Phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction in patients with diabetes mellitus

Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, has become a first-line therapy for diabetic patients with erectile dysfunction (ED). The efficacy in this subgroup, based on the Global Efficacy Question, is 56% vs 84% in a selected group of non-diabetic men with ED. Two novel PDE5 inhibitors, tadalafil (Lilly ICOS) and vardenafil (Bayer), have recently completed efficacy and safety clinical trials in 'general' and diabetic study populations and are now candidates for US FDA approval. A summary analysis of the phase three clinical trials of sildenafil, tadalafil and vardenafil in both study populations is presented to provide a foundation on which the evaluation of the role of the individual PDE5 inhibitors for the treatment of patients with ED and DM can be built.     

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.     

An open-label, multicentre, randomized, crossover study comparing sildenafil citrate and tadalafil for treating erectile dysfunction in men naïve to phosphodiesterase 5 inhibitor therapy

Associate Editor Michael G. Wylie Editorial Board Ian Eardley, UK Jean Fourcroy, USA Sidney Glina, Brazil Julia Heiman, USA Chris McMahon, Australia Bob Millar, UK Alvaro Morales, Canada Michael Perelman, USA Marcel Waldinger, Netherlands

OBJECTIVES

To compare treatment preference, efficacy, and tolerability of sildenafil citrate (sildenafil) and tadalafil for treating erectile dysfunction (ED) in men naïve to phosphodiesterase 5 (PDE5) inhibitor therapy.

PATIENTS AND METHODS

This was an open‐label, crossover study of sildenafil and tadalafil (taken as needed). After a 4‐week baseline assessment, 367 men with ED (mean age 54 years) were randomized to receive sildenafil for 12 weeks followed by tadalafil for 12 weeks or vice versa (8‐week dose optimization and 4‐week assessment phases). During dose optimization, patients started taking 25‐ or 50‐mg sildenafil or 10‐mg tadalafil and could titrate to find their optimum dose (25‐, 50‐ or 100‐mg sildenafil; 10‐ or 20‐mg tadalafil). After completing both 12‐week periods, patients chose which treatment to continue during an 8‐week extension. Efficacy was measured with the International Index of Erectile Function (IIEF) and Sexual Encounter Profile (SEP) diary.

RESULTS

Of the 291 men who completed both treatments, 85 (29%) chose sildenafil and 206 (71%) chose tadalafil (P < 0.001) for the 8‐week extension. The IIEF erectile function domain scores were 14.2 at baseline, 23.9 at endpoint on sildenafil, and 24.3 at endpoint on tadalafil (P = 0.08, sildenafil vs tadalafil). The mean per patient percentage success scores for SEP2 (penetration) were: baseline (46%), sildenafil (post‐baseline 82%) and tadalafil (post‐baseline 85%; P = 0.06, sildenafil vs tadalafil), and for SEP3 (successful intercourse) were: baseline (19%), sildenafil (post‐baseline 72%), and tadalafil (post‐baseline 77%; P = 0.003, sildenafil vs tadalafil). The only treatment‐emergent adverse events that were reported by >5% of men were headache and flushing.

CONCLUSIONS

In men with ED who were naïve to PDE5 inhibitor therapy, sildenafil and tadalafil were both effective and well tolerated. After treatment with sildenafil and tadalafil, 29% of men chose sildenafil and 71% chose tadalafil for ED therapy during an 8‐week extension.

     

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.     

Therapeutic effectiveness and patient satisfaction after 6 months of treatment with tadalafil, sildenafil, and vardenafil: results from the erectile dysfunction observational study (EDOS)

OBJECTIVE: This observational study was conducted across Europe to assess health outcomes in men with erectile dysfunction (ED) who took tadalafil, sildenafil citrate (sildenafil), or vardenafil HCl (vardenafil) for 6 mo. METHODS: Therapy effectiveness and patient satisfaction were evaluated using established and new questions on erectile function. Behavioural, psychological, and relationship outcomes were assessed using the short form of the Psychological and Interpersonal Relationship Scales (SF-PAIRS). RESULTS: In nine European countries at 904 sites, 8047 patients were enrolled and 94% (7560) selected either tadalafil (5315), sildenafil (1252), or vardenafil (993) for treatment at baseline. Of the 7560, 3998 (52.9%) took the same drug for 6 mo. Baseline characteristics across the three treatment groups were comparable: mean age approximately 56 yr, moderate or severe ED, and mean International Index of Erectile Function-Erectile Function domain score about 13. Tadalafil, sildenafil, and vardenafil were therapeutically effective and improved patient satisfaction in the 40-58% of men who completed 6 mo of a single therapy. Patients taking tadalafil consistently had numerically higher levels of therapeutic effectiveness and satisfaction compared with patients who took sildenafil or vardenafil. The three cohorts had statistically significant changes from baseline in response to SF-PAIRS and there were significant differences, in favour of tadalafil, among cohorts in the Time Concerns domain. CONCLUSION: In a large observational study that mimics a routine clinical setting, most patients selected an inhibitor of phosphodiesterase 5 to treat ED, which resulted in a high level of therapeutic effectiveness and patient satisfaction.     

