Efficacy and safety of phosphodiesterase type 5 inhibitors on primary premature ejaculation in men receiving selective serotonin reuptake inhibitors therapy: a systematic review and meta‐analysis

We performed a systematic review and meta‐analysis to assess whether selective serotonin reuptake inhibitors (SSRIs) and phosphodiesterase type 5 inhibitors ( PDE5‐Is ) may have an additive therapeutic effect. A literature review was performed to identify all published randomised controlled trials (RCT) that used SSRIs combined with PDE5‐Is therapy for the treatment of primary PE. The search included the following databases: EMBASE, MEDLINE and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. Five publications involving a total of 419 patients were used in the analysis, including 5 RCTs that compared PDE5‐Is plus SSRIs with SSRIs treating primary PE. Primary efficacy endpoints: IELT (the standardised mean difference (SMD) = 1.07, 95% confidence interval (CI) = 1.00 to 1.14, P < 0.00001) indicated that utilisation of PDE5‐Is and SSRIs was more effective than the SSRIs alone for a long time in patients with primary PE. Safety assessments included headache (odds ratio (OR) = 3.16, 95% CI = 1.63 to 6.11, P = 0.0006), and flushing indicated that PDE5‐Is plus SSRIs were well tolerated. This meta‐analysis indicates that PDE5‐Is combined with SSRIs seem to provide significantly better ejaculatory latency time as compared with SSRIs alone in patients with primary PE.     

Efficacy of phosphodiesterase type 5 inhibitors in patients with erectile dysfunction after nerve-sparing radical prostatectomy: a systematic review and meta-analysis

BackgroundNerve-sparing radical prostatectomy (NSRP) had to be performed because approximately 94% of patients are diagnosed with localized prostate cancer (PCa). Although NSRP is generally done to improve functional outcomes, erectile dysfunction (ED) is one of the most prevailing complications after radical prostatectomy (RP). Phosphodiesterase type 5 inhibitors (PDE5-Is) are the most well-known treatment agent for postoperative ED. This study aimed to assess the efficacy of PDE5-Is in patients with ED after NSRP.MethodsIn this systematic literature review, randomized controlled trials on the efficacy and safety of PDE5-Is in patients who underwent NSRP were searched in MEDLINE, EMBASE, and the Cochrane Controlled Trials Register using the OVID platform. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane Review Methods. The quality of the evidence of the outcome data was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.ResultsA total of 14 trials involving 2,822 patients were included. Significant improvements in the International Index of Erectile Function—Erectile Function (IIEF) domain score [mean difference (MD) =4.93; 95% confidence interval (CI): 4.14–5.71; P<0.00001] and erectile function recovery events [odds ratio (OR) =2.06; 95% CI: 1.45–2.94; P<0.0001] were observed after PDE5-I treatment. A higher positive response to Sexual Encounter Profile (SEP) question 2 (OR =2.27; 95% CI: 1.80–2.86; P<0.00001) and question 3 (OR =2.78; 95% CI: 1.97–3.91; P<0.00001) was also found after PDE5-I treatment. However, the incidence of treatment-emergent adverse events (TEAEs) was higher after PDE5-I treatment than after placebo treatment (OR =2.91; 95% CI: 1.84–4.61). Furthermore, the incidence of headache (OR =3.38; 95% CI: 2.40–4.75) and flushing (OR =9.44; 95% CI: 4.30–20.70) was also significantly higher after PDE5-I treatment (P<0.00001). In terms of the quality of the evidence of the outcome data, inconsistency problems were detected in all outcomes and imprecision problems in most outcomes.DiscussionPDE5-I treatment was more effective to placebo treatment in patients with ED after NSRP. No clinically serious complications were found in spite of the incidence of TEAEs being higher after PDE5-I treatment.     

