effective at treating most cases of ED, they must be taken routinely and are ineffectual for a meaningful number of men. In recent years gene and stem cell-based therapies targeted at the penile endothelium have been gaining momentum in preclinical studies. These early studies reveal that gene and stem cell-based therapies may be both enduring and efficacious, and may eventually lead to a cure for ED. The following review will highlight our current understanding of endothelial-specific gene and stem cell-based therapies performed to date in a number of experimental animal models.  相似文献   

4.
Urinary incontinence (UI) and erectile dysfunction (ED) are both very prevalent conditions. Insertion of an artificial urinary sphincter (AUS) and penile prosthesis (PP) is an effective and proven method of treatment for both conditions. With advancing age, as well as with increasing populations of patients radically treated for prostate cancer, the occurrence of both conditions found in the same patient is increasing. The purpose of this article was to analyze the available evidence for simultaneous surgical management of male ED and UI using prosthetic devices. The existing literature pertaining to dual implantation of AUS and PP was reviewed. The concomitant insertion of the PP with the male perineal sling was also considered. Concurrent ED and UI are increasingly seen in the post radical prostatectomy population, who are often younger and less willing to suffer with these conditions. Insertion of an AUS and PP, either simultaneously or as a two-stage procedure, appears to be a safe, efficacious and long-lasting method of treatment. The improvements in design of both the AUS and PP as well as the development of the single transverse scrotal incision have made simultaneous insertion of these prostheses possible. Dual implantation of the PP and male sling looks promising in a selected population. In conclusion, the insertion of the AUS and PP for the treatment of concurrent UI and ED is safe and effective. Simultaneous insertion of these prostheses in the same patient offers potential advantages in operative and recovery time and is associated with high patient satisfaction. Combination therapy should therefore be included in the arsenal of treatment of these conditions.  相似文献   

5.
Erectile response is centrally and peripherally regulated by androgens.The original insights into the mechanismsof action of androgens were that androgens particularly exert effects on libido and that erections in response to eroticstimuli were relatively androgen-independent.It was shown that sexual functions in men required androgen levels atthe low end of reference values of testosterone.So it seemed that testosterone was not useful treatment for men witherectile difficulties,particularly following the advent of the phosphodiesterase type 5(PDE5)inhibitors.However,approximately 50% of those treated with PDE5 inhibitors discontinue their treatment.A number of recent develop-ments shed new light on testosterone treatment of erectile dysfunction(ED)in aging men.(1)A recent insight is that,in contrast to younger men,elderly men might require higher levels of testosterone for normal sexual functioning.(2)Several studies have indicated that PDE5 inhibitors are not always sufficient to restore erectile potency in men,andthat testosterone improves the therapeutical response to PDE5 inhibitors considerably.(3)There is growing insightthat testosterone has profound effects on tissues of the penis involved in the mechanism of erection and that testoster-one deficiency impairs the anatomical and physiological substrate of erectile capacity,reversible upon androgenreplacement.The synthesis of PDE5 is upregulated by androgens,and the arterial inflow into the penis is improved bygiving androgen.The above invites a re-examination of the merits of giving testosterone to aging men with ED.Thebeneficial effects of PDE5 inhibitors may only be optimally expressed in a eugonadal environment.(Asian J Androl2006 Jan;8:3-9)  相似文献   

6.
The past decade has seen an explosion of new information on the physiology of penile erection, and pathophysiology of erectile dysfunction (ED). Hypercholesterolemia is a chronic condition that can lead to degeneration in the vasculature bed and can result in ED if the penile vasculature is involved. Angiogenesis is the growth of new blood vessels from preexisting vasculature. Therapeutic angiogenesis seeks to harness the mechanisms of vascular growth to treat disorders of inadequate tissue perfusion, such as coronary artery disease and ED. There have been tremendous changes in the field of therapeutic angiogenesis over the past decade, and there is much promise for the future. Initial preclinical work with cytokine growth factor delivery resulted in a great deal of enthusiasm for the treatment of ischemic heart and/or peripheral vascular disease, though clinical studies have not achieved similar success. With an increased understanding of the complex mechanisms involved in angiogenesis, novel therapies which target multiple different angiogenic pathways are also being developed and tested. The penis is a convenient tissue target for gene therapy because of its external location and accessibility, the ubiquity of endothelial lined spaces, and low level of blood flow, especially in the flaccid state. Therapeutic angiogenesis is an exciting field that continues to evolve. This review will focus on the development of growth factors for hypercholesterolemic ED, the use of various growth factors for ED therapy, their routes of delivery, and the results in animal studies.  相似文献   

