Continuation and effectiveness of tadalafil once daily during a 6-month observational study in erectile dysfunction: the EDATE study.

AIMS: This was the first observational study evaluating treatment continuation, effectiveness and tolerability of tadalafil 5 mg once daily (TAD-OaD) in patients who chose and paid for treatment of erectile dysfunction (ED) in routine clinical practice. METHODS: Men ≥ 18 years with ED, treated previously with phosphodiesterase type 5 (PDE5)-inhibitor on-demand (PRN) or treatment-naïve, were enrolled at 59 sites. For patients prescribed TAD-OaD at baseline (T1), change in erectile function (IIEF-EF and GAQ) was documented after 1-3 (T2) and 4-6 (T3) months. The primary outcome was the probability to switch/discontinue from TAD-OaD, estimated by Kaplan-Meier (KM) product-limit method. Changes in IIEF-EF were evaluated using a mixed model for repeated measures adjusting for patient baseline characteristics. RESULTS: Of 975 men enrolled (median age 56.8 years, 33.7% with previous PDE5-inhibitor use), 778 were prescribed TAD-OaD, 135 TAD-PRN and 62 sildenafil or vardenafil PRN. During the 6-month longitudinal observation, 107 patients (13.8% of 778) switched or discontinued TAD-OaD-treatment. KM-rates (95%CI) for continuing TAD-OaD at 2, 4 and 6 months were 94.0% (92.3, 95.7), 88.3% (85.9, 90.6) and 86.3% (83.7, 88.9), respectively. The 25th percentile of time to switch/discontinuation of TAD-OaD was estimated as 31.1 weeks (lower 95%CI 30.3 weeks). At T3, IIEF-EF scores had increased by 7.1 (LSmean; 95%CI 5.8, 8.5) points; 91.3% of patients reported improved erections. The most frequently reported AE was headache (10 patients; 1.3%); no new/unexpected safety signals were observed. CONCLUSION: Under routine conditions, and when patients were involved in treatment decision-making, more than 86% of men starting/switching to tadalafil once daily (OaD) at baseline continued tadalafil OaD treatment for ≥ 6 months.

Psychosocial outcomes after initial treatment of erectile dysfunction with tadalafil once daily, tadalafil on demand or sildenafil citrate on demand: results from a randomized, open-label study.

Initiation of ED treatment with a particular PDE5I may influence treatment-adherence and other outcomes. In this multicenter, open-label study, men with ED, naïve to PDE5I, were randomized to tadalafil 5 mg once-a-day (OaD; N=257), 10 mg on demand (PRN; N = 252) or sildenafil-citrate (sildenafil) 50 mg PRN (N = 261) for 8 weeks (dose adjustments allowed), followed by 16 weeks of pragmatic treatment (switching between PDE5I allowed). Primary outcomes (treatment-adherence) were reported previously. Here, we report effects on: Psychological and Interpersonal Relationship Scales, Self-Esteem and Relationship (SEAR) questionnaire, ED Inventory of Treatment Satisfaction (EDITS), International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP) and Global Assessment Questions (GAQ). Mixed-model for repeated measures and analysis of covariance were used to analyze changes from baseline; GAQ-responses were evaluated by logistic regression. Analyses were adjusted for treatment, country, ED-severity, baseline and baseline-by-treatment interaction. Patients randomized to tadalafil OaD or PRN reported greater improvement (least-square mean (s.e.) change) in Sexual Self-Confidence (OaD +0.90 (0.048), PRN +0.93 (0.050), vs +0.73 (0.049); P=0.006 and P=0.001) and Spontaneity (OaD +0.11 (0.035), PRN +0.13 (0.035), vs +0.02 (0.035); P = 0.044 and P = 0.010) compared with sildenafil. Improvements in GAQ and SEP responses, IIEF-EF, orgasmic function, sexual desire, overall satisfaction domains, SEAR and EDITS scores did not differ significantly between treatment groups.

The assessment of vascular risk in men with erectile dysfunction: the role of the cardiologist and general physician.