Comparison of efficacy and safety of daily oral L-arginine and PDE5Is alone or combination in treating erectile dysfunction: A systematic review and meta-analysis of randomised controlled trials

The meta-analysis was performed to assess the efficacy and safety of daily oral L-arginine and phosphodiesterase type 5 inhibitors (PDE5Is) alone or combination in treating patients with erectile dysfunction (ED). We performed a search of randomised controlled trials in the following databases: PubMed, EMBASE and Cochrane Library databases. Four articles including 373 patients were studied. Erectile functions were significantly improved in three therapy groups compared with baseline. Patients who received the combination of L-arginine and PDE5Is showed significant improvement compared to those treated with L-arginine and PDE5Is alone, as assessed by sexual function index (p <0.00001 and p =0.005, respectively) and total testosterone (p <0.00001 and p =0.0007, respectively). Furthermore, patients who treated with PDE5Is alone exhibited the better efficacy than those treated with L-arginine alone in respects of sexual function index (p <0.00001) and total testosterone (p =0.0001). However, the combination of L-arginine and PDE5Is had no obvious difference relative to PDE5Is alone in terms of various adverse events (AEs). Conclusively, compared with monotherapy, the combination of L-arginine and PDE5Is showed a greater improvement of sexual function and total testosterone, and did not significantly increase the AEs. Besides, PDE5Is alone revealed a better effect than those treated with L-arginine alone for patients with ED.     

Platelet Cyclic Guanosine Monophosphate as a Biomarker of Phosphodiesterase Type 5 Inhibitor Efficacy in the Treatment of Erectile Dysfunction: A Randomized Placebo-Controlled Study

Background

Phosphodiesterase 5 inhibitors (PDE5-Is) are a mainstay in the therapy of erectile dysfunction (ED). The primary end point of clinical efficacy, both in clinical studies and normal practice, is represented by the International Index of Erectile Function (IIEF).

Objective

To evaluate if platelet cyclic guanosine monophosphate (cGMP) could represent a valuable marker for PDE5-I activity in ED.

Design, setting, and participants

The study enrolled 46 patients with psychogenic, organic, and mixed ED (20–71 yr of age; IIEF score <26). Patients were randomized to 6 wk of vardenafil, 5 mg/d at bedtime, or placebo.

Intervention

All patients donated two blood samples, one before starting the protocol and the second after 6 wk of treatment.

Measurements

Platelet cGMP was measured in both placebo and vardenafil groups. All the patients completed the IIEF-Erectile Function (EF) domain and the sexual encounter profile (SEP) and underwent visual sexual stimulation (VSS) coupled with Rigiscan. All the measurements were performed prior to starting the protocol and after the 6 wk of treatment.

Results and limitations

Platelet cGMP production was significantly (p < 0.05) elevated in patients taking 5 mg vardenafil versus placebo. Vardenafil was not superior to placebo in improving IIEF-EF and SEP scores. Conversely, VSS-Rigiscan revealed a significant amelioration (p < 0.028) in the vardenafil group versus placebo. The changes in platelet cGMP level correlated well with VSS-Rigiscan (p = 0.0037) but not with IIEF-EF and SEP.

Conclusions

Platelet cGMP could represent a relatively simple, reliable, and objective biomarker of PDE5-I activity in ED clinical studies. Larger clinical studies are needed to further validate the use, utility, and limits of this assay.     

Serum vitamin D levels and erectile dysfunction: A systematic review and meta‐analysis

Suboptimal levels of serum vitamin D levels have been implied to be associated with cardiovascular diseases and endothelial dysfunction, conditions closely associated with erectile dysfunction (ED). The present systematic review and meta‐analysis was performed to evaluate the vitamin D levels in subjects with ED compared to controls and the 5‐item version of the international index of erectile function (IIEF‐5) score in subjects with vitamin D deficiency compared to those without vitamin D deficiency in order to elucidate the role of vitamin D in the pathogenesis of ED. Studies evaluating the possible association between vitamin D levels and ED were initially screened and thus included following electronic literature search of database Cochrane Library, PUBMED, EMBASE and MEDLINE. Essential article information including outcome measures was extracted from the qualified studies by two independent authors, and STATA 12.0 software was used conducted the meta‐analysis. Subgroup analyses were conducted by vitamin D detection methods and sample size. The standard mean difference (SMD) as well as the 95% confidence intervals (95% CIs) was applied to estimate the outcome measures. A total of seven articles were included in our meta‐analysis with a total of 4,132 subjects. Pooled estimate was in favour of increased vitamin D levels in subjects without ED with a SMD of 3.027 ng/ml, 95%CI 2.290–3.314, p = 0.000. However, subgroup analysis showed an opposite trend, after one study with a sample size over 1,000 that could possibly influence the weight balance was excluded, with a SMD of 0.267, 95%CI ?0.052 to 0.585, p = 0.101. We also identified about 0.320 higher in IIEF‐5 score (95%CI = 0.146–0.494, p = 0.000) in subjects without vitamin D deficiency versus with vitamin D deficiency. Nevertheless, subgroup analysis based on vitamin D detection methods obtained differential results (radioimmunoassay subgroup, SMD(95%CI) = 0.573 (0.275–0.870), p = 0.000; immunoassay subgroup, SMD(95%CI) = 0.189 (?0.025 to 0.404), p = 0.084). In conclusion, results from the present meta‐analysis did not provide a strong relationship between vitamin D and the risk of ED. However, the results should be interpreted with caution and more high quality studies are warranted.     