7.
Predicting treatment responses in advanced prostate cancer (PCa) currently centres on prostate-specific antigen (PSA) kinetics and on being able to visualize measurable changes in imaging modalities. New molecular markers have emerged as potential diagnostic and prognostic indicators; these were summarized in Part I of this review in the Asian Journal ofAndrology. A number of molecular markers are now being used to enhance PCa imaging and staging. However, management options for advanced and hormone-resistant PCa (HRPC) are limited and additional therapeutic options are needed. Molecular markers have been proposed as potential therapeutic targets using gene therapy and immunomodulation. Additionally, markers identified in early PCa and precursor lesions may offer novel targets for chemoprevention and vaccine development. This review summarizes the current advances regarding the roles of these markers in the management of PCa.  相似文献   

8.
Aim: To discuss important points on medical history, preoperative evaluation, real expectations, and selection of the appropriate surgical procedure to improve patient satisfaction after surgical procedures for Peyronie's disease. Methods: Recent advances in approaches to Peyronie's disease are discussed based on the literature and personal experiences. Issues concerning surgical indication, patient selection, surgical techniques, and grafting are discussed. Lengthening procedures on the convex side of the penile curvature by means of grafting offer the best possible gain from a reconstruction standpoint. Penile rectification and rigidity are required to achieve a completely functional penis. Most patients experience associated erectile dysfunction (ED), and penile straightening alone may not be enough to restore complete function. Twenty-five patients were submitted to total penile reconstruction on length and girth with concomitant penile prosthesis implant. The maximum length restoration was possible and limited by the length of the dissected neurovascular bundle. The mean age was 55.4 years (32-69 years) and the mean angle of curvature 74.2± 22.4° (0-100°). Pericardial grafting was used to cover the defect. The mean follow-up time was 11.2 ± 5.9 months (3-22 months). Results: Mean functional penile length gain was 3.40 + 0.73 cm (2-5 cm). Penile prosthesis maintained the penis straight. No infections occurred. Sexual intercourse was restored in all patients and all reported recovered self-esteem. Conclusion: Improving patient satisfaction with the surgical treatment includes proper preoperative evaluation on stable disease, penile shortening, vascular and erectile status, patient decision and selection as well as extensive discussion on surgical technique for restoring functional penis (length and rigidity). Length and girth restoration is very important for self-esteem and patient satisfaction.  相似文献   

9.
The behavior of Chinese patients seeking help for erectile dysfunction (ED) has not been described in detail. This was an observational study conducted using an outpatient clinic-based questionnaire survey of ED patients. From 2008 to 2009, physicians in 10 medical centers in China enrolled 2693 men (aged 25-70years) diagnosed with ED. The diagnosis was based on the International Index of Erectile Function 5 (IIEF-5) Questionnaire. The men completed a survey that asked questions about demographics, marital status, education level and household income as well as help-seeking behavior and awareness of medical therapy. The mean age of the 2693 men was 43.4 5.3years; 73% were 〈50-years-old and 49% had a high household income. The mean time between noticing ED and taking the first treatment was 4.3 2.1months. Of the 2577 respondents, physicians (54%) and the internet (52%) were most frequently consulted sources for information about ED. Young ED patients preferred using the internet and older patients preferred consulting with physicians. Western medicine (19%) and traditional Chinese medicine (16%) were most frequently used for treatment. Young ED patients preferred to first search the internet for information, whereas older patients first asked physicians for help. Side effects of treatment were the greatest concern, especially for older patients. Physicians and the internet are frequently consulted for ED information and therapy. On the basis of these survey results, we believe that physicians in China should enhance health education about ED, especially via the internet.  相似文献   

10.
To evaluate the effect of statins for erectile dysfunction (ED), a systematic review of the literature was conducted in the Cochrane Library, Embase and PubMed from the inception of each database to June 2013. Only randomized controlled trials (RCTs) comparing treatment for ED with statins were identified. Placebo RCTs with the International Index of Erectile Function (IIEF) as the outcome measure were eligible for meta-analysis. A total of seven RCTs including two statins with a total of 586 patients strictly met our criteria for systematic review and five of them qualified for the meta-analysis. A meta-analysis using a random effects model showed that statins were associated with a significant increase in IIEF-5 scores (mean difference (MD): 3.27; 95% confidential interval (CI):1.51 to 5.02; P〈 0.01) and an overall improvement of lipid profiles including total cholesterol (MD: -1.08; 95% Ch -1.68 to -0.48; P 〈 0.01), low-density lipoprotein (LDL) cholesterol (MD: -1.43; 95% Ch -2.07 to -0.79; P 〈 0.01), high-density lipoprotein (HDL) cholesterol (MD: 0.24; 95% Ch 0.13 to 0.35; P〈 0.01) and triglycerides (TGs) (MD. -0.55; 95% Ch -0.61 to -0.48; P 〈 0.01). In summary, our study revealed positive consequences of these lipid-lowering drugs on erectile function, especially for nonresponders to phosphodiesterase type 5 inhibitors (PDE51s). However, it has been reported that statin therapy may reduce levels of testosterone and aggravate symptoms of ED. Therefore, larger, well-designed RCTs are needed to investigate the double-edged role of statins in the treatment of ED.  相似文献   