Erectile dysfunction (ED) and cardiovascular disease (CVD) share risk factors and frequently coexist, with endothelial dysfunction believed to be the pathophysiologic link. ED is common, affecting more than 70% of men with known CVD. In addition, clinical studies have demonstrated that ED in men with no known CVD often precedes a CVD event by 2-5 years. ED severity has been correlated with increasing plaque burden in patients with coronary artery disease. ED is an independent marker of increased CVD risk including all-cause and especially CVD mortality, particularly in men aged 30-60 years. Thus, ED identifies a window of opportunity for CVD risk mitigation. We recommend that a thorough history, physical exam (including visceral adiposity), assessment of ED severity and duration and evaluation including fasting plasma glucose, lipids, resting electrocardiogram, family history, lifestyle factors, serum creatinine (estimated glomerular filtration rate) and albumin:creatinine ratio, and determination of the presence or absence of the metabolic syndrome be performed to characterise cardiovascular risk in all men with ED. Assessment of testosterone levels should also be considered and biomarkers may help to further quantify risk, even though their roles in development of CVD have not been firmly established. Finally, we recommend that a question about ED be included in assessment of CVD risk in all men and be added to CVD risk assessment guidelines.

Improvements in confidence, sexual relationship and satisfaction measures: results of a randomized trial of tadalafil 5 mg taken once daily.

An efficacy study of tadalafil (5 mg once daily) for treating erectile dysfunction included sexual satisfaction and psychosocial outcome measures such as Treatment satisfaction (THX) domain of Sexual Life Quality Questionnaire, Self-Esteem And Relationship (SEAR) questionnaire, Sexual Encounter Profile questions 4 (SEP4; hardness satisfaction) and 5 (SEP5; overall satisfaction), intercourse satisfaction (IS) and overall satisfaction (OS) domains of International Index of Erectile Function (IIEF), and partner SEP question 3 (pSEP3). After a 4-week run-in phase, participants were randomized to receive either tadalafil (N=264) or placebo (N=78) for 12 weeks. Participants and partners were more satisfied (THX) with tadalafil (75 and 73, respectively) than with placebo (51 and 55, respectively, P<0.001). Statistically significant improvements in sexual relationship, confidence, self-esteem and overall relationship (SEAR), in addition to IS, OS, SEP5 and pSEP3 for tadalafil compared with placebo (P<0.001) correlated with erectile function (EF) improvement (assessed by change from baseline in IIEF-EF score). Tadalafil significantly improved treatment and sexual satisfaction, while improving multiple outcomes measured by SEAR.

Efficacy of tadalafil once daily in men with diabetes mellitus and erectile dysfunction.

AIMS: Erectile dysfunction (ED) is a common comorbidity in men with diabetes mellitus. Tadalafil 10 or 20 mg taken on demand is efficacious and safe for men with diabetes and ED. Recently, continuous treatment with tadalafil has been proposed, addressing ED management as any other chronic condition. This study examined whether once-daily tadalafil 2.5 and 5 mg is efficacious for men with diabetes and ED. METHODS: This randomized, double-blind, placebo-controlled, multicentre, 12-week study enrolled 298 men with diabetes and ED to once-daily treatment with placebo, tadalafil 2.5 mg or tadalafil 5 mg. Primary efficacy measures were International Index of Erectile Function Erectile Function (IIEF EF) Domain score, and patient success rates for vaginal penetration and completion of intercourse. Patient satisfaction, endothelial function biomarkers, and safety were also assessed. RESULTS: Patients receiving either dose of tadalafil had clinically and statistically significant improvements in IIEF EF and statistically significant improvements in mean success rates for vaginal penetration, completion of intercourse, and overall treatment satisfaction (P < or = 0.005 tadalafil vs. placebo, all measures). Endothelial dysfunction biomarkers were unchanged. The most common adverse events were headache, back pain and dyspepsia. CONCLUSIONS: In this first study of men with diabetes and ED, once-daily tadalafil 2.5 and 5 mg was efficacious and well tolerated, suggesting this may be an alternative to on-demand treatment for some men, eliminating the need to plan sex within a limited timeframe.

