全面康复:勃起功能障碍治疗的新目标

5型磷酸二酯酶(PDE5)抑制剂有效改善勃起功能障碍(ED)患者的勃起功能。枸橼酸西地那非的应用范围不断扩展,肺动脉高压已成为新的适应证。临床研究发现,西地那非能改善多种血管性疾病患者的内皮功能。在ED领域的研究进展包括:动物实验发现,西地那非可以改善海绵体内皮功能,增强磷酸化内皮型一氧化氮合酶(eNOS)蛋白表达,逆转缺血或缺氧导致的海绵体内压(ICP)降低。临床研究证实,西地那非可以使50%以上ED患者阴茎勃起恢复到最充分的硬度(4级勃起);使50%以上保留神经的根治性前列腺切除术后患者勃起功能康复,自发产生足以性交的勃起;使ED患者的自尊心、自信心和性关系满意度等社会心理功能恢复正常。从勃起功能到社会心理功能的全面恢复可能成为今后ED治疗的新目标。     

The effects of chronic phosphodiesterase-5 inhibitor use on different organ systems

Phosphodiesterase-5 (PDE-5) inhibitors selectively inhibit PDE-5 enzymes that are present in various tissues like penile tissue, platelets, vascular, and smooth muscle tissue. The drug's actions on these tissues have lead to the successful therapeutic use in patients suffering from conditions such as erectile dysfunction (ED) and pulmonary hypertension. PDE-5 inhibitors (PDE-5i) act on the erectile tissue causing penile smooth muscle relaxation and vasodilatation leading to penile erection. In addition, in particular when used in conjunction with prostaglandin inhibitors, PDE-5i cause vasodilatation in pulmonary vasculature hence decreasing both the pulmonary arterial pressure and resistance. PDE-5i have also shown to mildly decrease blood pressure, increase cardiac index, and increase coronary blood flow in experimental animals as well as in human studies. The Food and Drug Administration (FDA) has approved three PDE-5i for the treatment of ED: sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis) and one for pulmonary hypertension: sildenafil (Revatio). These agents are highly selective for PDE-5 enzymes as compared to other subclasses of PDE enzymes and have the almost identical pharmacological action but slightly different pharmacokinetics. Only little data exist about long-term use of PDE-5i and their effects on different organ system. This paper reviews the current information available on chronic PDE-5 inhibitor use.     

Erectile dysfunction in patients with coronary artery disease

Recent studies suggest that erectile dysfunction (ED) may be an early marker of endothelial dysfunction and coronary artery disease (CAD). Conversely, patients with CAD commonly have ED. The phosphodiesterase 5 (PDE5) inhibitors are very effective for the treatment of ED in patients with CAD. Numerous studies show that this class of drugs is in general safe in patients with stable CAD and these agents do not exacerbate ischemia in men with CAD undergoing exercise stress testing. Analysis of placebo-controlled trials did not show an increase in cardiovascular events among men receiving PDE5 inhibitors, and post-marketing surveillance studies with sildenafil did not observe an increase in cardiovascular events compared to expected age-matched rates. Organic nitrates remain a contraindication for PDE5 inhibitors and alpha blockers have precautions/contraindications depending upon specific drugs. The Princeton Consensus Guidelines (soon to be updated) suggest a logical approach to the patient with CAD seeking therapy for sexual dysfunction.     

Phosphodiesterase type 5 inhibitors for erectile dysfunction

The cyclic nucleotide signalling pathway mediates the smooth-muscle relaxing effects of nitric oxide necessary for normal erectile function. Down-regulation of this pathway is central to the pathophysiology of many forms of erectile dysfunction (ED), which is often associated with other chronic diseases (e.g. hypertension, type 2 diabetes mellitus) and treatments (e.g. certain drugs, radical prostatectomy). Conversely, selective inhibition of the enzyme that catalyses the degradation of cGMP (phosphodiesterase type 5, PDE-5) promotes erectile responses to sexual stimulation. The successful launch and commercialization of the selective PDE5 inhibitor (PDE5I) sildenafil transformed the treatment of ED, not only by providing an effective, well tolerated oral ED therapy, but also by fostering greater candour about the problem among men. Sildenafil is highly effective in promoting erectile responses across a wide spectrum of severity and causes of ED, including patients with ED that is often refractory to treatment. The recent advent of vardenafil, which has the highest in vitro potency of all available PDE5Is, and tadalafil, which has a prolonged half-life that may enable couples to have sexual activity with less planning, represent further advances. Other PDE5Is offering further potential improvements are under active investigation.     