11.
Erectile dysfunction (ED) is defined as the inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance. ED is a highly prevalent health problem with considerable impact on the quality of life of men and their partners. Although the treatment of ED with oral phosphodiesterase type V (PDE5) inhibitors is effective in a wide range of individuals, it is not efficacious in all patients. The failure of PDE5 inhibitors happens mainly in men with diabetes, non-nerve sparing radical prostatectomy, and high disease severity. Therefore, improved therapies based on a better understanding of the fundamental issues in erectile physiology and pathophysiology have recently been proposed. Here, we summarize studies on ED treatment using gene and stem cell therapies. Adenoviral-mediated intracavernosal transfer of therapeutic genes, such as endothelial nitric oxide synthase (eNOS), calcitonin gene-related peptide (CGRP), superoxide dismutase (SOD), and RhoA/Rho kinase and mesenchymal stem cell-based cell and gene therapy strategy for the treatment of age- and diabetes-related ED are the focus of this review.  相似文献   

12.
OBJECTIVES: Erectile dysfunction (ED) is a major health problem that seriously affects the quality of life of patients and their partners. Although all three selective phosphodiesterase type 5 inhibitors (PDE5-Is) are effective in the majority of ED cases, PDE5-I therapy is less efficacious in some hard-to-treat populations (diabetics, men after radical prostatectomy), prompting the development of new approaches, including gene therapy strategies for ED. METHODS: Gene therapy approaches are discussed in terms of the possible role of gene therapy for the treatment of ED, potential targets for gene transfer, vectors to carry targeted genes, and gene strategies for ED in certain disease states, such as diabetes, ageing, arterial and venogenic insufficiency, and cavernous nerve injury. RESULTS: The penis is a convenient tissue target for gene therapy because of its external location and accessibility, the ubiquity of endothelial-lined spaces, and low level of blood flow, especially in the flaccid state. Gene therapy approaches have focused on a number of signaling pathways that are crucial for penile erection, such as nitric oxide/cyclic guanosine monophosphate, RhoA/Rho-kinase, growth factors, ion channels, peptides, and control of oxidative stress. CONCLUSIONS: The need for effective ED therapies in difficult-to-treat patients has encouraged investigators to seek novel modalities for the treatment of ED. Recent preclinical and clinical trials have demonstrated that gene therapy strategies may be feasible for these purposes.  相似文献   

13.
PDE5抑制剂治疗缺血再灌注损伤研究进展   总被引:1,自引:1,他引:0  
Hu YY  Wu ZG 《中华男科学杂志》2011,17(9):842-846
5型磷酸二酯酶(PDE5)抑制剂常用于治疗男性阴茎勃起功能障碍。近年来,有实验研究表明PDE5抑制剂可用于治疗器官组织缺血再灌注损伤,本文就PDE5抑制剂治疗缺血再灌注损伤的基础和临床研究成果作一综述,以期为临床医生选择使用PDE5抑制剂提供理论依据。  相似文献   

14.
The molecular science of erection physiology has established that phosphodiesterase 5 (PDE5) serves an important biological role in the penis. Current research in the field has revealed this molecular effector to be relevant for penile erection, controlling the erectile response by degrading the second messenger product of the erection mediatory nitric oxide (NO) signaling pathway, 3', 5'-cyclic guanosine monophosphate. Accordingly, PDE5 has been targeted for sexual medicine purposes, and orally administered PDE5 inhibitors such as sildenafil, tadalafil, and vardenafil comprise a foremost intervention for erectile dysfunction (ED). New investigation of PDE5 regulation in the penis has suggested alternative roles for the enzyme and new therapeutic opportunities involving its molecular interactions. In particular, PDE5 function is altered under derangements of androgen deficiency, decreased NO bioactivity, and oxidative stress-associated inflammatory changes, thus contributing to an assortment of erectile disorders including hypogonadism-associated ED, recurrent ischemic priapism, penile vasculopathy, and penile fibrosis. This review provides a critical examination of the multifaceted role of the PDE5 regulatory system in the penis and its relevance for applying existing and emerging therapeutic strategies for erectile disorders.  相似文献   

