Effects of Two Different Dosages of Sildenafil on Patients With Erectile Dysfunction

To investigate the effects of two different dosages of sildenafil on patients with erectile dysfunction (ED), a total of 3,674 patients with ED were recruited to answer questionnaires designed specifically for this study. There were 977 patients in the 50 mg group and there were 2,697 patients in the 100 mg group. Both 50 mg and 100 mg of sildenafil therapy increased the ED patients’ average monthly frequency of sexual intercourse, improved erectile function state in self-assessment, and elevated sexual satisfaction and enjoyment. Despite a higher rate of concomitant diseases, patients in the higher dosage of sildenafil group had a better outcome in the average monthly frequency of sexual intercourse and sexual enjoyment compared with those in the lower dosage. Such a study might be helpful for health care providers to choose sildenafil dosage for patients with ED.

Introduction

Erectile dysfunction (ED) is a common disorder and its incidence in married men is 39.1%. Incidence sharply increases as men age (Corona, Rastrelli, Maseroli, Forti, & Maggi, 2013). ED is defined as the inability to attain and/or maintain penile erection sufficient for satisfactory sexual intercourse. The etiology and pathogenesis for ED are not yet fully understood. However, the following factors may play a role: endothelial impairment, low testosterone levels, prior surgical manipulation, and/or psychogenic components (Patel, Halls, & Patel, 2012). From a clinical standpoint, occasional erectile trouble is not necessarily a cause for concern. If ED is an ongoing problem, it may understandably cause stress, affect one’s self-confidence, and exacerbate relationship problems between partners. In fact, penile erection is a very complicated process requiring neurally mediated relaxation of arteriolar smooth muscle and the engorgement of cavernosal tissues. Nitric oxide plays a critical role in the process and prevailing therapies for ED typically focus on maximizing endogenous nitric oxide signaling (Masuda, 2008). Sildenafil is a highly selective and extensively used phosphodiesterase type 5 inhibitor (PDE-5) which elicits a firm therapeutic effect (Goldstein et al., 1998). ED treatment primarily aims to help patients achieve satisfactory sexual lives. The common dose is 100 mg or 50 mg. There is no consensus as to whether the selective mode and therapeutic effect of the two sildenafil doses differ. In the current study, ED patients from numerous centers in China who used 100 mg and 50 mg sildenafil therapy were retrospectively analyzed to investigate the effect of variable sildenafil dosage.

Subjects and Method

General Clinical Samples

Patients with ED from 47 hospitals participated in the current study. From May 2008 to May 2009, 3,674 patients came to the Andrology Clinics for ED and were administered the PDE-5 inhibitor sildenafil according to their sexual life demands and followed up closely. Patients’ general health statuses including medical histories (hypertension, diabetes, coronary heart disease, hyperlipemia, and others) and erectile function self-assessments as well as the reported therapeutic effects were reviewed. Specialists screened the newly diagnosed ED patients first and then helped them finish the correlative questionnaires (International Index of Erectile Function: IIEF-5 and IIEF Q1-IIEF Q6) based on the answers from the patients. All patients were then selected to two different dosage group (50 mg vs. 100 mg of sildenafil) mainly based on patients’ preference unless there was a contraindication. After the treatment of PDE-5 inhibitor for 8 weeks, the returning patients completed the therapeutic effect questionnaires and data were analyzed. Patients who were recruited for the 50 mg dosage group would continue use the same dosage for 8 weeks until this study ended. If patients complained of insufficient response, 100 mg would be given to these patients afterward.

Age distribution
Years of course

The years of the ED course were grouped according to 10 years, and the percentage of each group in the 50 mg group was 77.3%, 19.0%, and 3.7%. The percentage of each in the 100 mg group was 73.6%, 20.7%, and 5.8%, and the difference between the two groups was statistically significant (p < .05). The percentage of patients with a shorter ED course in the 50 mg group was higher than that in the 100 mg group, while the percentage of patients with a longer ED course was lower than that in the 100 mg group.

Life style

The percentage of smokers in the 50 mg group was 60.0%, while it was 61.3% in the 100 mg group; this difference in the percentage of smokers between these two groups was not statistically significant (p > .05). The percentage of alcohol drinkers in the 50 mg group was 58.0%, while it was 59.4% in the 100 mg group. The difference in percentage of drinkers was not statistically significant (p > .05).