Evolution of phosphodiesterase type 5 inhibitors in treatment of erectile dysfunction in Taiwan

Erectile dysfunction (ED) is a prevalent form of male sexual dysfunction. Phosphodiesterase type 5 (PDE5) inhibitor is the first-line treatment for ED. Numerous well-designed and -conducted clinical trials and postmarketing studies have established the safety and efficacy of PDE5 inhibitors for the treatment of ED. Ever since the first approval of sildenafil in 1998, PDE5 inhibitors have had several advances in their clinical use. More new agents with different pharmacokinetic profiles and new formulations were marketed. Conventional on-demand administration expanded to daily dosing. These advances provide more flexibility in clinical treatment of ED for patients and physicians. Moreover, clinical indications of PDE5 inhibitors extend from treatment of ED to pulmonary arterial hypertension and signs and symptoms of benign prostatic hyperplasia because of the distribution of PDE5 enzyme in human organs and tissues. The evolution of PDE5 inhibitors heralds a remarkable medical history from bench to clinical practice.     

PDE5 inhibitors beyond erectile dysfunction

The phosphodiesterase type-5 (PDE5) inhibitors sildenafil, vardenafil and tadalafil are widely used first-line therapy for erectile dysfunction (ED). Since the advent of sildenafil in 1998, more than 40 million men worldwide have been successfully treated with these compounds. The safety and high tolerability of PDE5 inhibitors make them an attractive tool to investigate further physiological functions of PDE5, for example the modulation of intracellular cyclic GMP (cGMP) pools. As cGMP is a key component of intracellular signaling this may provide novel therapeutic opportunities beyond ED even for indications in which chronic administration is necessary. The approval of sildenafil for the treatment of pulmonary hypertension in 2005 was a notable success in this area of research. A number of other potential new indications are currently in various phases of preclinical research and development. In recent years, extensive but very heterogeneous information has been published in this field. The aim of this review is to summarize existing preclinical and clinical knowledge and critically discuss the evidence to support potential future indications for PDE5 inhibitors.     

Tolerability and safety profile of sildenafil citrate (Viagra) in Latin American patient populations

Safety data from 546 men with erectile dysfunction (ED) enrolled in three double-blind, placebo-controlled studies conducted in distinct regions of Latin America were pooled and analyzed. The most commonly reported adverse events of all causalities associated with sildenafil treatment were headache (19%), flushing (14%), dyspepsia (6%), and nasal congestion (4%), reflecting the inhibitory effects of sildenafil on cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5) in the peripheral vasculature, gastroesophageal sphincter, and nasal mucosa. Visual symptoms were reported in 5.5%, reflecting sildenafil's minor inhibitory effects on cGMP-specific PDE6 in the retina. These adverse events were generally transient and mild, and rarely resulted in discontinuation of sildenafil therapy. Thus, in this representative sample of Latin American men with ED, including those with concomitant stable cardiovascular disease, sildenafil treatment was well tolerated with an incident rate of adverse events similar to reports from other patient populations.     

Molecular pharmacotherapeutic targeting of PDE5 for preservation of penile health

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.     

Phosphodiesterase type 5 inhibitors: the day after

OBJECTIVE: Review the literature on phosphodiesterase type 5 inhibitors (PDE5-Is), addressing critical issues in their current and future use, assessing unanswered questions, and identifying research needs. METHODS: A MEDLINE search was conducted on PDE5-Is, with emphasis on clinical trials and experience, for interpretation and analysis of their present and future role. RESULTS: Although approximately 40 million patients with erectile dysfunction have been treated successfully worldwide with the three available PDE5-Is, inappropriate instructions, lack of follow-up, and lack of patient-centered care models are the main reasons for "non-response," leading to drop-out rates of >50%. Patients with severe neurologic damage, diabetes mellitus, or severe vascular disease may be resistant to PDE5-Is. Preservation of corporal smooth muscle with chronic administration of PDE5-Is has been reported and substantial evidence indicates that these drugs have beneficial effects on endothelium and cardiovascular function; sildenafil has been approved for the treatment of idiopathic pulmonary hypertension. Improvement of lower urinary tract symptoms in men with benign prostatic hyperplasia after PDE5-I administration has been also suggested. CONCLUSIONS: The data indicate the necessity for (1) exploration of the pharmacologic characteristics of the three PDE5-Is; (2) research on their pharmacologic differences because some actions seems to be drug-specific; (3) development of alternative management strategies, such as chronic, low, everyday doses of PDE5-Is, if the monthly cost is affordable; and (4) clinical trials on use of PDE5-Is to treat other chronic conditions. The door for innovative therapeutic approaches will open, specifically for cross-risk factor treatment with PDE5-Is or their use in combination treatments or new multimodal pills that take advantage of drugs that exert pleiotropic vascular actions.     

