Gallo L. et al., 2022: Adjuvant daily therapy with L-arginine 2,500 mg and tadalafil 5 mg increases efficacy and duration of benefits of low-intensity extracorporeal shock wave therapy for erectile dysfunction: A prospective, randomized, single-blinded study with 1-year follow-up

Tuesday, 24 May 2022

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Gallo L, Pecoraro S, Sarnaccharo P.
Gallo Uro-Andrology Centre, Naples, Italy.
Division of Urology, Malzoni Clinic, Avellino, Italy.
Department of Economics and Management, "Federico II" University, Naples, Italy.

Abstract

Purpose: To investigate a therapeutic protocol for erectile dysfunction (ED) based on the combination of low-intensity extracorporeal shock wave therapy (Li-ESWT), tadalafil, and L-arginine.

Materials and methods: Recruited patients completed the International Index of Erectile Function erectile function domain (IIEF-EF) and the Erection Hardness Score (EHS) questionnaires at baseline and were randomly assigned in two groups: A (treatment group) and B (control group). Men in both groups received six weekly applications of Li-ESWT. Group A was prescribed adjuvant oral therapy with tadalafil 5 mg and L-arginine 2,500 mg. Follow-up visits were scheduled 1, 6, and 12 months after the last Li-ESWT application. At each follow-up visit, the IIEF-EF and EHS questionnaires were administered again. The main outcome measures were the changes from baseline to every follow-up visit in IIEF-EF and EHS scores.

Results: The mean IIEF-EF score in group A was 16.0±4.0, 24.8±3.4, 23.3±4.6, and 21.6±5.5 at baseline, 1, 6, and 12 months of follow-up, respectively, whereas in group B the mean IIEF-EF score was 16.5±4.1, 22.7±4.2, 21.5±4.5, and 19.5±4.9, respectively. We reported an increase in the mean EHS score in group A from 2.07±0.72 at baseline to 3.39±0.59, 3.17±0.67, and 2.98±0.72 at 1, 6, and 12 months, respectively, and in group B from 2.12±0.80 at baseline to 3.07±0.78 and 2.95±0.76 at 1 and 6 months, respectively.

Conclusions: Adjuvant daily therapy with L-arginine 2,500 mg and tadalafil 5 mg was safe and effective in increasing the efficacy and the duration of benefits of Li-ESWT.
Investig Clin Urol. 2022 Jan;63(1):83-91. doi: 10.4111/icu.20210317. PMID: 34983126. FREE ARTICLE

Comments 1

Jens Rassweiler on Tuesday, 24 May 2022 10:30

Low- intensity extracorporeal shock wave therapy (Li-ESWT) has been demonstrated by several meta-analyses to be an effective and safe treatment for ED of various etiologies and has been included as a first-line therapy for this disease in the latest guidelines of the European Association of Urology for treatment of vasculogenic ED. This two-arm, prospective, randomized, single-blind trial was designed to answer the following questions:

1) What are the long-term results of Li-ESWT?

2) Are there any adjuvant therapies capable of increas- ing the benefits of Li-ESWT and making the results more lasting?

These are both very interesting questions. There is no doubt, that we have to learn and understand more of the impact of Li-ESWT on erectile dysfunction.

Li-ESWT was performed by use of the focused shock wave electromagnetic generator Duolith SD1 T-TOP (Storz Medical AG, Tägerwilen, Switzerland). Each session consisted of 3,000 shock waves delivered at an energy density of 0.25 mJ/mm2 and an emission frequency of 4 Hz. The penis was divided into six areas:1) right base shaft, 2) left base shaft, 3) right distal shaft, 4) left distal shaft, 5) right crura, and 6) left crura. Each area received 500 shock waves. All patients received 6 weekly treatments.

Individuals included in group A (treatment group) received concomitantly with the first application of Li- ESWT the prescription of adjuvant oral therapy with daily tadalafil 5 mg for 3 months and daily L-arginine 2,500 mg for 6 months. Men in group B (control group) received only Li-ESWT without oral therapy and were informed that the use of PDE-5 inhibitors was prohibited during the study. Out of 100 randomized patients, 83 were eligible (Group A: 41; Group B: 42). Observation time was 12 months.

The percentage of men who reached a minimally clinical important difference (MCID) was 100% and 88.1% at 1 month, 87.8% and 76.2% at 6 months, and 75.6% and 66.7% after 1 year for group A and group B, respectively. This means, that there was a continuous decline of the initial effect over the period of follow-up. The combination of Li-ESWT with oral medication (PDE-5-inhibitor) was always superior to the Li-ESWT alone.

Li-ESWT was introduced precisely with the aim of over- coming the limits of oral therapy: to make the pathologic processes underlying ED reversible and, above all, to be a definitive therapeutic approach with stable and lasting results. Obviously, the application of six sessions over six weeks might not be enough to create a plateau of response. This is not altered by additional oral medication. These results are in-line with the current literature.

The authors already mention one major limitation of the study: There is no Placebo-group. Moreover, the authors should have used only one drug (i.e. only tadalafil 5 mg), but probably over a longer period of time. Based on these two limitations, the results of this study provide more questions than answers. They could show, that the effect of a single six-week course of Li-ESWT can be effective and probably enhanced by administration of 5mg Tadalafil. However, since there was no placebo-group, the exact improvement remains uncertain. Future study should test a Li-ESWT-maintenance (ie. 2 treatment / week every 3 months), similar to the BCG-instillation therapy for superficial bladder cancer.