Evaluation of the efficacy and safety of once-a-day dosing of tadalafil 5mg and 10mg in the treatment of erectile dysfunction: results of a multicenter, randomized, double-blind, placebo-controlled trial

BACKGROUND: Erectile dysfunction (ED) is a chronic disease; however, therapy is currently administered as needed with oral phosphodiesterase 5 (PDE5) inhibitors like tadalafil. Because the 17.5-h half-life of tadalafil enables therapeutic plasma levels to be sustained with daily administration, tadalafil is a good candidate for once daily dosing therapy. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group, 12-week study enrolled 268 men 1:2:2 to placebo, tadalafil 5mg, and tadalafil 10mg taken once daily. Primary efficacy measures included changes in the International Index of Erectile Function Erectile Function domain (IIEF EF), Sexual Encounter Profile diary Questions 2 (SEP2: successful penetration), and 3 (SEP3: successful completion of intercourse), and tolerability. Secondary measures included percentage of patients at endpoint who reported improved erectile function (EF), and percentage who reported "no ED" (IIEF EF score 26-30). RESULTS: For patients who took placebo, tadalafil 5mg, and tadalafil 10mg, changes from baseline to endpoint were, respectively, 0.9, 9.7, and 9.4 for IIEF EF; 11.2, 36.5, and 39.4 for SEP2; and 13.2, 45.5, and 50.1 for SEP3. At endpoint, 28.3%, 84.5%, and 84.6% reported improved erections, and 8.3%, 51.5%, and 50.5% reported "no ED," respectively. All comparisons between tadalafil and placebo were significant (p<0.001). Adverse events that occurred in at least 5% of patients were dyspepsia, headache, back pain, upper abdominal pain, and myalgia; nine patients (3.4%) discontinued because of adverse events. CONCLUSIONS: Once-a-day tadalafil 5mg or 10mg was well tolerated and significantly improved EF in men with ED.     

Elevated serum homocysteine level as an independent risk factor for erectile dysfunction: a prospective pilot case–control study

Homocysteine is an amino acid that is produced from the metabolic demethylation of dietary methionine. It has gained arising attention for its association with increased risk of myocardial infarction, stroke and venous thromboembolism. Erectile dysfunction (ED), especially for vasculogenic ED, is a vascular disorder of cavernosal vascular bed. In this prospective pilot case–control study, we investigated plasma homocysteine levels in 32 ED patients and 20 healthy control men. Related patients characteristics including age, weight, height, marital status, smoking and drinking status, level of education were collected and analysed as well as penile colour Doppler ultrasound parameters. ED patients were further categorised into mild, moderate and severe ED based on 5‐item of the International Index of Erectile Function. Higher homocysteine levels were observed in ED patients as compared with controls (p < .05). A multivariate logistic regression with likelihood ratio test revealed that homocysteine and penile peak systolic blood flow velocity (PSV) levels posed significant indicators for ED (chi‐square of likelihood ratio = 20.42, df = 2, p < .005) as well as moderate and severe ED occurrence (chi‐square of likelihood ratio = 28.50, df = 2, p < .005). The threshold value of homocysteine concentration to discriminate ED and control subjects was 12.65 μmol/L by performing receiver operating characteristic curve analyses. These data suggested that elevation of homocysteine levels was associated with an increased risk of ED.     