Integrating partners into erectile dysfunction treatment: improving the sexual experience for the couple.

INTRODUCTION: Erectile dysfunction (ED) is a common condition estimated to affect more than 150 million men worldwide. ED should be regarded as a shared sexual problem which has significant detrimental effects both on the men who experience this condition and on their partners. EVIDENCE TO SUPPORT PARTNER INVOLVEMENT IN ED THERAPY: Evidence shows that the partner plays a key supportive role in the man's ED treatment and in successful long-term ED therapy. Including the partner in consultations may highlight discordant attitudes and communication problems between couple members which may indicate treatment acceptance or rejection, or realistic or unrealistic treatment expectations. OPTIONS FOR PARTNER INVOLVEMENT IN ED THERAPY: Most patients with ED consult their physician in the absence of their partner. Therefore, involving the partner in therapy can be challenging. Two options which physicians should consider are: encouraging the patient to bring the partner into the office and, often more realistically, seeking information about, and providing information to, the partner, via the patient. OBJECTIVES: The objective of these recommendations is to provide practical guidance on treating couples affected by ED, and suggest techniques that may be helpful in integrating the partner into the process of ED treatment.

The evolving role of testosterone in the treatment of erectile dysfunction.

Hypogonadism may play a significant role in the pathophysiology of erectile dysfunction (ED). A threshold level of testosterone may be necessary for normal erectile function. Testosterone replacement therapy is indicated in hypogonadal patients and is beneficial in patients with ED and hypogonadism. Monotherapy with testosterone for ED is of limited effectiveness and may be most promising in young patients with hypogonadism and without vascular risk factors for ED. A number of laboratory and human studies have shown the combination of testosterone and other ED treatments, such as phosphodiesterase type 5 (PDE5) inhibitors, to be beneficial in patients with ED and hypogonadism, who fail PDE5 inhibitor therapy alone. There is increasing evidence that combination therapy is effective in treating the symptoms of ED in patients for whom treatment failed with testosterone or PDE5 inhibitors alone. Testosterone replacement therapy has potentially evolved from a monotherapy for ED in cases of low testosterone, to a combination therapy with PDE5 inhibitors. Screening for hypogonadism may be useful in men with ED who fail prior PDE5 inhibitors, especially in populations at risk for hypogonadism such as type 2 diabetes and the metabolic syndrome.

Hyperprolactinemia and sexual function in men: a short review.

Erectile dysfunction (ED), generally associated with reduced sexual desire and sometimes with orgasmic or ejaculatory dysfunction, is the major revealing symptom of hyperprolactinemia (HPRL) in men, a condition that should not be neglected since many cases result from pituitary tumors, likely to result in serious complications. It is generally believed that the mechanism of the prolactin (PRL)-induced sexual dysfunctions is a decrease in testosterone secretion. In fact, serum testosterone is normal in many hyperprolactinemic males and there are also testosterone-independent mechanisms, probably mainly set at the level of the brain's neurotransmitter systems. Systematic determinations of serum PRL found very low prevalences of marked HPRL (>35 ng/ml) in ED patients (0.76% in a compilation of over 3200 patients) as well as of pituitary adenomas (0.4%). In addition, the association of HPRL with ED may have been coincidental in some of these cases, since 10% of the HPRLs diagnosed by the usual immunological assays are composed of macroprolactins, which are biologically inactive or little active variants of PRL. Their identification requires a PRL chromatography that is restricted to some specialized laboratories. There is presently no consensus with regards to the screening for HPRL in ED: systematic determination of serum PRL may be justified since HPRL is a serious but reversible disease, while there is presently no reliable clinical, psychometric or hormonal criteria (including serum testosterone level) allowing to restrict its determination to certain categories of the ED patients without risk of neglecting some HPRLs. In case of consistent HPRL, searching for a hypothalamic or pituitary tumor is mandatory. Dopamine-agonist therapy is the first choice treatment for the PRL-induced sexual dysfunctions. Additional sexual counselling may be necessary for certain patients.