Treating erectile dysfunction by endothelial rehabilitation with phosphodiesterase 5 inhibitors

A large body of evidence has accumulated demonstrating that a common pathway in conditions such as hypertension, atherosclerosis, hypercholesterolemia, diabetes mellitus, and erectile dysfunction (ED) is endothelial dysfunction. Although a complete pharmacological cure for ED is currently unavailable, the phosphodiesterase 5 (PDE5) inhibitors sildenafil, vardenafil, and tadalafil are efficacious oral therapy for ED. Results from recent studies suggest that regular treatment with a PDE5 inhibitor may lead to enhanced erectile function (EF) beyond that observed with on-demand usage, possibly through improvement of endothelial function. Such an effect may be viewed as rehabilitation of damaged erectile tissue. The present review focuses on several recent studies which provide evidence for the beneficial effect of regular PDE5 inhibitor administration on the improvement of EF by rehabilitation of vascular endothelium.     

Phosphodiesterase inhibitors in female sexual dysfunction

Based on the increasing knowledge on both the physiology of penile erection and the pathophysiology of erectile dysfunction, selective phosphodiesterase (PDE) inhibitors have been successfully introduced in the oral treatment of male erectile dysfunction. Because of their central role in smooth muscle tone regulation, PDEs remain an attractive target for drug development in urology. Since the distribution and functional significance of PDE isoenzymes vary in different tissues, selective inhibitors of the isoenzymes have the potential to exert at least partially specific effects on the target tissue. Currently, PDE inhibitors are under investigation with potential uses in urinary stone disease, overactive bladder and the so-called benign prostatic syndrome. The convincing clinical data on the use of the orally active PDE5 inhibitors sildenafil (VIAGRA), vardenafil (LEVITRA) and tadalafil (CIALIS) in the treatment of erectile dysfunction are accompanied by boosting research activities on intracellular signal transduction and PDE characterisation in female genital tissues with the aid of immunohistochemistry and immunocytochemistry and molecular biology. The expression of various PDE isoforms in the human clitoris, vagina and labia minora was shown by means of immunohistochemistry and RT-PCR analyses and it was concluded from functional studies that an increase in cGMP or cAMP might be involved in the regulation of female genital blood flow and the control of genital non-vascular smooth muscle. As a consequence, the efficacy and safety of the PDE5 inhibitor sildenafil in the treatment of symptoms of female sexual dysfunction (FSD), including female sexual arousal disorders (FSAD), have been evaluated. Although the experiences from these early clinical studies have so far not been conclusive, they suggest that, after appropriate evaluation of patients, inhibition of PDE5 might be of benefit for selected individuals with FSAD. Such research efforts will possibly allow the identification of efficacious and diagnostic tools for erectile dysfunction and of even more selective drugs in its therapy.     

Chronische PDE-5-Hemmung bei erektiler Dysfunktion

Erectile dysfunction (ED) is often associated with increased cardiovascular risk. There is increasing evidence suggesting that dysfunction of the vascular endothelium with reduced bioavailability of nitric oxide (NO) may be the pathogenetic link between ED and cardiovascular disease. The crucial importance of the NO-guanylatecyclase-cGMP-phosphodiesterase pathway for penile erection is mirrored by the efficacy of phosphodiesterase-5 (PDE5) inhibitors in the treatment of ED. In contrast to other currently available PDE5 inhibitors with a half-life time of about 4 h Tadalafil has a half-life time of about 17.5 h resulting in erectile responsiveness for up to 36 h after 1 single dose. Most clinical experience has been reported with on-demand use of PDE-5 inhibitors, but meanwhile several studies were able to demonstrate that Tadalafil given daily in low (2.5 and 5 mg) doses is both highly effective and well-tolerated. In three randomized, double-blind, placebo-controlled multi-center trials, various validated measures of erectile function indicated that once daily Tadalafil at doses of 2.5, 5, and 10 mg was significantly superior to placebo. In another mono-center trial, once daily Tadalafil has shown significant efficacy even after failure of on-demand treatment. In a controlled cross-over study of on-demand versus daily Tadalafil treatment, 72% of the patients preferred once daily administration, mainly because of superior and longer efficacy allowing a more spontaneous sexual life. Interestingly in a pilot study of on-demand versus chronic administration of Tadalafil for 4 weeks, only regular dosing improved several markers of endothelial function.     

