他达拉非联合十一酸睾酮治疗伴有睾酮缺乏的中青年男性ED的临床研究

<正>随着社会的发展,勃起功能障碍(erectile dysfunction,ED)的发病率越来越高。1995年全世界约有1.52亿男性患有ED,而到2025年估计患者数将达到3.22亿[1]。20世纪90年代随着5型磷酸二酯酶(PDE5)抑制剂的研制成功,主要的治疗方式逐渐转变为口服PDE5抑制剂。他达拉非作为新一代PDE5抑制剂,可以显著改善勃起功能,帮助患者成功完成性生活,但仍有部分患者按需口服他达拉非治疗ED效果不理想。在存在部分雄激素缺乏     

磷酸二酯酶5抑制剂西地那非和伐地那非治疗勃起功能障碍患者心血管参数改变的研究

西地那非是勃起功能障碍(ED)患者最常用的口服处方药。伐地那非是由美国FDA去年批准应用治疗各种原因引起的ED的一种新型的磷酸二酯酶5(PDE5)型抑制剂。这两种PDE5抑制剂通过一氧化氮环磷酸鸟苷途径舒张血管,影响血压(BP)。为了观察这两种PDE5抑制剂对血压正常的ED患者血压和心率(HR)     

PDE5抑制剂对IVF中临时性ED患者的治疗效果及其对精液的影响

目的 探讨5型磷酸二酯酶(PDE5)抑制剂对常规体外受精(IVF)中临时性勃起功能障碍(ED)患者的治疗效果及其对精液的影响.方法 根据服用不同的PDE5抑制剂将89名临时性ED患者分为三组:他达拉非组、伐地那非组和西地那非组,观察患者获取精液的成功率,比较三组患者服药前1个月和服药后3h内的精液量、精液密度和精子活动力(a级+b级).结果 76(85.4%)名患者勃起功能改善,成功获取精液,三组患者的取精成功率差异无统计学意义(P>0.05);与服药前相比,三组患者服药后的精液量、精子密度及精子活动力差异无统计学意义(P>0.05).结论 PDE5抑制剂是治疗临时性ED患者的有效药物,PDE5抑制剂对IVF中临时性ED患者的精液参数无明显影响.     

他达拉非治疗合并心血管疾病的ED患者及对心血管的保护作用

磷酸二酯酶5(PDE5)广泛分布于心脏、血管、平滑肌等组织器官,可催化环磷酸鸟苷(cGMP)水解产生血管扩张效应,同时也是一氧化氮(NO)的供体物质。他达拉非是首个获的FDA批准用于治疗勃起功能障碍(ED)的PDE 5抑制剂类药物,可选择性抑制PDE5。多个临床研究显示,对于合并心血管疾病(冠心病、高血压、慢性心脏衰竭、肺动脉高压)、糖尿病等疾病的ED患者,他达拉非不仅可以改善ED症状,同时可通过改善血管内皮细胞功能、增加内皮细胞源性NO水平、激活心肌细胞蛋白激酶A,上调细胞内钙离子浓度及改善血流动力学指标等作用,发挥其对ED患者的心血管保护作用,改善ED患者的生存质量。因此,他达拉非等PDE 5抑制剂类药物可作为合并心血管疾病的ED患者治疗用药选择之一。     

PDE5抑制剂治疗LUTS的进展及意义

勃起功能障碍及下尿路症状均为中老年男性常见疾病,多个流行病学研究证实二者密切相关。近年来多项研究证实PDE5抑制剂在改善ED患者勃起功能的同时,可有效改善患者的LUTS,但对患者的尿动力学指标无改善。本文就国内外ED与LUTS之间的联系、PDE5抑制剂治疗LUTs的进展及其可能的机制做一概述。     

他达拉非每日一次方案治疗男性勃起功能障碍的研究概述

正勃起功能障碍(erectile dysfunction,ED)常见于年龄超过40岁的中老年男性,即持续不能达到或维持足够勃起以完成满意性交,严重影响患者及配偶的生活质量~([1])。对于ED的治疗经历了很多阶段,20世纪90年代随着5型磷酸二酯酶(phosphodiesterase type5,PDE5)抑制剂的面世,主要的治疗方式逐渐转变为口服PDE5抑制剂。西地那非是1998年3月美国食品药品监督管理局(Food and Drug Administration,     

