Comparison of adverse effects of combined and isolated substances in Intracavernosal injection: a systematic review and meta-analysis

Erectile dysfunction (ED) is a highly prevalent condition that significantly impairs quality of life, and while intracavernosal injection (ICI) therapy remains an effective treatment option, it is frequently associated with adverse effects such as pain, priapism, and penile fibrosis.

The aim of this study was to review observational and randomized studies and compare the adverse effects of intracavernosal injection therapy using isolated and combined substances.

Observational and randomized studies published up to November 11, 2024 were searched in Medline (PubMed), EMBASE, and Cochrane Library. Twelve studies were included in the review, of which 5 were randomized clinical trials (RCTs) and 7 were non-RCTs, and of these 9 were included in meta-analysis. All of them evaluate the presence of side effects when administering drugs via ICI.

The primary outcomes were adverse effects, including pain, priapism, and fibrosis.

As results, the variable "pain" did not show a significant difference between the groups (OR: 0.68, 95% CI: 0.03-18.14, P = 0.82). "Priapism" had a significant result when analyzing all articles together, having minimal presence in the isolated group (OR: 1.84, 95% CI: 1.03-3.20, P = 0.04), however when analyzing only the RCTs there was no significant difference between the groups. Only four studies analyzed fibrosis as an outcome, with rates ranging from 0.8% to 15%. Notably, only two studies assessed fibrosis separately between the "combined drugs" and "isolated" groups, reporting varying rates across these categories. Clinical implications: These findings emphasize the need for individualized treatment strategies in intracavernosal therapy, as no consistent advantage was observed for combination therapy over monotherapy in minimizing adverse effects.

The main limitations of this study were the small number of available articles and the lack of more recent publications on the topic.

This study reviewed the main adverse effects of intracavernosal injection therapy for ED, emphasizing the need for a personalized approach, as no significant differences were observed between monotherapy and combination therapy regarding pain, fibrosis, and priapism.