Concomitant diseases

Patients with no concomitant disease in the two groups constituted 64.8% of participants, whereas 35.2% of the patients had concomitant disease. The percentage of patients combined with the 1 to 4 disease was 28.1%, 5.9%, 0.9%, and 0.4%, respectively. In the 50 mg group, 29.7% of the patients had concomitant disease, which was lower than the 100 mg group (37.2%). The difference in percentage of concomitant diseases between these two groups was statistically significant (p < .01).

Therapeutic Effect Index

All ED patients completed sildenafil therapy for 8 weeks, and data were collected as to: self-assessment improvements regarding erectile function, ED severity after treatment, sexual satisfaction, average monthly frequency of sexual intercourse, and sexual enjoyment. Patients completed the IIEF-5 and IIEF Q1 to IIEF Q6 before and after treatment. All data from the two groups after treatment were calculated and analyzed statistically. The standard of the IIEF can be divided into: normal ≥21, mild 17 to 20, moderate 11 to 16, and severe 6 to 10.

Statistical Analysis

All statistical analyses were conducted using SPSS vs.13.0, t test, and correlative statistical analyses. χ 2 analysis was used for ratios/percentage, and p < .05 was considered statistically significant.

Results

Average Monthly Frequency of Sexual Intercourse

The change on sexual frequency after sildenafil treatment.

Improvement of Erectile Function in Self-Assessment

Sexual Satisfaction

Both the 50 mg group and the 100 mg group improved sexual satisfaction following sildenafil treatment. In the 50 mg group prior to treatment, the ratio of severely unsatisfactory, moderately unsatisfactory, and mildly unsatisfactory sexual satisfaction was 20.4%, 50.9%, and 27.5%, respectively. In the 100 mg group, this ratio was 28.7%, 47.2%, and 22.4%, respectively. The sexual satisfaction of the 100 mg group was significantly lower than the 50 mg group, and the difference between the two groups was considered statistically significant (p < .01). The ratios of sexual satisfaction that were moderately unsatisfactory, mildly satisfactory, moderately satisfactory, and very satisfactory were 5.0%, 20.9%, 58.1%, and 15.3%, respectively, in the 50 mg group after therapy. In the 100 mg group, these ratios were 4.0%, 22.5%, 59.3%, and 13.1%, respectively. The difference between the two groups was not considered statistically significant (p > .05; Figure 2 ).

The change on sexual life satisfactory degree after sildenafil treatment.

Sexual Enjoyment

Both the 50 mg group and the 100 mg group significantly improved sexual enjoyment following sildenafil treatment. In the 50 mg group prior to treatment, the ratios of sexual enjoyment as to nothing, absolutely enjoy, moderately enjoy, and mild enjoy were 5.0%, 26.0%, 43.1%, and 25.6%, respectively. In the 100 mg group, they were 9.3%, 29.4%, 39.3%, and 21.1%, respectively. The difference between the two groups was not considered statistically significant (p < .01). The ratios of sexual enjoyment that were nothing, absolutely unenjoy, moderately unenjoy, mild unenjoy, very enjoy, and extremely enjoy were 0.1%, 1.3%, 8.6%, 37.2%, 49.2%, and 3.6%, respectively, in the 50 mg group after treatment, while they were 0.0%, 1.7%, 5.6%, 41.3%, 47.5%, and 3.8% in the 100 mg group, respectively. The sexual enjoyment of the 100 mg group was significantly higher than the 50 mg group, and the difference between the two groups was considered statistically significant (p < .01; Figure 3 ).

The change on sexual enjoyment after sildenafil treatment.