1) What are the long-term results of Li-ESWT?

2) Are there any adjuvant therapies capable of increas- ing the benefits of Li-ESWT and making the results more lasting?

These are both very interesting questions. There is no doubt, that we have to learn and understand more of the impact of Li-ESWT on erectile dysfunction.

Li-ESWT was performed by use of the focused shock wave electromagnetic generator Duolith SD1 T-TOP (Storz Medical AG, Tägerwilen, Switzerland). Each session consisted of 3,000 shock waves delivered at an energy density of 0.25 mJ/mm2 and an emission frequency of 4 Hz. The penis was divided into six areas:1) right base shaft, 2) left base shaft, 3) right distal shaft, 4) left distal shaft, 5) right crura, and 6) left crura. Each area received 500 shock waves.  All patients received 6 weekly treatments.

Individuals included in group A (treatment group) received concomitantly with the first application of Li- ESWT the prescription of adjuvant oral therapy with daily tadalafil 5 mg for 3 months and daily L-arginine 2,500 mg for 6 months. Men in group B (control group) received only Li-ESWT without oral therapy and were informed that the use of PDE-5 inhibitors was prohibited during the study. Out of 100 randomized patients, 83 were eligible (Group A: 41; Group B: 42). Observation time was 12 months.

The percentage of men who reached a minimally clinical important difference (MCID) was 100% and 88.1% at 1 month, 87.8% and 76.2% at 6 months, and 75.6% and 66.7% after 1 year for group A and group B, respectively. This means, that there was a continuous decline of the initial effect over the period of follow-up. The combination of Li-ESWT with oral medication (PDE-5-inhibitor) was always superior to the Li-ESWT alone.

Li-ESWT was introduced precisely with the aim of over- coming the limits of oral therapy: to make the pathologic processes underlying ED reversible and, above all, to be a definitive therapeutic approach with stable and lasting results.  Obviously, the application of six sessions over six weeks might not be enough to create a plateau of response. This is not altered by additional oral medication. These results are in-line with the current literature.

The authors already mention one major limitation of the study: There is no Placebo-group. Moreover, the authors should have used only one drug (i.e. only tadalafil 5 mg), but probably over a longer period of time. Based on these two limitations, the results of this study provide more questions than answers. They could show, that the effect of a single six-week course of Li-ESWT can be effective and probably enhanced by administration of 5mg Tadalafil. However, since there was no placebo-group, the exact improvement remains uncertain. Future study should test a Li-ESWT-maintenance (ie. 2 treatment / week every 3 months), similar to the BCG-instillation therapy for superficial bladder cancer.

Low- intensity extracorporeal shock wave therapy (Li-ESWT) has been demonstrated by several meta-analyses to be an effective and safe treatment for ED of various etiologies and has been included as a first-line therapy for this disease in the latest guidelines of the European Association of Urology for treatment of vasculogenic ED. This two-arm, prospective, randomized, single-blind trial was designed to answer the following questions: 1) What are the long-term results of Li-ESWT? 2) Are there any adjuvant therapies capable of increas- ing the benefits of Li-ESWT and making the results more lasting? These are both very interesting questions. There is no doubt, that we have to learn and understand more of the impact of Li-ESWT on erectile dysfunction. Li-ESWT was performed by use of the focused shock wave electromagnetic generator Duolith SD1 T-TOP (Storz Medical AG, Tägerwilen, Switzerland). Each session consisted of 3,000 shock waves delivered at an energy density of 0.25 mJ/mm2 and an emission frequency of 4 Hz. The penis was divided into six areas:1) right base shaft, 2) left base shaft, 3) right distal shaft, 4) left distal shaft, 5) right crura, and 6) left crura. Each area received 500 shock waves. All patients received 6 weekly treatments. Individuals included in group A (treatment group) received concomitantly with the first application of Li- ESWT the prescription of adjuvant oral therapy with daily tadalafil 5 mg for 3 months and daily L-arginine 2,500 mg for 6 months. Men in group B (control group) received only Li-ESWT without oral therapy and were informed that the use of PDE-5 inhibitors was prohibited during the study. Out of 100 randomized patients, 83 were eligible (Group A: 41; Group B: 42). Observation time was 12 months. The percentage of men who reached a minimally clinical important difference (MCID) was 100% and 88.1% at 1 month, 87.8% and 76.2% at 6 months, and 75.6% and 66.7% after 1 year for group A and group B, respectively. This means, that there was a continuous decline of the initial effect over the period of follow-up. The combination of Li-ESWT with oral medication (PDE-5-inhibitor) was always superior to the Li-ESWT alone. Li-ESWT was introduced precisely with the aim of over- coming the limits of oral therapy: to make the pathologic processes underlying ED reversible and, above all, to be a definitive therapeutic approach with stable and lasting results. Obviously, the application of six sessions over six weeks might not be enough to create a plateau of response. This is not altered by additional oral medication. These results are in-line with the current literature. The authors already mention one major limitation of the study: There is no Placebo-group. Moreover, the authors should have used only one drug (i.e. only tadalafil 5 mg), but probably over a longer period of time. Based on these two limitations, the results of this study provide more questions than answers. They could show, that the effect of a single six-week course of Li-ESWT can be effective and probably enhanced by administration of 5mg Tadalafil. However, since there was no placebo-group, the exact improvement remains uncertain. Future study should test a Li-ESWT-maintenance (ie. 2 treatment / week every 3 months), similar to the BCG-instillation therapy for superficial bladder cancer.

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