良性前列腺增生/下尿路症状合并勃起功能障碍治疗的新靶点——PDE5

伴有下尿路症状(LUTS)的良性前列腺增生(BPH)是中老年男性常见病和多发病,其发病率随着年龄的增长而显著升高。研究表明,BPH/LUTS和勃起功能障碍(ED)之间密切相关,并对中老年男性的生活质量产生重要影响。磷酸二酯酶5抑制剂(PDE5i)在治疗ED的同时,可改善患者的BPH/LUTS,PDE5有望作为BPH/LUTS合并ED治疗的新靶点。对PDE5的结构、功能以及PDE5i的作用机制进一步探索,可为BPH/LUTS合并ED的临床治疗提供更加有效的策略。     

伐地那非治疗耻骨后前列腺根治切除术后的勃起功能障碍

超过三分之一的患者在行保留性神经的前列腺根治切除术后会出现勃起功能障碍(ED)。最近的研究表明,磷酸二酯酶 5(PDE5)抑制剂伐地那非可改善保留单侧或双侧神经的耻骨后前列腺根治切除术后ED患者的勃起功能,而且安全性良好。     

他达拉非:ED患者及其配偶的选择偏爱?

勃起功能障碍(erectile dysfunction,ED)是男性常见疾病,直接影响患者及其配偶的生活质量。PDE5抑制剂是治疗ED的首选药物。尽管临床主要有3种PDE5抑制剂(西地那非、伐地那非和他达拉非)可供选择,但是患者及其配偶在选择PDE5抑制剂上是否有偏好,以及影响其选择的因素又有哪些本文简要地综述了最近的研究进展。     

难治性勃起功能障碍的研究进展

勃起功能障碍(ED)是一种常见病、多发病。目前主要是首选PDE5抑制剂(PDE5I)治疗,总有效率可达80%,部分患者尤其是伴有糖尿病﹑心血管疾病及前列腺癌根治术后者,单独应用PDE5I效果不佳,称为难治性ED。除了NO-cGMP通路外,勃起与ED的发生过程还涉及多条信号通路(RhoA/Rho激酶、H2S、CO等),复杂的信号网络构成了难治性ED发生的基础,以PDE5I为主的交替治疗、联合治疗等可提高对难治性ED治疗成功率。本文就对PDE5I治疗无效的难治性ED的研究进展作一综述。     

Pharmacological management of erectile dysfunction

Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men worldwide. Many drugs are now available for treating ED; oral pharmacotherapy represents the first-line option for most patients with ED. Sildenafil, an inhibitor of the enzyme phosphodiesterase type 5, is currently the most widely prescribed oral agent and has a very satisfactory efficacy-safety profile in all patient categories. Apomorphine SL is a dopamine D1- and D2-receptor agonist which has recently been approved for marketing in Europe. It is best selected for treating patients with mild to moderate ED. Vardenafil and tadalafil are new phosphodiesterase type 5 inhibitors which are expected to be approved this year. Both of them have significant positive efficacy-safety profiles. Patients who do not respond to oral pharmacotherapy or who cannot use it are good candidates for intracavernosal and intraurethral therapy. Alprostadil is the most widely used drug, both for injection therapy and for the intraurethral route. The efficacy of second-line treatment is high but the attrition rate remains significant.     

Testosterone and Erection: Practical Management for the Patient with Erectile Dysfunction

Although erectile dysfunction (ED) and testosterone deficiency syndrome are two independently distributed disorders, there is a degree of overlap between them. Testosterone replacement therapy, either alone or combined with other treatments such as a phosphodiesterase type 5 (PDE5) inhibitor, may therefore be useful in some men with ED. Corrective treatment of ED includes sex therapy, risk factor modification, chronic usage of PDE5 inhibitors, and testosterone replacement. Studies have shown that testosterone replacement in men with hypogonadism improves libido and erectile function in a significant proportion of cases. If corrective treatment fails or is not indicated, symptomatic treatments such as oral PDE5 inhibitors or intraurethral/intracavernous therapy are available. PDE5 inhibitors are an excellent first-line choice, although a significant proportion of men still fail to respond to monotherapy. Testosterone deficiency may be overlooked in some men with ED and, because this may be associated with lower expression of PDE5 in the penis, it could result in failure of PDE5 inhibitor therapy. Recent recommendations, therefore, suggest the need for combination therapy in some patients. In conclusion, all men presenting with ED should have their testosterone levels checked, and testosterone replacement should be considered in those with low levels. Testosterone replacement should also be considered in hypogonadal men with ED not responding to PDE5 inhibitors. If erections remain insufficient after 3 mo, a combination of testosterone and a PDE5 inhibitor may be beneficial.     

