L-arginine, tadalafil boost Li-ESWT effect for ED

In men with erectile dysfunction (ED), adjuvant daily oral therapy with L-arginine and tadalafil was effective and safe in enhancing the efficacy and duration of benefits of low-intensity extracorporeal shockwave therapy (Li-ESWT), a study has shown.

PDE5is* are considered first-line therapy for ED. [uroweb.org/guideline/sexual-and-reproductive-health, accessed March 13, 2022] “However, although very effective, oral therapy is burdened by various complications and limitations,” said the researchers. Apart from their transient and palliative effect, they reduce the spontaneity of intercourse by somehow forcing men to plan their sexual activity.

Moreover, PDE5is are costly, ineffective for some, have contraindications, and are associated with adverse effects. “All these elements lead a considerable proportion of men to abandon oral therapy. Thus, the main limitation of oral therapy remains – it is not a lasting and definitive cure for ED,” they continued.

To overcome the limits of oral therapy, Li-ESWT was introduced and has been included in the first-line treatment arsenal for ED. [Int J Impot Res 2019;31:177-194; Actas Urol Esp 2017;41:479-490] However, its effects apparently wane over time, compelling men to consider other alternatives or even more invasive options, the researchers noted.

In view of evidence reflecting the effect of Li-ESWT, PDE5i, and L-arginine combined, the researchers sought to evaluate this therapeutic protocol in 100 men (mean age 50 years) with mild (IIEF-EF score 18–25) or moderate ED (IIEF-EF score 11–17). Participants were randomized 1:1 to receive six weekly applications of Li-ESWT with (arm A) or without (arm B) tadalafil 5 mg for 3 months and L-arginine 2,500 mg for 6 months. [Investig Clin Urol 2022;63:83-91]

At all three follow-up timepoints (1, 6, and 12 months), mean IIEF-EF** scores improved from baseline in arm B (from 16.5 to 22.7, 21.5, and 19.5, respectively), more so in arm A (from 16.0 to 24.8, 23.3, and 21.6, respectively). Comparisons between arms A and B yielded p values of 0.007, 0.037, and 0.034 for the respective follow-up visits.

For EHS***, improvements from baseline were seen across all follow-up timepoints in arms A (from 2.07 to 3.39, 3.17, and 2.98 at the respective 1-, 6-, and 12-month follow-ups) and B (from 2.12 to 3.07, 2.95, and 2.76, respectively). The corresponding p values for the comparisons between arms A and B were 0.019, 0.08, and 0.08 for months 1, 6, and 12.

“All our patients reported statistically significant improvements in erectile function in terms of both IIEF-EF and EHS scores … at all follow-up visits (p<0.0001),” said the researchers.

All men in arm A achieved MCID^# at 1 month, as opposed to 88 percent of those in arm B (p=0.011). These rates dropped by months 6 and 12 but remained higher in arm A vs B (88 percent vs 76 percent; p=0.084 [6 months] and 76 percent vs 67 percent; p=0.18 [12 months]).

Only minor, infrequent adverse effects were reported. One participant in arm A discontinued treatment due to muscle pain. For Li-ESWT, some reported experiencing a stinging sensation, but this did not necessitate reducing energy density, and there were no treatment interruptions.

Nonetheless, more men appear to gravitate towards oral therapy than Li-ESWT owing to the former’s efficacy and simplicity compared with the latter. More men refused to be enrolled or did not complete Li-ESWT due to treatment cost, time constraints, satisfaction with oral therapy, and poor motivation. “Li-ESWT requires strong motivation,” said the researchers.

Given the lack of placebo arm and evaluation of haemodynamic parameters, the researchers called for further investigation on this therapeutic regimen using more, higher-frequency Li-ESWT applications. Future trials should also consider looking into the effect of the regimen in men with severe ED who remain unresponsive to medical therapy.