The Influence of Concomitant Disease on Dose Selection

There were 2,381 patients, or 64.8% of the 3,674 patients, with no concomitant disease who completed the sildenafil 50 mg and 100 mg treatment. There were 1,293 patients with concomitant disease constituting 35.2% of all patients, and among them the ratios of the No. 1 to No. 4 concomitant disease were 28.1%, 5.9%, 0.9%, and 0.4%, respectively. In the 50 mg group, 70.3% had concomitant disease, while 29.7% did not. In the 100 mg group, 62.8% had concomitant disease, whereas 37.2% did not. The difference between the two groups was considered statistically significant (p < .01), and the ratio of patients with concomitant disease was significantly higher in the 100 mg group than in the 50 mg group. The difference between before and after treatment for patients with and without concomitant disease was statistically significant in the IIEF, IIEF Q1 to IIEF Q6 (p < .01). These scores increased sharply after treatment compared with before, and 96.8% and 93.5% of the 50 mg group asserted erectile function in the self-assessment improvement, whereas 96.5% and 96.1% said the same in the 100 mg group.

The 50 mg Sildenafil Group

The ratios of ED severity (IIEF-5) that were normal, mild, moderate, and severe were 45.2%, 48.5%, 5.7%, and 0.6%, respectively, in patients with no concomitant disease after treatment. On the other hand, these ratios were 34.4%, 52.2%, 8.9%, and 4.5%, respectively, in patients with concomitant disease. The difference in ED severity between patients with concomitant disease and without concomitant disease after the treatment was statistically significant (p < .01).

The 100 mg Sildenafil Group

The ratios of ED severity (IIEF-5) that were normal, mild, moderate, and severe were 43.0%, 48.8%, 7.1%, and 1.2%, respectively, in patients with no concomitant disease after therapy. However, these ratios were 32.1%, 57.3%, 8.8%, and 1.8%, respectively, in patients with concomitant disease. The ED severity of patients without concomitant disease was significantly lower than patients with concomitant disease, and the difference between the two groups was statistically significant (p < .01).

Discussion

The current study reported that both 50 mg and 100 mg of sildenafil therapy increased ED patients’ average monthly frequency of sexual intercourse, improved erectile function in self-assessment, elevated sexual satisfaction, and improved enjoyment. Higher dosage of sildenafil had a better outcome in the average monthly frequency of sexual intercourse and sexual enjoyment. The current study is particularly interesting and noteworthy as it involves the recruitment of almost 4,000 patients from multiple clinics in China.

ED is a common and frequently encountered disease among older men. The epidemiological survey in the community illustrates that the incidence of ED in married men is 39.1%, and that incidence itself notably increases as men age (Corona et al., 2013). PDE-5 inhibitor sildenafil is an admittedly common, safe, effective, and frequently used medication which improves men’s erectile function (Akand et al., 2015; Bai et al., 2015). A broad meta-analysis ascertains that the effective power of sildenafil to improve erectile function is 3.57 times that of placebo (Tsertsvadze et al., 2009); 50 mg and 100 mg sildenafil therapy are typically used. However, there is no unified standard of dose selection for oral demand as to ED treatment, and there is not as of yet a standard as to dose selection and therapeutic effects for different ED patients both in China and abroad.

This study was performed by retrospective analysis of 3,674 ED patients. Overall, average monthly frequency of sexual intercourse, erectile function in self-assessment, sexual satisfaction, and enjoyment all improved significantly after the 50 mg or 100 mg sildenafil treatment. There were significant differences in IIEF and IIEF Q1 to IIEF Q6 between pretreatment and posttreatment. The sexual enjoyment in the 100 mg group was higher than the 50 mg group after the treatment, but between groups there were no significant differences in average monthly frequency of sexual intercourse, erectile function in self-assessment improvement, and sexual satisfaction. Thus, ED patients with lower average monthly frequency of sexual intercourse, lower sexual satisfaction, and decreased enjoyment with concomitant disease are candidates for 100 mg sildenafil.

Theoretically, high dose predicts a better therapeutic effect. There is a direct correlation between the dose of sildenafil and its therapeutic effect. Animal experiments have confirmed that different concentrations of cGMP in vivo could result in different extension degrees in corpus cavernosum penis smooth muscle in bandicoots (Akand et al., 2015; da Silva et al., 2013). Furthermore, they indicated that administration of different doses of PDE-5 inhibitors could generate different extension degrees in corpus cavernosum penis smooth muscle and generally resulted in different improvements of erectile function. As the diagnosis of ED and the evaluation of the therapeutic effect are prone to be influenced by subjective factors, different doses can result in artifacts of the placebo. It has been reported that the effects of different doses of sildenafil for erectile function improve the patients’ self-confidence against anxiety and the fear of sexual intercourse (Kirby, Creanga, & Stecher, 2013; Olsson et al., 2000). However, there is no significant improvement in the objective indices.

