## 3 Discussion
Specifically, incobotulinum toxin is reported to be as effective as onabotulinum toxin A, while abobotulinum toxin is less potent compared with the other two formulations [32]. Among selected papers, onaBTX-A was used by twelve studies, one used aboBTX-A, one incoBTX-A, and four did not specify this information. It is hard to make a summary on the effect of BTX-A on lower urinary tract symptoms, sexual function and quality of life changes, as well as on pain, comparing baseline and post-treatment times, mainly because the diagnostic tools to evaluate these outcomes used by the included studies are different as well as the time at which the measurements were done. Regarding secondary outcomes addressed by each study, BTX-A reduced frequency and noturia episodes associated with BPS, while data among sexual and bowel functions were poorly reported in the manuscripts. All the four studies investigating the role of BTX-A in GPP evaluated its benefit on sexual function using several tools, such as VAS scale for dyspneauria, FSFI and FSDS questionnaires and the Marinoff scale, with different results. One showed a significant difference from baseline, for VAS score evaluated dyspareunia both in the BTX-A and control groups [26], while in the study of [PERSON] et al., results from the Marinoff dyspneauria scale indicated a significant improvement only in patients who underwent BTX-A 50 IU injections in dorsal vestibule, from baseline to three months, compared with the other two arms of the study [24]. Otherwise, [PERSON] et al. demonstrated no statistically significant improvement of FSFI full score, from baseline until six months of follow up, between the two groups [22]. In addition, [PERSON] et al. showed no statistically significant difference in dysmenorrhea for either group from their baseline scores, while repeated injections of BTX-A can provide benefit for dyspneauria [23]. Finally, another aspect poorly investigated is the real prevalence and nature of adverse events/side effects. As illustrated in the Supplementary Table S13, among IC/BPS studies, the main complications associated with BTX-A injections included urinary tract infections (UTI), which sometimes required the use of antibiotics, transient voiding difficulties, that rarely required catheterization, and gross hematuria. In CP/PPS no serious or systemic complications were recorded, except for mild gross hematuria or hematospermia, while in the GPP groups urinary incontinence, injection site pain and flu-like symptoms were reported. Future studies need to standardize the way to report of the adverse events/side effects and the time of their occurrence. A recent review by [PERSON] et al. highlighted the same critical issues of our manuscript. They included 16 studies, most in common with our paper, and considered all CPPS subtypes, even chronic anal pain due to chronic anal fissure, and comprised in the analysis even a comparative retrospective study [33]. They showed that BTX-A reduced pain significantly overall in three studies, two among BPS/IC and one regards CPP/CP, while in none of the other CPPS subtypes studies, patients underwent BTX-A injection in the pelvis, experienced a statistically significant pain relief if compared to the control group [33]. We additionally performed a pooled metanalysis and moderator meta-regression analysis including only BTX-A-treated patients, who were evaluated using the VAS scale, comparing pain at baseline and at last available follow up time. We showed an improvement in pain perception in all cohorts that underwent treatment in the overall population and in specific disease populations, even if some studies did not reach a significant improvement when independently considered. No clinical factors were found to influence the treatment efficacy. However, a trend was found for the number of site injections in IC/BPS patients who underwent BTX-A injection in the bladder trigone only.