15.
Centrally acting mechanisms for the treatment of male sexual dysfunction   总被引:1,自引:0,他引:1  
The development of pharmacologic therapy for erectile dysfunction (ED) has been possible because of incremental growth in our understanding of the physiology of normal erections and the complex pathophysiology of ED. Although the oral phosphodiesterase type 5 (PDE5) inhibitors have provided safe, effective treatment of ED for some men, a large proportion of men who have ED do not respond to PDE5 inhibitors or become less responsive or less satisfied as the duration of therapy increases. Also, men who are receiving organic nitrates and nitrates, such as amyl nitrate, cannot take PDE5 inhibitors because of nitrate interactions. The current options for treatment beyond PDE5 inhibitors are invasive, unappealing to some patients, and sometimes ineffective. The search for other options by which ED can be treated has branched out and now encompasses centrally acting mechanisms that control erectile function. Drugs available in Europe include apomorphine. This article focuses on the mechanism of centrally acting agents and reviews clinical data on potential new centrally acting drugs for men who have ED.  相似文献   

16.
Sexual dysfunction is very common after treatment of prostate cancer. Radiation therapy together with radical prostatectomy is the most effective treatment for localized disease. Percentages of erectile dysfunction (ED) reported in prospective studies after external-beam radiotherapy (RT) vary from 60-70%, and these are similar after brachytherapy. In randomized trials more realistic percentages of 30-40% are reported. Modern techniques do not seem to decrease post-radiation ED. No final conclusions can be drawn whether or not the radiation dose to the penile structures correlates with post-radiation ED in patients treated for prostate cancer. The etiology of ED after RT of prostate cancer is most probably multi-factorial. The phosphodiesterase type 5 inhibitors (PDE5-I) sildenafil and tadalafil have been shown to be effective to treat post-radiation ED in about half of the patients in randomized trials. Patients and their partners need to be adequately counselled on the effects of cancer treatment on their sexual life and relationship, and about the different treatment possibilities. Sexual counselling has not become yet a routine part of oncology care in most hospitals, but this should be provided. Due to the lack of robust data, prevention of post-radiation ED with PDE5-I cannot be recommended so far.  相似文献   

17.

Background

Low-intensity extracorporeal shockwave therapy (LI-ESWT) is currently under investigation regarding its ability to promote neovascularization in different organs.

Objective

To evaluate the effect of LI-ESWT on men with erectile dysfunction (ED) who have previously responded to oral phosphodiesterase type 5 inhibitors (PDE5-I).

Design, setting, and participants

We screened 20 men with vasculogenic ED who had International Index of Erectile Function ED (IIEF-ED) domain scores between 5–19 (average: 13.5) and abnormal nocturnal penile tumescence (NPT) parameters. Shockwave therapy comprised two treatment sessions per week for 3 wk, which were repeated after a 3-wk no-treatment interval.

Intervention

LI-ESWT was applied to the penile shaft and crura at five different sites.

Measurements

Assessment of erectile function was performed at screening and at 1 mo after the end of the two treatment sessions using validated sexual function questionnaires, NPT parameters, and penile and systemic endothelial function testing. The IIEF-ED questionnaire was answered at the 3- and 6-mo follow-up examinations.

Results and limitations

We treated 20 middle-aged men (average age: 56.1 yr) with vasculogenic ED (mean duration: 34.7 mo). Eighteen had cardiovascular risk factors. At 1 mo follow-up, significant increases in IIEF-ED domain scores were recorded in all men (20.9 ± 5.8 vs 13.5 ± 4.1, p < 0.001); these remained unchanged at 6 mo. Moreover, significant increases in the duration of erection and penile rigidity, and significant improvement in penile endothelial function were demonstrated. Ten men did not require any PDE5-I therapy after 6-mo follow-up. No pain was reported from the treatment and no adverse events were noted during follow-up.