The effect of using tadalafil 5 mg/day on neutrophil–lymphocyte and platelet–lymphocyte ratios in mild‐medium and severe erectile dysfunction patients; and comparison of clinical response

To examine the relation between NLR (neutrophil–lymphocyte ratio) and PLR (platelet–lymphocyte ratio) rates and the severity of ED (erectile dysfunction) and the effect of tadalafil 5 mg/day on these, a total of 143 patients were retrospectively evaluated. Sixty‐three patients with ED who came for follow‐up examinations in the 1st month of the treatment were included as the study group, and 80 men who were not diagnosed with ED were as the control group. The age and Charlson Comorbidity Indexes (CCI) of the study and control groups were compared with the IIEF 5, NLR and PLR values before and after the treatment. The mean age and median CCI were higher in the severe ED group (p < 0.05). The mean NLR and PLR values were lower in the control group (p < 0.001). In the study group, the NLR and PLR values decreased with the increase in the IIEF 5 scores (p < 0.001). The ROC curve was significant for the NLR and PLR scores (AUC = 0.779, [95% CI: 0.698–0.860]; AUC = 0.754, [95% CI: 0.670–0.838] p < 0.001). Although more prospective and randomized studies are needed, the systemic inflammation decreases and the clinical symptoms improve in patients who use tadalafil 5 mg/day.     

Associations between erectile dysfunction and psychological disorders (depression and anxiety): A cross‐sectional study in a Chinese population

The present cross‐sectional survey was performed to evaluate the prevalences and correlations of depression and anxiety among Chinese erectile dysfunction (ED) men. Between February 2017 and January 2019, male patients with or without ED treated in andrology clinic and urology clinic were enrolled in the investigation. All enrolled patients were required to fill in the International Index of Erectile Function Questionnaire (IIEF‐5), Patient Health Questionnaire (PHQ‐9) and Generalized Anxiety Disorder 7‐item scale (GAD‐7) which intended to evaluate the diagnosis and severity of ED, depression and anxiety respectively. Of the 958 included participants, 79.82% (613/768) and 79.56% (611/768) ED patients appeared to have anxiety and depression; 13.68% (26/190) of men without ED had anxiety and depression. In addition, young ED patients (age ≤35 years) and long ED duration patients (duration >12 months) had higher incidences and severities of anxiety and depression (p < .05). After adjusting the age, IIEF‐5 was negatively correlated with PHQ‐9 (adjusted r = ?.653, p < .001) and GAD‐7 scores (adjusted r = ?.607, p < .001). The prevalences of anxiety and depression were 79.82% and 79.56% in Chinese ED patients. The prevalences and severities of anxiety and depression increased as the ED severity increased. Based on the high incidences of anxiety and depression among Chinese ED patients, clinicians are supposed to pay more attention to early diagnosis and therapy of psychiatric symptoms for ED patients, especially among young patients and patients with long ED duration.     

Efficacy and safety of long‐term tadalafil 5 mg once daily combined with sildenafil 50 mg as needed at the early stage of treatment for patients with erectile dysfunction

This study aimed to evaluate the efficacy and safety of long‐term and low‐dose tadalafil combined with sildenafil as needed at the early stage of treatment for erectile dysfunction (ED). We enrolled 180 patients with ED 1 : 1 to tadalafil 5 mg once daily or once‐a‐day tadalafil 5 mg combined with sildenafil 50 mg as needed. The efficacy measures included the 5‐item version of the International Index of Erectile Function (IIEF‐5) and the Sexual Encounter Profile (SEP). The safety was assessed by observing drug tolerability and adverse events. Total IIEF‐5 scores of patients with severe ED in combined medication group were significantly higher than in tadalafil alone group. Question 2 scores of IIEF‐5 of patients with moderate and severe ED in combined medication group were significantly higher than in tadalafil alone group. The significant improvement in question 3 scores of IIEF‐5 existed only in patients with severe ED receiving combined medication. The percentage of ‘yes’ responses to SEP4, SEP5 and partner's SEP3 were improved significantly in combined medication group. There was no difference between two groups in the incidence of adverse events. Our results suggest that combined medication can better improve erectile function, especially for patients with severe ED.     

A meta-regression evaluating the effectiveness and prognostic factors of oral phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction

The effectiveness of phosphodiesterase type 5 inhibitors (PDE5-Is) for erectile dysfunction (ED) varies considerably among trials, but available studies investigating the factors that affect the effectiveness are few and findings are not consistent. A systematic search was performed in PubMed, Cochrane Library, and EMBASE to identify randomized controlled trials comparing PDE5-Is with placebo for the treatment of ED. The methodological quality of included studies was assessed by the Cochrane Collaboration''s tool for assessing risk of bias. The associations between prespecified study-level factors and effectiveness were tested by a random effects meta-regression model. This study included 93 trials with 26 139 patients. When all PDE5-Is were grouped together, Caucasian ethnicity was associated with 15.636% (95% confidence interval [CI]: 0.858% to 32.579%) increase in risk ratio (RR) for Global Assessment Questionnaire question-1 (GAQ-1), and 1.473 (95% CI: 0.406 to 2.338) score increase in mean difference (MD) for posttreatment International Index of Erectile Function-Erectile Function domain score (IIEF-EF), compared to Asian ethnicity. A one-score increase in baseline IIEF-EF was associated with −5.635% (95% CI: −9.120% to −2.017%) reduction in RR for GAQ-1, and −0.229 (95% CI: −0.425 to −0.042) score decrease in MD for posttreatment IIEF-EF. In conclusion, PDE5-Is are more effective in Caucasians than Asians, and in patients with more severe ED.     