Recent insights into androgen action on the anatomical and physiological substrate of penile erection

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)     

Hypogonadism and erectile dysfunction: the role for testosterone therapy

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.     

An open-label,multicenter, randomized,crossover study comparing sildenafil citrate and tadalafil for treating erectile dysfunction in Chinese men na?ve to phosphodiesterase 5 inhibitor therapy

The study was to compare treatment preference, efficacy, and tolerability of sildenafil citrate (sildenafil) and tadalafil for treating erectile dysfunction (ED) in Chinese men naïve to phosphodiesterase 5 (PDE5) inhibitor therapies. This multicenter, randomized, open-label, crossover study evaluated whether Chinese men with ED preferred 20-mg tadalafil or 100-mg sildenafil. After a 4 weeks baseline assessment, 383 eligible patients were randomized to sequential 20-mg tadalafil per 100-mg sildenafil or vice versa for 8 weeks respectively and then chose which treatment they preferred to take during the 8 weeks extension. Primary efficacy was measured by Question 1 of the PDE5 Inhibitor Treatment Preference Questionnaire (PITPQ). Secondary efficacy was analyzed by PITPQ Question 2, the International Index of Erectile Function (IIEF) erectile function (EF) domain, sexual encounter profile (SEP) Questions 2 and 3, and the Drug Attributes Questionnaire. Three hundred and fifty men (91%) completed the randomized treatment phase. Two hundred and forty-two per 350 (69.1%) patients preferred 20-mg tadalafil, and 108/350 (30.9%) preferred 100-mg sildenafil (P < 0.001) as their treatment in the 8 weeks extension. Ninety-two per 242 (38%) patients strongly preferred tadalafil and 37/108 (34.3%) strongly the preferred sildenafil. The SEP2 (penetration), SEP3 (successful intercourse), and IIEF-EF domain scores were improved in both tadalafil and sildenafil treatment groups. For patients who preferred tadalafil, getting an erection long after taking the medication was the most reported reason for tadalafil preference. The only treatment-emergent adverse event reported by > 2% of men was headache. After tadalafil and sildenafil treatments, more Chinese men with ED naïve to PDE5 inhibitor preferred tadalafil. Both sildenafil and tadalafil treatments were effective and safe.     

伐地那非的心血管安全性研究

伐地那非 (vardenafil,艾力达 )是新的选择性磷酸二酯酶 5型抑制剂 (PDE5I) ,通过选择性PDE5抑制作用(IC50 :0 .0 1nmol/L)而增强勃起功能 ,国际和国内临床研究已经表明其治疗勃起功能障碍 (ED)安全有效。艾力达和其他PDE5I一样由于具有轻度血管扩张作用 ,引起一过性头痛、头晕、颜面潮红、鼻塞等不良反应。本文对最近有关艾力达对心血管系统安全性的研究进行综述。研究显示 ,艾力达对处于心脏功能代偿期的心血管疾病患者、无活动性心绞痛或已控制好的冠心病患者ED治疗安全有效。治疗剂量的艾力达平均降低外周动脉血压幅度 <10mmHg ,除了与有机亚硝酸类药物具有协同降血压作用之外 ,与其他降压药物没有显著协同降血压作用。艾力达对心肌复极间期 (QTc)有轻微延长作用 ,但是目前临床研究没有发现艾力达引起的心律失常。 5项安慰剂对照的临床研究资料表明 ,服用艾力达后发生心血管不良事件的种类以及发生几率与安慰剂无显著差异。目前 ,研究结果表明 ,艾力达在临床治疗剂量下 ,对心血管功能具有较好的安全性和耐受性 ,是一种安全有效的治疗ED的一线药物。     

伐地那非治疗难治性勃起功能障碍的最新进展

5型磷酸二酯酶(phosphodiesterase 5,PDE5)在阴茎勃起功能中所起的作用越来越引起人们的关注。环磷酸鸟苷(cGMP)信号通路介导的一氧化氮平滑肌舒张效应是正常勃起功能的必要条件,这个信号通路的下调能引起勃起功能障碍(erectile dysfunction,ED)的许多病理状态,并导致一些慢性疾病的发生。本文回顾了伐地那非治疗ED患者的有效性和安全性。结果表明,伐地那非对于合并异常脂蛋白血症和高血压、糖尿病、抑郁症、前列腺切除术后、外伤性脊髓损伤、西地那非治疗无效、肾移植术后、慢性前列腺炎和早泄的ED患者安全有效,为这些难治性ED患者提供了一种合理的治疗选择。另外,伐地那非还能延长ED患者的勃起时间。     

