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<blockquote data-quote="madman" data-source="post: 242300" data-attributes="member: 13851"><p>Guess those Italians who are at the top of their game when it comes to men's sexual health have no clue what the f**k they are talking about!</p><p></p><p>2022!</p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/forum/threads/erectile-dysfunction-medical-therapy-and-rehabilitation.26341/[/URL]</p><p></p><p><strong>4.1.1.2 The Right Molecule for the Right Patient </strong></p><p></p><p><em><strong>The choice of the best PDE-5Is is not supported by any double or triple-blind study that compares the effectiveness of the different drugs.</strong></em></p><p><em></em></p><p><em>This choice depends on the patient’s characteristics such as frequency of intercourse (occasional or regular use with 3 weekly or more intercourse), treatment expectations tolerability, and side effects.</em></p><p><em></em></p><p><em>In a recent meta-analysis, Chen et al demonstrated that patients affected by ED seeking immediate efficacy should start with Sildenafil 50 mg while others could benefit from Tadalafil 10 mg which has higher tolerability [25].</em></p><p></p><p></p><p></p><p></p><p><strong>4.1.1.5 Non-responders </strong></p><p></p><p><em><strong>Some patients do not respond adequately to oral PDE-5Is; this mainly happens for two reasons: </strong></em></p><p><em><strong></strong></em></p><p><em><strong>1. Incorrect use of the drug </strong></em></p><p><em><strong>2. Lack of actual efficacy of the prescribed molecule</strong></em></p><p><em></em></p><p><em></em></p><p><em>Regarding the incorrect use, patients must be informed about the correct intake procedure</em></p><p><em></em></p><p><em>McCullough suggests carrying out the PDE5Is treatment for at least 6/8 weeks before establishing its ineffectiveness [29]. <strong>The most frequent causes of incorrect use are as follows:</strong></em></p><p><strong></strong></p><p><strong><em>1. Failure to use an adequate dosage. </em></strong></p><p><em><strong>2. Lack of or inadequate sexual stimulation.</strong></em></p><p><em><strong></strong></em></p><p><em><strong>3. Search for intercourse ignoring the right timing of the drug. </strong>In fact, there is a period of time between the intake and the pharmacological action in which the drug will be ineffective. Moreover, some patients require a longer time for the drug to start acting [30, 31].</em></p><p><em></em></p><p><em></em></p><p><em><strong>Furthermore, the absorption of the drug can be delayed by the intake of fatty foods or a large meal.</strong></em></p><p><em><strong></strong></em></p><p><em><strong>The clinician is always required to verify that the patient has taken an official drug.<u> Unfortunately, the black market has increased over the last decades; thus, the efficacy and safety of unauthorized and uncontrolled tablets cannot be guaranteed</u>.</strong></em></p><p><em><strong></strong></em></p><p><em><strong>In addition to that, Marchal Escalona et al. recently reported that a <u>polyformism of the PDE5A gene encoding the PDE-5 enzyme may affect the efficacy of the drugs</u>. <u>Thus, there may be variability in the clinical response of the clinical response in subjects using PDE5i</u> [32].</strong></em></p><p></p><p></p><p></p><p></p><p><strong>4.1.1.6 On-Demand Vs Daily Treatment </strong></p><p></p><p><em>Recently, there has been a great interest in daily PDE5I administration as a new and innovative approach to managing erectile dysfunction. The advantage of daily intake for the management of erectile dysfunction is the complete separation of drug use from sexual activity, eliminating the unpleasant effect indicated by patients as “I feel drugs control my sex life” or “I wish they would. my erections came more spontaneously” [33]. The main goal of ED therapy is to achieve an improvement in erectile function; however, this improvement is not the only factor for sexual satisfaction. In fact, self-confidence and spontaneity of erection may play an important role in increasing the general satisfaction of patients [34]. In this regard, a study observed that patients who started ED treatment with tadalafil once a day (OaD) reported greater improvement in self-esteem and sexual spontaneity than patients who started treatment with sildenafil on-demand. On the other hand, there were no significant differences between the two regarding the improvement of IIEF-EF, orgasmic function, the domains of general satisfaction, and of the EDITS score [35].