Drug Insight: oral phosphodiesterase type 5 inhibitors for erectile dysfunction

Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men. At present, first-line oral pharmacotherapy for most patients with ED is a phosphodiesterase type 5 (PDE-5) inhibitor, of which three are currently available worldwide. Sildenafil (Viagra, Pfizer) has a very satisfactory efficacy-safety profile in all patient categories. The first PDE-5 inhibitor to reach the market, it is now the most widely prescribed oral agent for ED. Tadalafil (Cialis, Lilly ICOS) and vardenafil (Levitra, Bayer/GlaxoSmithKline) were introduced to the European Union and the US in 2003 and 2004, respectively. These three PDE-5 inhibitors share many characteristics, but each has unique features. This review describes the chemical, pharmacologic and clinical features of sildenafil, vardenafil and tadalafil as oral first-line treatments for ED. First, we describe the physiology of penile erection and PDE-5 inhibitor pharmacology, including chemistry, PDE selectivity, pharmacokinetics, and possible drug interactions. We then summarize data on the efficacy and safety profiles of the three PDE-5 inhibitors for the treatment of ED in the general population, in patients with diabetes mellitus and in men that have undergone bilateral nerve-sparing retropubic radical prostatectomy.     

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.     

Erektile Dysfunktion

Erectile dysfunction (ED) tends to be associated with other diseases, the common basis of which is endothelial dysfunction. ED is also frequently combined with LUTS and the common basis for both conditions seems to be elevation of Rho-kinase activity and decrease of NO concentration. Because all three PDE 5 inhibitors sildenafil, tadalafil, and vardenafil have a common mode of action, i.e., inhibition of PDE 5, they are not different in terms of their efficacy and safety profile except for color vision disturbances which are more common after sildenafil and back pain/myalgia more often observed after tadalafil. The main differentiating characteristics among the three PDE 5 inhibitors are their pharmacokinetics. These are ultimately responsible for the observation that in head-to-head comparative trials depending on the respective study design the overwhelming majority of the patients opted either for tadalafil as the longest acting PDE 5 inhibitor (36 h) or for vardenafil as a relatively rapidly acting drug.All published studies so far have shown that in terms of the cardiovascular risk profile (myocardial infarction rate) all three PDE 5 inhibitors performed better than placebo although the results were not statistically significant. Without any exception it applies to all three PDE 5 inhibitors that they are absolutely contraindicated in patients taking nitrate- or molsidomine-containing medications and that they may interact in particular with non-uroselective alpha-adrenoceptor blockers. This is why their simultaneous application with PDE 5 inhibitors has to be avoided.In the near future chronic (daily) application of a PDE 5 inhibitor may show advantages, at least in those 50-60% of all patients in whom there is a high likelihood of endothelial dysfunction due to the diagnostic (penile duplex Doppler) outcome. Possible new developments in the management of ED with a time frame of 5-8 years until their market approval are guanylate cyclase activators, Rho-kinase inhibitors, melanocortin receptor agonists, gene therapy, and tissue engineering.     

Do vardenafil and tadalafil have advantages over sildenafil in the treatment of erectile dysfunction?

Erectile dysfunction (ED) affects up to 50% of men between the ages of 40 and 70 years of age. Sildenafil, vardenafil and tadalafil have all been shown to be similarly effective in the treatment of men with ED of vary etiologies, to have similar adverse effects profiles, and to improve quality-of-life by similar amounts. As these phosphodiesterase 5 (PDE5) inhibitors all increase the hypotensive effects of nitrates, they are not suitable for use in patients taking nitrates for the treatment of ischaemic heart disease. All three inhibitors must be used with caution in patients taking alpha(1)-adrenoceptors antagonists for benign prostatic hyperplasia. Although nonarteritic anterior ischaemic neuropathy has been reported in some users of the PDE5 inhibitors, there is no conclusive evidence that PDE5 inhibitors cause this rare effect. Tadalafil has a longer half-life than sildenafil or vardenafil, and a longer duration of action than sildenafil and vardenafil. Most preference studies have shown tadalafil to be preferred, but there are serious limitations to some of these studies. One approach to treatment is to give each patient a short- and long-acting agent, and for individuals to decide their preference.     