There was no significant difference between the 100 mg group and the 50 mg group in average monthly frequency of sexual intercourse, erectile function in self-assessment, and sexual satisfaction. It is speculated that this might be because the two groups of patients had different ED severity; the former were more serious than the latter in sexual satisfaction, average monthly frequency of sexual intercourse, and sexual enjoyment prior the treatment. Once again, this difference was considered statistically significant, and the indices of the former were significantly lower than the latter. Moreover, the ratio of patients with concomitant disease in the 100 mg group (37.2%) was significantly higher than the 50 mg group (29.7%). For this reason, doctors often give higher doses of sildenafil to the 100 mg group to achieve the same therapeutic effect (Mulhall, Creanga, & Stecher, 2013). The differences in all indices (erectile function in self-assessment, ED severity, and sexual satisfaction) between the two groups were not considered statistically significant after treatment for 8 weeks. The average monthly frequency of sexual intercourse and the sexual enjoyment of the 100 mg group were significantly higher than the 50 mg group. Besides being more effective at improving the erectile function pharmaceutically, 100 mg sildenafil can significantly improve the patients’ self-confidence, eliminate the fear of sexual intercourse, and is better at improving the patients’ self-confidence and subjective opinions. Thus, despite of the differences in age, ED disease course and concomitant diseases between 50 mg and 100 mg sildenafil group, 100 mg of sildenafil seems a more effective therapy dose for ED treatment. In the current study, if patients who were recruited in 50 mg dosage group were not satisfied with the outcome evaluated at the end of this study (the end of Week 8), 100 mg would be given to these patients afterward.

Patients with cardiovascular disease, diabetes, and hyperlipidemia are of particular interest. Along with patients who have long been administered pimobendane or hypoglycemic, hypolipidemic, and hypotensive agents, all aforementioned conditions carry a significantly higher ED incidence than normal (Gareri, Castagna, Francomano, Cerminara, & De Fazio, 2014; Malavige & Levy, 2009; Nascimento et al., 2013). It is suggested that there is close correlation between ED invasion, ED severity, and concomitant disease. Thus, the current research statistically analyzed the therapeutic effect of PDE-5 inhibitors in patients with and without concomitant disease, respectively. The sexual satisfaction, average monthly frequency of sexual intercourse, and sexual enjoyment indices of patients without concomitant disease was significantly higher than patients with concomitant disease in the 50 mg group before treatment. There was still a statistical difference in these three indices and a significant difference in erectile function in self-assessment and ED severity after treatment, but patients with no concomitant disease fared significantly better than patients with concomitant disease. Similar to the reviewed 50 mg group, there were significant differences in sexual satisfaction, average monthly frequency of sexual intercourse and sexual enjoyment between patients with concomitant disease and without concomitant disease in the 100 mg group before treatment. Moreover, there was still a significant difference after treatment. The ED severity in patients without concomitant disease was significantly more improved than patients with concomitant disease after treatment. However, there was no significant difference in the improvement of erectile function in self-assessment between pretreatment and posttreatment in the two groups. It is concluded that both 50 mg and 100 mg sildenafil improve patients’ erectile function, even with and without concomitant disease. In these two groups, there was significant improvement in sexual satisfaction, average monthly frequency of sexual intercourse, and sexual enjoyment, irrespective of the dose of sildenafil. Furthermore, there was no significant correlation between increasing dose and improvement. It is considered that with increasing sildenafil dose, one can better improve the patients’ self-confidence as to erectile function. And, with other concomitant diseases, one can decrease the fear of failure in a patient’s sexual life, thus improving their erectile function indirectly.

In summary, sildenafil therapy increased the ED patients’ average monthly frequency of sexual intercourse, improved the erectile function state in self-assessment, elevated sexual satisfaction, and improved enjoyment. Higher dosage of sildenafil had a better outcome in the average monthly frequency of sexual intercourse and sexual enjoyment. The current study may prove useful for health care providers to manage patients with ED seeking improved sexual satisfaction and self-confidence.

Footnotes

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.