</em></p><p><em></em></p><p><em><strong>Regarding tolerability, it is <u>important to emphasize that chronic administration of tadalafil does not appear to result in up-regulation of PDE5 in human penile tissue</u>, an effect which has been observed in rat penile tissue continuously exposed to high doses of sildenafil [36, 37]. This means that the phenomenon of tachyphylaxis occurs against sildenafil and over time, the drug loses its effectiveness since more PDE5 enzymes are produced and the concentration of the drug is no longer sufficient to ensure its inhibition. <u>On the other hand, tadalafil does not seem to show a loss of its efficacy over time due to tachyphylaxis</u>. </strong>An additional benefit of tadalafil OaD is that overall drug exposure can be reduced in men who engage in sexual intercourse more than twice a week, and side effects can be minimized in men who have difficulty tolerating higher doses of PDE5I [33, 38]</em></p><p><em></em></p><p><em>The SURE multicenter study was one of the first trials to investigate the usefulness of chronic tadalafil dosing: 4262 men with ED were treated with 20 mg of tadalafil three times per week or 20 mg on-demand in a 12-day cross-over project [39]. The results of this study showed that over 60% of men in both arms of the study reported normalization of erectile function. Over 70% of men in both groups reported being able to successfully penetrate and complete intercourse. There were no differences in the success rate between routine and on-demand dosing for any efficacy parameter. There was a substantial difference in the timing of intercourse between the treatment arms: within 4 h of taking the drug, 53% of the on-demand arm attempted intercourse while only 29% of the OaD arm attempted intercourse within this time limit. This suggests greater flexibility in the OaD group. Although efficacy data showed no differences, the three-times-weekly dosing regimen for tadalafil was preferred by only 43% of enrolled patients; therefore, on-demand therapy was preferred by most men. Anyway, in the SURE study, it is evident that routine dosing may be a good option too.</em></p><p><em></em></p><p><em>The impact of daily tadalafil dosage on female partner satisfaction with sexual activity has also been a topic of recent interest and research. A partner preference study on sildenafil on-demand versus tadalafil OaD indicated that 79% of female partners preferred tadalafil OaD, citing a more relaxed approach to sexual intimacy and greater flexibility with respect to the timing of intercourse. Based on this, it can be inferred that such flexibility would be attractive to many patients’ partners [40].</em></p><p><em></em></p><p><em>However, it has to be stated that in some studies, side effects were more common at higher doses of tadalafil, but this dose-response relationship was not confirmed in all studies. In general, the incidence of these side effects decreases over time with chronic therapy [38].</em></p></blockquote><p></p>
[QUOTE="madman, post: 242300, member: 13851"] Guess those Italians who are at the top of their game when it comes to men's sexual health have no clue what the f**k they are talking about! 2022! [URL unfurl="true"]https://www.excelmale.com/forum/threads/erectile-dysfunction-medical-therapy-and-rehabilitation.26341/[/URL] [B]4.1.1.2 The Right Molecule for the Right Patient [/B] [I][B]The choice of the best PDE-5Is is not supported by any double or triple-blind study that compares the effectiveness of the different drugs.[/B] This choice depends on the patient’s characteristics such as frequency of intercourse (occasional or regular use with 3 weekly or more intercourse), treatment expectations tolerability, and side effects. In a recent meta-analysis, Chen et al demonstrated that patients affected by ED seeking immediate efficacy should start with Sildenafil 50 mg while others could benefit from Tadalafil 10 mg which has higher tolerability [25].[/I] [B]4.1.1.5 Non-responders [/B] [I][B]Some patients do not respond adequately to oral PDE-5Is; this mainly happens for two reasons: 1. Incorrect use of the drug 2. Lack of actual efficacy of the prescribed molecule[/B] Regarding the incorrect use, patients must be informed about the correct intake procedure McCullough suggests carrying out the PDE5Is treatment for at least 6/8 weeks before establishing its ineffectiveness [29]. [B]The most frequent causes of incorrect use are as follows:[/B][/I] [B] [I]1. Failure to use an adequate dosage. [/I][/B] [I][B]2. Lack of or inadequate sexual stimulation. 3. Search for intercourse ignoring the right timing of the drug. [/B]In fact, there is a period of time between the intake and the pharmacological action in which the drug will be ineffective. Moreover, some patients require a longer time for the drug to start acting [30, 31]. [B]Furthermore, the absorption of the drug can be delayed by the intake of fatty foods or a large meal. The clinician is always required to verify that the patient has taken an official drug.