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.     

同期内使用3种PDE5抑制剂治疗ED的经验

目的:观察与比较同期内使用3种PDE5抑制剂治疗ED患者的疗效,满意情况和不良反应。分析影响患者疗效、接受度、倾向性的因素。方法:11个月在门诊应用3种PDE5抑制剂治疗ED患者331例。使用西地那非134例,他达拉非88例,及伐地那非109例。医师详细指导药物的应用,注意事项,观察的内容等,并互留电话,列表登记、随访。结果:复诊或电话随访时间,结果为:①获得良好的疗效及满意率为西地那非72例(79.12%),他达拉非52例(78.78%),伐地那非63例(81.81%)。②PDE5抑制剂单纯或交叉应用的资料分析显示:青年患者或新婚者,偏好伐地那非;③中青年患者倾向于他达拉非;中老年及较长期应用PDE5抑制剂的患者多选用西地那非。3种PDE5抑制剂用于早泄均有一定疗效。④对不能继续用此类药治疗ED的原因进行了分析,分别为:价高,不治本,效果差,耽心不良反应。结论:①同期3种PDE5抑制剂治疗ED的疗效基本相近。亦各有一些优势和特点。②3种PDE5抑制剂的安全性均好,一般、轻度不良反应相近,中度、特殊的不良反应少,严重不良反应均无发生。③PDE5抑制剂的疗效观察,目前众多的问卷、量表实际均仍以主观的感受为主。对同一个人以相同形式、相同问题、繁简一致阐述,获得的有关疗效满意情况、感受等简易回答是有可比性、可信度和实用性的。     

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.     

The effects of three phosphodiesterase type 5 inhibitors on ejaculation latency time in lifelong premature ejaculators: a double-blind laboratory setting study

Study Type – Therapy (RCT)
Level of Evidence 1b What’s known on the subject? and What does the study add? Several authors have reported their experience with PDE5 inhibitors alone or in combination with selective serotonin re‐uptake inhibitors for treating premature ejaculation. However, to our knowledge, this is the first laboratory design study to evaluate the effects of three PDE5 inhibitors throughout the ejaculation process in men with lifelong premature ejaculation. In this laboratory setting study PDE5 inhibitors seem to prolong ELT but the difference from placebo is significant only in vardenafil. The quality of penile rigidity is better with PDE5 inhibitors in the post‐ejaculatory period but the difference is significant only in sildenafil and vardenafil.

OBJECTIVE

? To evaluate the effects of three phosphodiesterase type 5 (PDE5) inhibitors on the ejaculation process in men with lifelong premature ejaculation using a double‐blind laboratory setting.

PATIENTS AND METHODS

? Eighty men with lifelong premature ejaculation, 20 in each group, received placebo, vardenafil (10 mg), sildenafil (50 mg) or tadalafil (20 mg) in a double‐blind study design. Placebo or PDE5 inhibitor was ingested after at least 2 h fasting and non‐smoking. The subjects were placed in a silent room immediately and real‐time penile rigidity and tumescence was monitored. ? Subjects read some magazines or newspapers without any sexually stimulating material for 1.5 h. At the end of this period audiovisual sexual stimulation began with a video film and after the 8th minute the subject began vibratory stimulation to the frenular area. ? At the beginning of ejaculation the patient stopped stimulation. When the patient began and stopped stimulation, the light near the observer turned on and off and the observer calculated the ejaculation period with a chronometer. The elapsed time was the ejaculation latency time (ELT) in seconds. ? There was no interaction between subjects and observer during the test. The ELT, and the qualities of base and tip rigidities during ELT and after ejaculation were calculated.

RESULTS

? Median age of patients was 29 (range 22–39) years and median duration of premature ejaculation was 60 (range 7–180) months and there was no significant difference between groups. Median duration of vibratory stimulation (ELT) of subjects who received placebo was 48.5 s: 53.5 s for sildenafil, 70.0 s for tadalafil and 82.5 s for vardenafil. Compared with the placebo group, ELT was significantly longer only in subjects receiving vardenafil (P = 0.019). ? In the post‐ejaculatory refractory period, times to last recorded base rigidities were significantly longer than placebo in vardenafil and sildenafil groups with better erection quality (P < 0.01 for each).

CONCLUSIONS

? The PDE5 inhibitors seem to prolong ELT and the quality of penile rigidity is better with PDE5 inhibitors in post‐ejaculatory period. ? These findings suggest that PDE5 inhibitors might have some beneficial effects in men with lifelong premature ejaculation.     

