The effectiveness and safety of intracavernosal botulinum toxin injections in the management of erectile dysfunction: a systematic review and meta-analysis of clinical studies.

Background: Patients with erectile dysfunction (ED) are often left with limited nonsurgical options when conventional pharmacotherapies become ineffective. Botulinum neurotoxin serotype A (BoNT-A) intracavernosal injections (ICIs) have been demonstrated in a few clinical studies to be effective and safe in managing ED and may serve as a first- or second-line option.

Aim: To perform a systematic review and meta-analysis on the effectiveness and safety of BoNT-A ICI in managing ED with a focus on human studies.

Methods: A systematic review and meta-analysis of clinical studies was performed in accordance with the PRISMA 2020 statement. Adult men with ED who received BoNT-A were included in the study. The risk of bias assessment of included studies was performed using the JBI assessment checklists.

Outcomes: The effectiveness and safety of BoNT-A ICI. Measures of effectiveness included the increase or change in International Index for Erectile Function (IIEF-EF) score/Sexual Health Inventory for Men (SHIM) score/Erection Hardness Score (EHS) or change in Doppler ultrasound parameters and the percentage of patients achieving the minimal clinically important difference (MCID) score.

Results: The search retrieved 61 articles, and 2 randomized controlled trials (RCTs) and 4 retrospective studies met the inclusion criteria. Three types of BoNT-A were evaluated: onaBoNT-A, aboBoNT-A, and incoBoNT-A. At least 40% of the patients achieved the MCID (2-7 points increase in the IIEF-EF/SHIM score) depending on the severity of ED) at ≥1 month. When directly comparing all 3 BoNT-A, the overall response rate was 77.5%, with no statistically difference between the 3 types. For aboBoNT-A, 500 U appeared to sustain the effectiveness longer compared to 250 U. OnaBoNT-A improved peak systolic velocity on Doppler ultrasound compared with saline. Meta-analysis of the 2 RCTs demonstrated a mean difference of 4.35 (P = .008) in the SHIM score at 12 weeks in favor of onaBoNT-A over normal saline. No systemic side effects have been reported, and the only infrequent local side effect was transient penile pain. Only one case of priapism was reported.

Strengths and limitations: This is the first systematic review summarizing data from human studies on ED and BoNT-A ICI. The inclusion criteria and outcomes of the included studies varied, which limited the number of studies included and parameters assessed in the meta-analysis.

Conclusion: BoNT-A may become an acceptable non-surgical option. However, there is a lack of clinical randomized or observational studies on this topic, and more randomized studies with standardized reporting are required to replicate current results and investigate the long-term benefits of BoNT-A as a monotherapy or adjunct therapy in the management of ED.