[U] Unfortunately, the black market has increased over the last decades; thus, the efficacy and safety of unauthorized and uncontrolled tablets cannot be guaranteed[/U]. In addition to that, Marchal Escalona et al. recently reported that a [U]polyformism of the PDE5A gene encoding the PDE-5 enzyme may affect the efficacy of the drugs[/U]. [U]Thus, there may be variability in the clinical response of the clinical response in subjects using PDE5i[/U] [32].[/B][/I] [B]4.1.1.6 On-Demand Vs Daily Treatment [/B] [I]Recently, there has been a great interest in daily PDE5I administration as a new and innovative approach to managing erectile dysfunction. The advantage of daily intake for the management of erectile dysfunction is the complete separation of drug use from sexual activity, eliminating the unpleasant effect indicated by patients as “I feel drugs control my sex life” or “I wish they would. my erections came more spontaneously” [33]. The main goal of ED therapy is to achieve an improvement in erectile function; however, this improvement is not the only factor for sexual satisfaction. In fact, self-confidence and spontaneity of erection may play an important role in increasing the general satisfaction of patients [34]. In this regard, a study observed that patients who started ED treatment with tadalafil once a day (OaD) reported greater improvement in self-esteem and sexual spontaneity than patients who started treatment with sildenafil on-demand. On the other hand, there were no significant differences between the two regarding the improvement of IIEF-EF, orgasmic function, the domains of general satisfaction, and of the EDITS score [35]. [B]Regarding tolerability, it is [U]important to emphasize that chronic administration of tadalafil does not appear to result in up-regulation of PDE5 in human penile tissue[/U], an effect which has been observed in rat penile tissue continuously exposed to high doses of sildenafil [36, 37]. This means that the phenomenon of tachyphylaxis occurs against sildenafil and over time, the drug loses its effectiveness since more PDE5 enzymes are produced and the concentration of the drug is no longer sufficient to ensure its inhibition. [U]On the other hand, tadalafil does not seem to show a loss of its efficacy over time due to tachyphylaxis[/U]. [/B]An additional benefit of tadalafil OaD is that overall drug exposure can be reduced in men who engage in sexual intercourse more than twice a week, and side effects can be minimized in men who have difficulty tolerating higher doses of PDE5I [33, 38] The SURE multicenter study was one of the first trials to investigate the usefulness of chronic tadalafil dosing: 4262 men with ED were treated with 20 mg of tadalafil three times per week or 20 mg on-demand in a 12-day cross-over project [39]. The results of this study showed that over 60% of men in both arms of the study reported normalization of erectile function. Over 70% of men in both groups reported being able to successfully penetrate and complete intercourse. There were no differences in the success rate between routine and on-demand dosing for any efficacy parameter. There was a substantial difference in the timing of intercourse between the treatment arms: within 4 h of taking the drug, 53% of the on-demand arm attempted intercourse while only 29% of the OaD arm attempted intercourse within this time limit. This suggests greater flexibility in the OaD group. Although efficacy data showed no differences, the three-times-weekly dosing regimen for tadalafil was preferred by only 43% of enrolled patients; therefore, on-demand therapy was preferred by most men. Anyway, in the SURE study, it is evident that routine dosing may be a good option too. The impact of daily tadalafil dosage on female partner satisfaction with sexual activity has also been a topic of recent interest and research. A partner preference study on sildenafil on-demand versus tadalafil OaD indicated that 79% of female partners preferred tadalafil OaD, citing a more relaxed approach to sexual intimacy and greater flexibility with respect to the timing of intercourse. Based on this, it can be inferred that such flexibility would be attractive to many patients’ partners [40]. However, it has to be stated that in some studies, side effects were more common at higher doses of tadalafil, but this dose-response relationship was not confirmed in all studies. In general, the incidence of these side effects decreases over time with chronic therapy [38].[/I] [/QUOTE]
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