Centrally acting mechanisms for the treatment of male sexual dysfunction

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.     

Gene therapy and erectile dysfunction： the current status

Current available treatment options for erectile dysfunction （ED） are effective but not without failure and/or side effects. Although the development of phosphodiesterase type 5 （PDE5） inhibitors （i.e. sildenafil, tadalafil and vardenafil） has revolutionized the treatment of ED, these oral medications require on-demand access and are not as effective in treating ED related to diabetic, post-prostatectomy and severe veno-occlusive disease states. Improvement in the treatment of ED is dependent on understanding the regulation of human corporal smooth muscle tone and on the identification of relevant molecular targets. Future ED therapies might consider the application of molecular technologies such as gene therapy. As a potential therapeutic tool, gene therapy might provide an effective and specific means for altering intracavernous pressure ＂on demand＂ without affecting resting penile function. However, the safety of gene therapy remains a major hurdle to overcome before being accepted as a mainstream treatment for ED. Gene therapy aims to cure the underlying conditions in ED, including fibrosis. Furthermore, gene therapy might help prolong the efficacy of the PDE5 inhibitors by improving penile nitric oxide bioactivity. It is feasible to apply gene therapy to the penis because of its location and accessibility, low penile circulatory flow in the flaccid state and the presence of endothelial lined （lacunar） spaces. This review provides a brief insight of the current role of gene therapy in the management of ED.     

Erectile dysfunction and cardiac disease: Recommendations of the second princeton conference

Erectile dysfunction (ED) has been linked increasingly to cardiovascular risk factors and comorbidities. Considering the potential risk associated with sexual activity, guidelines were developed (Princeton I) for assessment and management of patients with varying degrees of cardiac risk. These guidelines were recently updated (Princeton II) based on new data concerning the link between ED and cardiovascular disease and the availability of additional phosphodiesterase type 5 inhibitors (vardenafil, tadalafil). Despite the need for careful risk assessment in all cases, sexual activity remains safe for the large majority of patients. However, all patients presenting with complaints of ED should be carefully assessed for the presence of cardiovascular risk factors (eg, obesity, hypertension, hyperlipidemia). Risk-factor modification, including lifestyle interventions (eg, exercise, weight loss) is strongly encouraged. Guidelines are presented for the management of acute coronary syndromes in patients taking phosphodiesterase type 5 inhibitors, including alternatives to the use of nitrates for these patients. Other drug interactions and the cardiovascular safety of testosterone replacement therapy are considered.     

他达拉非独特的时间顾虑收益

社会心理因素在勃起功能障碍(ED)的发病过程中占到了十分重要的地位。一种理想的治疗药物应能给患者及其伴侣带来满意的社会心理收益。"心理与人际关系量表"(PAIRS量表)既能评价ED对患者及其伴侣的心理及人际关系影响,又能预测ED患者对治疗的满意度。利用PAIRS量表对5型磷酸二酯酶(phosphodies-terasetype5,PDE5)抑制剂治疗ED的疗效进行评估,发现在降低ED患者性活动相关性时间顾虑方面,他达拉非明显优于西地那非和伐地那非。这也正是ED患者及其伴侣在临床治疗条件下偏好使用他达拉非的深层原因。与此相关的药物属性则是他达拉非长达36h的卓越疗效。     

Gene Therapy for Erectile Dysfunction: Fact or Fiction?

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.     

他达拉非治疗ED疗效和安全性新进展

他达拉非——长效5型磷酸二酯酶(PDE5)抑制剂是治疗勃起功能障碍(ED)的首选药物之一。许多临床研究证实其在普通ED患者、老年患者以及伴有糖尿病、脊髓损伤或前列腺癌术后患者中有较好的疗效和良好的安全性及耐受性,而且其独特的长达36 h的时间窗不仅增强了患者的自信心,更改善了患者及其伴侣的生活质量。     

伐地那非治疗糖尿病患者的勃起功能障碍

勃起功能障碍 (erectiledysfunction ,ED)在糖尿病患者中发生率要高于非糖尿病人群 ,而且更难治疗。伐地那非是一种高选择性的新型磷酸二酯酶 5抑制剂 ,是广泛ED人群的一线治疗药物。最近发表的大型临床试验表明 ,无论糖尿病合并ED的患者基线时的病情严重程度如何 ,也无论他们的血糖控制情况如何 ,伐地那非都能有效地改善其勃起功能 ,而且使用安全 ,耐受性良好