Subjective effects of Lepidium meyenii (Maca) extract on well‐being and sexual performances in patients with mild erectile dysfunction: a randomised,double‐blind clinical trial

Lepidium meyenii (Maca) is a cultivated root belonging to the brassica family used in the Andean region for its supposed aphrodisiac properties. We carried out a double‐blind clinical trial on 50 Caucasian men affected by mild erectile dysfunction (ED), randomised to treatment with Maca dry extract, 2400 mg, or placebo. The treatment effect on ED and subjective well‐being was tested administrating before and after 12 weeks the International Index of Erectile Function (IIEF‐5) and the Satisfaction Profile (SAT‐P). After 12 weeks of treatment, both Maca‐ and placebo‐treated patients experienced a significant increase in IIEF‐5 score (P < 0.05 for both). However, patients taking Maca experienced a more significant increase than those taking placebo (1.6 ± 1.1 versus 0.5 ± 0.6, P < 0.001). Both Maca‐ and placebo‐treated subjects experienced a significant improvement in psychological performance‐related SAT‐P score, but the Maca group higher than that of placebo group (+9 ± 6 versus +6 ± 5, P < 0.05). However, only Maca‐treated patients experienced a significant improvement in physical and social performance‐related SAT‐P score compared with the baseline (+7 ± 6 and +7 ± 6, both P < 0.05). In conclusion, our data support a small but significant effect of Maca supplementation on subjective perception of general and sexual well‐being in adult patients with mild ED.     

Hypertension might be a risk factor for erectile dysfunction: a meta‐analysis

The study aimed to evaluate whether hypertension was a risk factor for erectile dysfunction (ED). Databases including PubMed and Embase were retrieved to identify studies related to hypertension in ED patients. Odds ratio (OR) and 95% confidence interval (CI) were used as the effect size. Subgroup analyses stratified by total number of enrolled subjects and research regions were performed. Sensitivity analysis was performed by removing a single study at one time. Egger's test was used to evaluate the publication bias. Totally, 40 studies including 121,641 subjects were included in the meta‐analysis. As a result, hypertension was closely related to ED (OR = 1.74, 95% CI, 0.63–0.80, p < .01). Subgroup analysis indicated hypertension was the risk factor for ED whatever the participants numbers. When stratified by different regions, hypertension was a risk factor for ED in Africa (OR = 3.35, 95% CI, 1.45–7.77, p < .01), Americas (OR = 1.97, 95% CI, 1.68–2.31, p < 0.01), Asia (OR = 1.46, 95% CI, 1.16–1.84, p < .01) and Europe (OR = 1.83, 95% CI, 1.34–2.49, p < .01), but not in Australia. Hypertension may be a potential risk factor for ED.     

Early intervention with phosphodiesterase‐5 inhibitors after prostate brachytherapy improves subsequent erectile function

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To examine the early use of phosphodiesterase‐5 inhibitor (PDE‐5i; sildenafil citrate) in preventing subsequent erectile dysfunction (ED) after (monotherapy) prostate brachytherapy (PB, an accepted option for Gleason 6 or low‐volume Gleason 7 prostate cancer), as PB is currently being offered more frequently in younger patients, and ED can be a side‐effect often within the first 12 months after treatment.

PATIENTS AND METHODS

We examined a single‐surgeon series of 69 patients who had been treated with PB from 2002 to 2005. All patients had a follow‐up of ≥1 year; prospectively, and patients had baseline, 6‐ and 12‐month assessments using the Sexual Health Inventory for Men (SHIM) and International Index of Erectile Function (IIEF)‐6 scores. The 69 patients were divided into early treatment with PDE‐5i (31) and not treated with PDE‐5i (38), and their SHIM and IIEF‐6 scores were compared at baseline, 6 and 12 months. Daily sildenafil (25–50 mg) was given immediately after PB for 12 months. Overall, for the entire group, the mean prostate‐specific antigen (PSA) level was 6.8 ng/mL; 78% had Gleason 6 cancer and 20% had Gleason 7 (3 + 4) cancer. The mean age in the early PDE‐5i group was 64.8 years, and was 66.0 years in the no‐PDE‐5i group. The mean radiation dose in the early PDE‐5i group was 50.2 Gy, and 43.9 Gy in the other group (P= 0.08).

