Nutraceutical interventions for erectile dysfunction: a systematic review and network meta-analysis.

BACKGROUND: Although nutraceutical-based treatments are often offered for erectile dysfunction (ED), their efficacy remains doubtful, and the choice of one substance over the other is challenged by the dearth of head-to-head comparative studies. AIM: We aimed to compare the efficacy of available nutraceutical interventions, alone or in combination with phosphodiesterase type 5 inhibitors (PDE5i), in improving erectile function in men with ED through a network meta-analysis (NMA), which incorporates direct and indirect evidence into one model thus generating a hierarchy of effectiveness. METHODS: PubMed, Scopus, Web of Sciences, and Cochrane Library databases were searched for randomized placebo-controlled trials (RCTs) assessing the effect of any nutraceutical regimen in improving erectile function when compared to each other, placebo, and/or PDE5i in men with ED. Data were included in a random-effects NMA, where efficacy of treatments was ranked by surface under the cumulative ranking curve (SUCRA). Two NMAs were also conducted separately for organic and non-organic ED. Reciprocal comparisons between all treatments were analyzed by league tables. OUTCOMES: The main outcome was the standardized mean difference in the score of the International Index of Erectile Function (IIEF)-5 or IIEF-6. RESULTS: Fifteen RCTs provided information on 1000 men with ED. In the overall NMA, compared to placebo, the combination propionyl L-carnitine (PLC) + acetyl L-carnitine (ALC) + Sildenafil was associated with the highest SUCRA (97%) in improving erectile function score, followed by L-Arginine + Tadalafil (84%), Sildenafil (79%), Tadalafil (72%), and L-Arginine (52%). No other treatment regimen showed efficacy with statistical significance. In patients with organic ED, the efficacy of Sildenafil and Tadalafil was significantly improved by PLC + ALC and L-Arginine, respectively. On the contrary, in non-organic ED, nutraceuticals did not improve the therapeutic performance of daily Tadalafil. CLINICAL IMPLICATIONS: This NMA contributes valuable insights into the potential of nutraceutical interventions for ED. STRENGTHS AND LIMITATIONS: We employed strict inclusion criteria related to study design and diagnostic tool, ensuring the assumption of transitivity and the consistency of the analysis. CONCLUSION: Against a background of general ineffectiveness of most nutraceutical interventions, L-Arginine and the mix PLC + ALC appeared to be of some usefulness in improving erectile function, especially in combination with PDE5i in organic ED.

Analysis of evidence on nutraceutical interventions for Peyronie's disease: a guideline-based critical review.

INTRODUCTION: The management of Peyronie's disease (PD) is a challenge for the clinician. Despite the lack of etiologic therapy, different nonsurgical approaches have often been empirically proposed. The most used treatment is based on nutraceutical drugs with antioxidant activity, although such an intervention remains controversial. OBJECTIVES: We reviewed the evidence from the randomized controlled trials included in the recommendations of the American Urological Association (AUA), Canadian Urological Association (CUA), European Association of Urology, and International Society for Sexual Medicine. METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane Library for randomized controlled trials, reviews, and guidelines on nutraceutical interventions for PD. RESULTS: Our analysis provides detailed information on potential interventions, underlying the inconsistent evidence. Acetyl esters of carnitine, although not recommended by any of the available guidelines, showed potential benefit in some selected studies. Omega-3 fatty acids are not recommended due to withdrawn study evidence. The CUA and AUA were the only societies to consider the use of coenzyme Q10. While the CUA suggested that it might be offered as a treatment option, the AUA refrained from taking a definitive stance due to insufficient evidence. Similarly, conflicting recommendations have been produced on potassium para-aminobenzoate. While the CUA considers potassium para-aminobenzoate potentially useful in slowing PD progression, the AUA deems the evidence insufficient. Conversely, both the International Society for Sexual Medicine and European Association of Urology do not recommend its use. CONCLUSION: This critical comparative analysis of the most recent guidelines produced by the leading scientific societies highlights some inconsistencies in the recommendations on nutraceutical intervention for PD, even within a background of overall ineffectiveness of this treatment approach.

Which PDE5 inhibitor is the most effective in the treatment of erectile dysfunction in men with spinal cord injury? A systematic review and network meta-analysis.

BACKGROUND: Phosphodiesterase 5 inhibitors (PDE5i) are the first-line drugs for erectile dysfunction (ED) but differences among available molecules should drive therapy personalization. Choosing one PDE5i over another is a challenge in men with spinal cord injury (SCI), as the evidence of efficacy for each molecule is derived from few studies and comparative "head-to-head" trials are lacking. OBJECTIVE: To assess the efficacy of the different PDE5i for SCI-related ED with a network meta-analysis (NMA) approach. MATERIALS AND METHODS: Databases from PubMed, Web of Science, Scopus, and Cochrane Library were checked for randomized controlled trials (RCTs) comparing any PDE5i to each other or placebo in men with traumatic SCI lasting ≥6 months. Data were incorporated in a random-effect NMA, where treatments' efficacy was ranked using the surface under the cumulative ranking curve (SUCRA). RESULTS: The 10 RCTs included provided information about 1,492 men with ED due to traumatic SCI. Intervention arms included sildenafil, tadalafil, and/or vardenafil. Overall, at the pairwise meta-analysis, PDE5i were four times more effective than placebo in improving erectile function (risk ratio: 4.13, 95% CI: 2.76, 6.19). The comparative analysis from NMA revealed that tadalafil was associated with the highest SUCRA value (81%), followed by vardenafil (68%) and sildenafil (49%). DISCUSSION AND CONCLUSION: Within the grading of comparison network, tadalafil appeared to be the best PDE5i in the treatment of SCI-related ED. Further focused studies are warranted to confirm these findings and define optimal doses and duration of therapy.