Orange peels modulate antioxidant markers and key enzymes relevant to erection in the penile tissue of paroxetine‐treated rats

In comparison to other antidepressant drugs, erectile dysfunction (ED) is more pronounced in paroxetine use. On the other hand, orange (Citrus sinensis) peels commonly consumed in various forms are used in folkloric medicine for ED management. Thus, this study evaluated the effect of orange peels infusion on sexual behaviour, nitric oxide (NO) level and some enzymes (arginase, phosphodiesterase‐5 [PDE‐5], acetylcholinesterase [AChE] and adenosine deaminase [ADA]) in paroxetine‐treated rats. Erectile dysfunction was induced with paroxetine (10 mg/kg body weight). The animals were grouped into five (n = 6): normal rats; paroxetine‐induced rats; paroxetine‐induced rats treated with sildenafil citrate (5 mg/kg); paroxetine‐induced rats treated with orange peels infusion (50 mg/kg); Paroxetine induced rats treated with orange peel infusions (100 mg/kg). The results revealed a significant decrease in sexual behaviour, NO level and the activities of antioxidant enzymes, while there was a significant increase in arginase, PDE‐5, AChE and ADA activities in paroxetine‐induced rats. However, orange peel infusions ameliorated erectile dysfunction in paroxetine‐treated rats. This study showed some possible biochemical basis underlying the use of orange peels infusion in erectile dysfunction management.     

The effects of phosphodiesterase type 5 inhibitors on penile rigidity variables during a period with no sexual stimulation: a laboratory setting double‐blind study

Study Type – Therapy (RCT)
Level of Evidence 1b What’s known on the subject? and What does the study add? There is a positive effect of PDE5 inhibitors on several aspects of the men’s sex lives, chiefly erectile function, personal self‐esteem, and satisfaction from their sex lives. To our knowledge, our study is the first study to evaluate the effects of PDE5 inhibitors on erectile variables simultaneously in a laboratory setting. In the present study, significant penile rigidities were obtained with PDE5 inhibitors in a short period, with no sexual stimulation, in laboratory conditions. Our findings might support the use of PDE5 inhibitors in the men who need penile rehabilitation.

OBJECTIVE

To investigate the effects of phosphodiesterase type 5 (PDE5) inhibitors on erectile variables during a period with no sexual stimulation in a laboratory setting double‐blind study.

PATIENTS AND METHODS

In all, 80 men without erectile dysfunction (ED) but with lifelong premature ejaculation (PE) were included in the study. The men were divided equally in to four groups and received either placebo, vardenafil (10 mg), sildenafil (50 mg) or tadalafil (20 mg) in a double‐blind study design. The men attended the laboratory following 3 days of sexual abstinence and placebo or one of the PDE5 inhibitors was ingested after ≥2 h of fasting and non‐smoking. The men were then immediately placed in a silent room and real‐time penile rigidity and tumescence monitoring with Rigiscan Plus (Rigiscan Plus® System, Osbon Medical Systems, Augusta, GA, USA) began. The men read some magazines or newspapers that contained no sexually stimulating material for 1.5 h. There was no interaction between the men and observer during the test period. Times to first measured and total durations of base and tip rigidities, and also total and per minute rigidity were evaluated.

RESULTS

The recorded base and/or tip rigidity ratios were 40% (eight of 20), 71% (12/17), 47% (nine of 19) and 70% (14/20) in men who took placebo, sildenafil, tadalafil and vardenafil, respectively (P= 0.126). The ratio of men who could obtain ≥60% base and/or tip rigidities were 10% (two of 20), 41% (seven of 17), 26% (five of 19) and 55% (11/20) in placebo, sildenafil, tadalafil and vardenafil groups, respectively (P < 0.05). The median time to first measured base rigidity was 58.0, 21.5, 54.5 and 57 min with placebo, sildenafil, tadalafil and vardenafil, respectively (P= 0032). The median total duration of recorded base rigidity was 4.0, 27.5, 10.0 and 11.5 min in men who took placebo, sildenafil, tadalafil and vardenafil, respectively (P= 0.013). The median total base rigidity (area under the curve) was 72.8, 699.0, 360.5 and 553.0 with placebo, sildenafil, tadalafil and vardenafil, respectively (P= 0.016).

CONCLUSIONS

Significant penile rigidities were obtained with PDE5 inhibitors during the short test period, with no sexual stimulation, in laboratory conditions. This finding might support the use of PDE5 inhibitors in men who need penile rehabilitation.