RESULTS

In the no‐PDE‐5i group, the mean baseline SHIM score of 17.1 decreased rapidly to 9.1 at 6 months (P= 0.01) and stayed at 9.3 at 12 months (P= 0.01). In the early PDE‐5i group, the mean baseline SHIM score of 21.8 decreased slightly to 17.6 at 6 months (P= 0.2), and was maintained at 17.9 at 12 months (P= 0.2). Using the Wilcoxon rank‐sum test, the 6‐ and 12‐month SHIM scores in the two groups (P < 0.001). The IIEF‐6 questionnaire confirmed the SHIM analysis.

CONCLUSIONS

After PB patients had a significant decline in SHIM/IIEF‐6 scores at 6 and 12 months. Our results indicate a 50% decrease in the quality of their erections. This provides an opportunity to initiate early intervention with PDE‐5i or perhaps vacuum constriction devices or intraurethral alprostadil. In this study, the early use of PDE‐5i after PB maintained erectile function at both 6 and 12 months.     

Comparative Effectiveness and Safety of Oral Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction: A Systematic Review and Network Meta-analysis

Context

Phosphodiesterase type 5 inhibitors (PDE5-Is) are currently the first-line therapy for erectile dysfunction (ED), but available studies investigating the comparative effects of different PDE5-Is are limited.

Objective

To compare the efficacy and safety of different classes of oral PDE5-Is for ED.

Evidence acquisition

A systematic search was performed in PubMed, Cochrane Library, and Embase to identify randomized controlled trials that compared different PDE5-Is or PDE5-Is with a placebo for ED. The methodological quality of included studies was appraised with the Cochrane Collaboration bias appraisal tool, and the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation system.

Evidence synthesis

A total of 118 trials (31 195 individuals) were included. There was no major difference in the results between the traditional meta-analysis and the network meta-analysis. Network meta-analysis demonstrated that PDE5-Is were superior to placebo to improve erectile function. Compared with tadalafil (relative risk [RR]: 0.61; 95% confidence interval [CI], 0.33–0.90) and vardenafil (RR: 0.63; 95% CI, 0.35–0.92), avanafil was less effective on Global Assessment Questionnaire question 1. Tadalafil was more effective than vardenafil (mean difference [MD]: 1.49; 95% CI, 0.50–2.50) and udenafil (MD: −1.84; 95% CI, −3.31 to −0.33) as measured by the erectile function domain of the International Index of Erectile Function. For all efficacy outcomes, the absolute effects and the rank tests indicated that tadalafil and vardenafil were the most effective agents. After adjusting for dosage, the conclusion remained the same. Safety analysis showed there was no major difference among different agents.

Conclusions

In recommended doses, oral PDE5-Is are more effective than placebo for ED, and tadalafil seems to be the most effective agent, followed by vardenafil. PDE5-Is are generally safe and well tolerated, and there is no major difference on the safety profile.     

Exploration of the association between chronic periodontal disease and erectile dysfunction from a population‐based view point

Several cross‐sectional studies have indicated an association between chronic periodontal disease (CPD) and cardiovascular disease and metabolic syndrome. Erectile dysfunction (ED) also shares pathological mechanisms with these diseases. Using a nationwide population‐based data set, we examined the association between ED and CPD and assessed the effect of dental extraction (DE) on ED prevalence in different aged CPD populations in Taiwan. We identified 5105 patients with ED and randomly selected 10 210 patients as controls. Of these patients, 2617 (17.09%) were diagnosed with CPD according to the index data: 1196 (23.43%) in the ED group and 1421 (13.92%) in the control group. After adjusting for comorbid factors, patients with ED were more likely to have been diagnosed with prior CPD than controls (OR = 1.79, 95% CI = 1.64–1.96, P < 0.001). Moreover, the association was much stronger in the populations aged less than 30 years (OR = 2.13, 95% CI = 1.23–3.70, P < 0.001) and more than 59 years (OR = 2.27, 95% CI = 1.99–2.59, P < 0.001). Dental extraction seems to attenuate damage to the penile endothelial beds caused by CPD‐related inflammation and overcame the process of ED in the middle‐aged and older populations.     