Conclusions

This is the first study that assessed the efficacy of LI-ESWT for ED. This approach was tolerable and effective, suggesting a physiologic impact on cavernosal hemodynamics. Its main advantages are the potential to improve erectile function and to contribute to penile rehabilitation without pharmacotherapy. The short-term results are promising, yet demand further evaluation with larger sham-control cohorts and longer follow-up.  相似文献   

18.
The role of low testosterone levels in erectile dysfunction (ED) remains unclear. Both organic and psychogenic factors contribute to ED, with vasculogenic causes being the most common etiology. Approximately 10-20% of patients with ED are diagnosed with hormonal abnormalities. At the physiologic level, two second messenger systems are involved in mediating erections, one involving cyclic adenosine monophosphate (cAMP) and the other involving cyclic guanosine monophosphate (cGMP). PDE5 inhibitors such as sildenafil promote the cGMP pathway, while alprostadil affects the cAMP pathway. Evidence is strong that, in animal systems, testosterone has direct effects on erectile tissue. However, although testosterone clearly has an impact on libido in humans, its effect on penile function is less clear. Evaluation of ED includes medical, sexual, and psychosocial history assessments, as well as laboratory tests to check for diabetes and hormonal abnormalities. Initial interventions should involve correction of potentially reversible causes of ED, such as hypogonadism. First-line therapy for other patients is typically oral PDE5 inhibitors, such as sildenafil, tadalafil, or vardenafil. For patients who fail treatment with PDE5 inhibitors, local therapies such as intracavernous alprostadil are highly successful. Recent data also support the success of combination therapy with sildenafil and testosterone. This opens the possibility of other combinations of testosterone and other treatments of ED. The ability to exploit multiple pathways in the physiologic processes leading to erection may help improve therapy for ED.  相似文献   

19.
Phosphodiesterase 5 (PDE5) inhibitors prevent the normal hydrolysis of cGMP. As the resulting cGMP accumulation facilitates penile smooth muscle relaxation, PDE5 inhibitors can partially reverse deficiencies in the nitric oxide (NO)/cGMP pathway to treat erectile dysfunction (ED). However, approximately 30-40% of men with ED do not respond to drug therapy. Patients with severe neurologic damage, diabetes mellitus, or severe vascular disease may be resistant to PDE5 inhibitors. Decreased expression or activity of neuronal or endothelial NO synthase (NOS), impaired NO release, or NO destruction will preclude sufficient cGMP formation to permit PDE5 inhibitor efficacy. This article discusses the possible reasons for unresponsiveness and strategies to overcome it. Therapeutic approaches proposed to increase available NO in penile tissue include facilitating NO release by using alpha-2 antagonists, enhancing NO synthesis by providing more substrate for the reaction, and using antioxidants to inhibit NO breakdown by reactive oxygen species.  相似文献   

20.

Context

Erectile dysfunction (ED) after radical prostatectomy (RP) has a significant negative impact on a patient's health-related quality of life. Phosphodiesterase type 5 inhibitors (PDE5-Is) have recently been utilized not only as a treatment of ED in this population but also as a preventive strategy in penile rehabilitation programs.

Objective

To elucidate the pathophysiologic mechanisms of post-RP ED, to assess the need for rehabilitation following surgery, and to analyze the basic scientific evidence and clinical applications of PDE5-Is for the prevention and treatment of ED.

Evidence acquisition

A systematic review of the literature using Medline, Cancerlit, and the Cochrane Library was conducted for the period between January 1997 and June 2008 using the keywords erectile dysfunction, radical prostatectomy, and phosphodiesterase inhibitors. Efficacy and safety of PDE5-Is in the randomized, placebo-controlled trials are evaluated in this review, and the limitations of the remaining studies are also discussed.

Evidence synthesis

Post-RP ED has many factors. Cavernosal nerve injury induces pro-apoptotic factors (ie, loss of smooth muscle) and pro-fibrotic factors (ie, an increase in collagen) within the corpora cavernosa. Cavernosal changes may also be attributed to poor oxygenation due to hemodynamic changes. Experimental data support the concept of cavernosal damage and suggest a protective role for daily dosage of a PDE5-I; however, similar data have not yet been replicated in humans. Penile rehabilitation programs are common in clinical practice, but there is no definitive evidence to support their use or the best treatment strategy. PDE5-Is are efficacious and safe in young patients with normal preoperative erectile function who have undergone bilateral nerve-sparing radical prostatectomy. On-demand use of a PDE5-I may be at least as efficacious as daily use. PDE5-I use in penile rehabilitation programs is not supported by rigorous level 1 evidence-based medicine.

Conclusions

PDE5-Is are an efficacious and safe treatment for post-RP ED in properly selected patients. The experimental results on the protective role of daily dosages of PDE5-Is, while robust, have not been replicated in humans. With current human data, the role of a PDE5-I alone as a rehabilitation strategy is unclear and deserves further investigation.  相似文献   

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