Evidence for contamination of herbal erectile dysfunction products with phosphodiesterase type 5 inhibitors

PURPOSE: We determined if pharmacological dosages of phosphodiesterase type 5 inhibitors (PDE5) inhibitors were present within a group of natural products marketed for the treatment of erectile dysfunction. MATERIALS AND METHODS: Seven herbal products marketed for the treatment of erectile dysfunction were purchased via the Internet or at local health food stores. Specimens were batched, relabeled and blindly analyzed for contamination with PDE5 inhibitors. High performance liquid chromatography and mass spectrometry were used to detect evidence of contamination with sildenafil, tadalafil or vardenafil. RESULTS: Of the 7 tested products 2 contained pharmacological dosages of sildenafil and tadalafil. Contamination with vardenafil was not identified. Mean dosages of sildenafil and tadalafil were 30.2 and 19.7 mg, respectively. CONCLUSIONS: A significant proportion of natural products marketed for erectile dysfunction contains PDE5 inhibitors. Although marketed as natural products devoid of adverse effects, these agents are known to have potentially fatal drug interactions with nitrates. Better regulation of the natural health products industry is urged.     

Efficacy and satisfaction rates of oral PDE5is in the treatment of erectile dysfunction secondary to spinal cord injury: a review of literature

Concept

Decreased sexual function is a major concern of men with spinal cord injuries (SCIs). Treatment of erectile dysfunction (ED) through oral pharmacotherapies has been proven to be an effective way to address and treat this concern.

Objective

To find an efficacious and satisfactory treatment ED secondary to SCI through the compilation of studies that utilized the International Index of Erectile Function (IIEF) when testing phosphodiesterase V inhibitors (PDE5i).

Method

Ten articles, which used the IIEF to study satisfaction and/or efficacy of PDE5is sildenafil, tadalafil, and vardenafil in the treatment of ED were reviewed and analyzed. Through the use of a self-made grading scale the value of each article was determined for this research.

Results

Sildenafil, tadalafil, and vardenafil all have been proven to be effective in treating ED in men with SCI. While sildenafil is the most thoroughly studied ED treatment for patients with SCI, tadalafil has a longer time duration effectiveness, which allows for more spontaneity in the sexual experience. Minimal adverse effects have been noted in patients with SCI using these medications; headache, flushing, and mild hypotension are the most common. In articles that study satisfaction, patients show great improvement over baseline with the use of these medications.

Conclusion

Although there is a need for further research on the safety in long-term use of tadalafil and vardenafil, comparative studies done on all three medications show no statistically significant difference in effectiveness or satisfaction. New medications and treatment options, such as avanafil, are being studied in hope of continued improvement of sexual function in men with SCI.     

伐地那非在难治性ED人群中的应用

本文回顾了高选择性口服磷酸二酯酶5(PDE5)抑制剂伐地那非在各种难治性ED人群的疗效和安全性。结果表明,伐地那非对于合并糖尿病、抑郁症、前列腺切除术后、外伤性脊髓损伤性、以及西地那非治疗无效的ED患者安全有效,为这些难治性ED人群提供了一种合理的治疗选择。     

Treatment preferences in men with erectile dysfunction： an open label study in Korean men switching from sildenafil citrate to tadalafil

To evaluate patient preferences for sildenafil citrate or tadalafil （PDE-5 inhibitors available for the treatment of erectile dysfunction [ED]） and assess potential reasons for these preferences. Methods： This open-label study was conducted on Korean men taking sildenafil, at least 6 weeks prior to study entry, for ED. Following screening, patients continued sildenafil treatment for 4 weeks, then after a 1-week washout period, switched to tadalafil for 8 weeks. Patients then continued with their treatment of choice during an extension phase. Psychosocial factors （time concern, spontaneity, sexual self-confidence） were evaluated using Psychological and Interpersonal Relation- ship Scales （PAIRS）, while timing of dose to sexual attempt patterns were assessed from patient diaries. Results： The present study enrolled 160 Korean men （mean age 55 years） with prior median sildenafil use of 585 days. During the extension phase, 73.7% of patients elected to take tadalafil, whereas 26.3% chose sildenafil （P 〈 0.001）. After switching from sildenafil to tadalafil, mean PAIRS time concern scores decreased from 2.54 to 2.42 （P = 0.002）, with no statistically significant differences observed between the sildenafil and tadalafil assessment phases in sexual spontaneity and self-confidence scores. Sexual attempts made 〉 4 h to 〈 36 h post-dose occurred in 4.5% of patients during the sildenafil assessment phase compared with 17.5% during the tadalafil assessment phase. Conclusion： After experiencing both sildenafil and tadalafil, the majority of patients exhibited a preference for tadalafil. This preference might be influenced by psychosocial factors, such as decreased time concerns, and a broader window of opportunity available for sexual activity.