Dimitrios Kalyvianakis et al., 2024: The effect of combination treatment with low-intensity shockwave therapy and daily tadalafil on severe erectile dysfunction: a double-blind, randomized, sham-controlled clinical trial
Dimitrios Kalyvianakis 1 2 , Ioannis Mykoniatis 1 , Nikolaos Pyrgidis 2 3 , Paraskeui Kapoteli 1 , Filimon Zilotis 1 , Dimitrios Hatzichristou 1 2
1Department of Urology, Aristotle University of Thessaloniki, Thessaloniki 54635, Greece.
2Institute for the Study of Urological Diseases, Thessaloniki 54622, Greece.
3Department of Urology, University Hospital, LMU Munich, Munich 81377, Germany.
Abstract
Background: Patients with severe erectile dysfunction (ED) remain the most challenging group in terms of available noninvasive treatment modalities.
Aim: The study sought to assess the role of combination therapy with low-intensity shockwave therapy (LiST) and daily tadalafil 5 mg in a highly select group of patients with severe vasculogenic ED through a double-blind, randomized trial.
Methods: Forty-eight sexually active men were randomly assigned to 12 sessions of LiST 3 times weekly and tadalafil 5 mg once daily (n = 34) or sham therapy and tadalafil (n = 17) for 4 weeks. Patients were assessed at 1 and 3 months after completion of treatment.
Outcomes: Improvement of erectile function was evaluated through the International Index of Erectile Function-Erectile Function domain (IIEF-EF) or 6-item IIEF and the Sexual Encounter Profile (SEP) diary. The primary outcome was the difference between the groups in the IIEF-EF at 3 months after completion of treatment. Secondary outcomes comprised (1) the difference between the groups in the IIEF-EF at 1 month after completion of treatment, (2) the difference between the groups in the "yes" responses to question 3 of the SEP diary at 1 and 3 months, and (3) the treatment-related adverse events. The number of patients attaining a minimal clinically important difference in the IIEF-EF (improvement of at least 7 points) was also assessed.
Results: After treatment, the absolute scores in the IIEF-EF were higher in patients receiving LiST and tadalafil vs sham therapy and tadalafil both at the 1-month (12.1 ± 2.4 vs 10.2 ± 1.7; P = .002) and at the 3-month (12.9 ± 2.1 vs 10.8 ± 1.8; P < .001) evaluation. Between the 2 groups, the proportion of "yes" responses to question 3 of the SEP diary was not statistically significant, whereas the number of patients attaining a minimal clinically important difference in the IIEF-EF was statistically significant only at the 3-month evaluation. No adverse events occurred.
Clinical implications: Application of LiST in patients with severe vasculogenic ED receiving daily dose tadalafil may further improve erectile function compared with tadalafil as a stand-alone treatment on the short term.
Strengths and limitations: Although we provided the first study in the field, severe vasculogenic ED was defined based on medical history and clinical examination and not based on penile ultrasound measures.
Conclusion: The combination of 12 sessions LiST 3 times weekly and daily tadalafil for 4 weeks led to a 2-point difference in the IIEF-EF compared with sham therapy and daily tadalafil among patients with severe vasculogenic ED after 1 and 3 months from completion of treatment.
J Sex Med. 2024 Apr 10:qdae038. doi: 10.1093/jsxmed/qdae038. Online ahead of print.
PMID: 38600694
Comments 1
This study investigates the combined effect of low-intensity shockwave therapy (LiST) and daily tadalafil (5 mg) on patients with severe erectile dysfunction (ED) who are partial responders to PDE5 inhibitors. Previous research suggested that LiST is effective for mild to moderate ED, but there has been limited data on severe cases.
Study Design:
Conducted as a double-blind, randomized, sham-controlled trial at Aristotle University. Participants: 51 patients aged 40-70 with severe vasculogenic ED. They were divided into two groups (LiST + tadalafil vs. sham + tadalafil) and underwent 12 sessions of LiST or sham treatment, 3 times weekly for 4 weeks, alongside daily tadalafil.
All patients were treated by the ARIES 2 low-intensity shockwave generator and the Smart Focus probe provided by Dornier MedTech GmbH.
Results:
Primary Outcome: Improvement in the International Index of Erectile Function (IIEF-EF) at 3 months post-treatment.
LiST + tadalafil group had significantly higher IIEF-EF scores at 1 month (12.1 vs 10.2) and 3 months (12.9 vs 10.8) compared to the sham + tadalafil group.
However, no significant differences were found in the proportion of successful intercourse attempts between the groups. This means, that the difference was not clinically significant.
Secondary Outcomes: By 3 months, 18% of the LiST + tadalafil group saw clinically important improvements, compared to 0% in the sham group. No major adverse events occurred. This underlines, that one has to be patient, when evaluating the results. 1 Month is certainly too short.
Conclusion:
The combination of LiST and tadalafil showed short-term improvement in severe ED, particularly in IIEF-EF scores, but further studies with longer follow-up and larger sample sizes are needed. The therapy is suggested as a non-invasive option for difficult-to-treat cases, although its long-term effectiveness is still unclear. We hope, that this study will present follow-up results. The design of the study should be able to provide further important information about this treatment option.
Jens Rassweiler