Acceptance, efficacy and preference of Sildenafil in patients on long term auto-intracavernosal therapy: a study with follow-up at one year.

PURPOSE: To assess the acceptance, long term efficacy and preference of Sildenafil in impotent patients previously on auto-intracavernosal therapy. MATERIALS AND METHODS: The patients were the 107 men (mean age 58.4 y) on auto-intracavernosal therapy (auto-IC) for more than 6 months (mean duration 32.7 months >12 months in 100) who were consecutively seen within 6 months of the launch of Sildenafil in France. If there was no contra-indications to Sildenafil they were proposed a trial of Sildenafil at home. Following this trial they were given the possibility to change their therapy and were followed for 1 y at 3 months intervals. RESULTS: Three patients had contra-indications to Sildenafil. Of the remaining 104, 45 (43%) refused the trial, mainly because they were afraid of possible cardiac risks (n=21, including 51% of the psychogenic and mixed patients compared to 8% of the predominantly organic ones). Among the 59 who tried it, Sildenafil gave good results in 46 (78%), including 100% of the predominantly psychogenic and 61.5% of the predominantly organic ones) with minimum effective doses of 25 mg in 7, 50 mg in 18 and 100 mg in 21. It failed in 9 (15%) and gave average results in 4 (penetration with a non fully satisfying erection). There was a clear relationship between the sensitivity to Sildenafil and that to Alprostadil, the vasoactive agent predominantly used for the auto-ICIs. Every 46 patients with good result of Sildenafil elected to continue with this drug, including 3 who used both Sildenafil and auto-ICIs in alternance. Every 4 patients with average results elected to continue with auto-ICI including 1 who also used Sildenafil in alternance. Five of the 50 patients with good or average results were lost to follow-up within 6 months. At the 1 y follow-up visit, 43 of the 45 others were still using Sildenafil, in alternance with auto-ICI in 1. No one reported a decrease in efficacy with time. The 2 patients with average results still in the study were on auto-ICIs. CONCLUSION: Sildenafil is highly effective in the impotent men previously treated with auto-ICI and its efficacy is maintained at least for 1 y. When tried and effective it is preferred by most men but almost half of our patients refused trying it.

[Sexuality of the diabetic woman]. / La sexualité de la femme diabétique.

Diabetes Mellitus frankly increases the prevalence of sexual problems in men, mainly in the form of erectile dysfunctions. Its effects on sexual function of the diabetic women have been less objectively studied, due to cultural reasons and methodological difficulties. The different phases of the sexual cycle, as well as their physiological control, are similar in human males and females. Several studies suggest an increased prevalence of sexual problems also in diabetic females. Their rate seems similar to that of the males. An increased prevalence of Female Sexual Arousal Disorder has been found in 6 studies of 6 comparing diabetic to non diabetic females. Its main symptom was a deficient vaginal lubrication, making sexual intercourse unpleasant. This disorder is the female equivalent to erectile dysfunction. It probably results from similar mechanisms, involving damages in the vascular and autonomic nervous systems, as well as alteration in the nitric oxide production and efficacy. The prevalence of Hypoactive Sexual Desire Disorder was also increased in most studies (5 of 8, significantly in 3). This could result from the increased prevalence of depression in diabetic females. The Dyspareunia's prevalence was not significantly increased (0 of 6 studies). Available figures are not consistent as regards the orgasmic disorders (prevalence increased in only 4 of 8 studies). No significant correlation of female sexual dysfunction with diabetes duration, balance, or complications has been found. Conversely some significant correlations with depression or poor acceptance of diabetes have been found, supporting a causative role of psychological factors. Although still limited the therapeutic options should not be neglected. Merely prescribing a water soluble lubricating gel may greatly improve the sexual life of couples. Doctors should talk themselves about sexual function with their female diabetic patients. Most of these are too much embarrassed to ask themselves their doctor, although their sexual problems may seriously interfere with their quality of life and that of their partner.