Comparison of erectile function in patients with end-stage renal disease receiving haemodialysis and kidney transplantation

To investigate the frequency and risk factors of ED in haemodialysis patients (HDps) and kidney transplantation (KTx) recipients (KTxRs). HDps and KTxRs between the ages of 18–65 were compared in terms of ED. IEFF-15 (International Index of Erectile Function) score was used to evaluation of ED. Fifty-seven male HDps and 52 male KTxRs with a mean age of 45.6 ± 10.4 years were included in our study. DM, CAD, hyperlipidaemia, smoking and beta blocker use were higher HDps (p = 0.037, p < 0.001, p = 0.001, p = 0.001 and p = 0.031 respectively). There was no ED in five (8.8%) HDps and 27(51.9%) KTxRx. Severity of ED was significantly higher in HDps (p < 0.001). In multiple logistic regression analysis, KTx was found the most relevant associated factor with ED. KTxRs had decreased risk for ED (OR = 0.09, 95% CI 0.02–0.30, p < 0.001). ED is significantly more common in HDps than KTxRs. Known risk factors for ED, HT, DM, CAD, HL, smoking, obesity and beta-blocker use were not related to ED in the HDps and KTxRs, and the KTx was positively effective for ED in patients undergoing renal replacement therapy.     

Long‐term outcomes of antithymocyte globulin in patients with hematological malignancies undergoing myeloablative allogeneic hematopoietic cell transplantation: a systematic review and meta‐analysis

Antithymocyte globulin (ATG) has shown efficacy in preventing acute GVHD (aGVHD) in allogeneic hematopoietic cell transplantation (allo‐HCT), but its efficacy in chronic GVHD (cGVHD) and long‐term outcomes remains controversial. We conducted a systematic review and meta‐analysis to evaluate potential benefit and risk of prophylactic ATG use in myeloablative HCT. We searched Pubmed, EMBASE, Cochrane databases, and included 10 trials (two RCTs and eight retrospective) comparing ATG use vs. control with a total of 1859 patients. The median follow‐ups were over two yr. Outcomes assessed included overall cGVHD, extensive cGVHD, overall survival (OS), disease‐free survival, relapse, and causes of death. Our results showed ATG significantly decreased overall cGVHD (RR = 0.59; 95% CI: 0.53–0.66, p < 0.00001), extensive cGVHD (RR = 0.34; 95% CI: 0.25–0.47, p < 0.00001). Pooled results also showed ATG use was associated with a marginal increased risk of relapse (RR = 1.28; 95% CI: 1.01–1.63, p = 0.04), and a non‐inferior OS (HR = 0.86; 95% CI: 0.74–1.01, p = 0.06). We conclude prophylactic use of ATG exerts a favorable effect in reducing cGVHD without survival impairment in a long term, although a higher relapse rate is a major threat.     

Testosterone undecanoate improves erectile dysfunction in hypogonadal men with the metabolic syndrome refractory to treatment with phosphodiesterase type 5 inhibitors alone

At least 30–35% of men with erectile dysfunction (ED) fail to respond to treatment with phosphodiesterase type 5 (PDE‐5) inhibitors. Testosterone (T) has effects not only on sexual desire, but also on the anatomical and physiological substrate of erection. This study analysed the effects of T administration to men unsuccessfully treated for ED with PDE‐5 inhibitors only. Twenty‐nine men aged 36–75 years (mean 59 years) with ED were studied. They suffered from ED for a mean of 2.7 years and had subnormal plasma T levels (total T <3.5 ng ml^?1). They received parenteral testosterone undecanoate for 102 weeks. Changes of the domains of the International Index of Erectile Function (IIEF) were assessed. After 6 weeks of T treatment, the sexual desire domain of IIEF had improved (from 4.1 ± 1.4 to 7.2 ± 1.7) and erectile function as measured by IIEF started to improve, reaching a plateau after 30 weeks (from 9.1 ± 2.1 to 26.5 ± 2.3). Features of the metabolic syndrome also improved. There were no adverse effects of T administration. Addition of T to treatment of hypogonadal men unsuccessfully treated with PDE‐5 inhibitors only, appeared useful and acceptably safe.