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Intra-Cavernosal Injection of Botulinum Toxin in the Treatment of Erectile Dysfunction: a Systematic Review and Meta-Analysis

Published:September 14, 2022DOI:https://doi.org/10.1016/j.urology.2022.08.039

      OBJECTIVE

      To evaluate the role of botulinum toxin in treating erectile dysfunction as a novel treatment strategy avoiding morbid and irreversible surgeries.

      METHODS

      A systematic review of literature was conducted from January 1990 through July 31, 2021. Search engines used included PubMed, Embase and Medline databases, to identify studies investigating botulinum toxin in erectile dysfunction, published in English. Seven studies in total were included in our review including two pre-clinical studies. A meta-analysis was performed on three outcomes included commonly in at least two studies. Among the different parameters assessed were, Erection Hardness Score (EHS), Peak Systolic Velocity in cavernosal artery (PSV) and the Sexual Health Inventory for Men (SHIM) score.

      RESULTS

      A clear benefit was noted for intracavernosal injection (ICI) of botulinum toxin (BoNT-A) on PSV with a mean difference (MD) of 10.82 [4.99, 16.65] and a heterogeneity of I2=61%. EHS results favored BoNT-A as well over placebo with a MD of 0.7 [0.47, 0.93] and heterogeneity of I2=94%. As for SHIM score, with a heterogeneity of I2=85%, no statistically significant difference was found (MD 0.58 [-0.03, 1.20]).

      CONCLUSION

      Our review and meta-analysis have shown statistical significance for the benefit of BoNT-A in terms of EHS and PSV. However, this statistical significance should be interpreted in light of the given limitations: small sample size, heterogeneity in data collection, patient selection bias, and clinical significance of the measured differences. ICI of BoNT-A should currently be limited to clinical studies to further elucidate its clinical benefit.
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      References

        • Kessler A.
        • Sollie S.
        • Challacombe B.
        • Briggs K.
        • Van Hemelrijck M.
        The global prevalence of erectile dysfunction: a review.
        BJU Int. 2019; 124
        • Kim M.M.
        • Harvey J.
        • Gusev A.
        • Norton J.M.
        • Miran S.
        • Bavendam T.
        A scoping review of the economic burden of non-cancerous genitourinary conditions.
        Urology. 2021; (S0090–4295(21)00981-X)
        • Rezaee M.E.
        • Ward C.E.
        • Brandes E.R.
        • Munarriz R.M.
        • Gross M.S.
        A review of economic evaluations of erectile dysfunction therapies.
        Sex Med Rev. 2020; 8: 497-503
        • Salonia A.
        • et al.
        European Association of Urology guidelines on sexual and reproductive health-2021 update: male sexual dysfunction.
        Eur Urol. 2021; 80: 333-357
        • Terentes-Printzios D.
        • Ioakeimidis N.
        • Rokkas K.
        • Vlachopoulos C.
        Interactions between erectile dysfunction, cardiovascular disease and cardiovascular drugs.
        Nat Rev Cardiol. 2022; 19: 59-74
        • MacDonald S.M.
        • Burnett A.L.
        Physiology of erection and pathophysiology of erectile dysfunction.
        Urol Clin North Am. 2021; 48: 513-525
        • Thomas C.
        • Konstantinidis C.
        Neurogenic erectile dysfunction. Where do we stand?.
        Med (Basel, Switzerland. 2021; 8: 3
        • Madeira C.R.
        • et al.
        Efficacy and safety of oral phosphodiesterase 5 inhibitors for erectile dysfunction: a network meta-analysis and multicriteria decision analysis.
        World J Urol. 2021; 39: 953-962
        • Yuan J.
        • et al.
        Comparative effectiveness and safety of oral phosphodiesterase type 5 inhibitors for erectile dysfunction: a systematic review and network meta-analysis.
        Eur. Urol. 2013; 63: 902-912
        • Duncan C.
        • Omran G.J.
        • Teh J.
        • Davis N.F.
        • Bolton D.M.
        • Lawrentschuk N.
        Erectile dysfunction: a global review of intracavernosal injectables.
        World J Urol. 2019; 37: 1007-1014
        • Lokeshwar S.D.
        • Patel P.
        • Shah S.M.
        • Ramasamy R.
        A systematic review of human trials using stem cell therapy for erectile dysfunction.
        Sex Med Rev. 2020; 8: 122-130
        • Angulo J.C.
        • Arance I.
        • de Las Heras M.M.
        • Meilán E.
        • Esquinas C.
        • Andrés E.M.
        Efficacy of low-intensity shock wave therapy for erectile dysfunction: a systematic review and meta-analysis.
        Actas Urol. Esp. 2017; 41: 479-490
        • Carvajal A.
        • Benavides J.
        • García-Perdomo H.A.
        • Henry G.D.
        Risk factors associated with penile prosthesis infection: systematic review and meta-analysis.
        Int J Impot Res. 2020; 32: 587-597
      1. J. R. Barr et al., “Botulinum Neurotoxin Detection and Differentiation by Mass Spectrometry - Volume 11, Number 10—October 2005 - Emerg Infect Dis.”

        • Reddy A.G.
        • Dick B.P.
        • Natale C.
        • Akula K.P.
        • Yousif A.
        • Hellstrom W.J.G.
        Application of Botulinum Neurotoxin in Male Sexual Dysfunction: Where Are We Now?.
        Sex Med Rev. 2021; 9
      2. Fda and Cder, “NDA/BLA Multi-Disciplinary Review and Evaluation: BOTOX”

        • Naumann M.
        • Jankovic J.
        Safety of botulinum toxin type A: a systematic review and meta-analysis.
        Curr Med Res Opin. 2004; 20
        • Giuliano F.
        • Brock G.
        Botox for erectile dysfunction.
        J Sex Med. 2017; 14
        • Page M.J.
        • et al.
        The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.
        BMJ. 2021; 372 (n): 71
        • Higgins J.P.
        • Altman D.G.
        Assessing Risk of Bias in Included Studies.
        Cochrane Handb Syst Rev Interv Cochrane B Ser. Sep. 2008; : 187-241
        • Cappelleri J.C.
        • Rosen R.C.
        The Sexual Health Inventory for Men (SHIM): a 5-year review of research and clinical experience.
        Int J Impot Res. May 2005; 17 (2005 174): 307-319
        • Ramanathan R.
        • et al.
        Predictive correlation between the International Index of Erectile Function (IIEF) and Sexual Health Inventory for Men (SHIM): implications for calculating a derived SHIM for clinical use.
        J. Sex. Med. 2007; 4: 1336-1344
        • De Young L.
        • Campbell J.
        • Radomski S.
        • Alzubaidi R.
        • Brock G.
        142 intracavernosal injection of botulinum toxin to improve erectile function in older rats.
        J Sex Med. Jan. 2017; 14: S40-S41
        • Ghanem H.
        • Fathy I.
        • Raheem A.A.
        • Shamloul R.
        • Hamid M.A.
        024 The effect of botulinum toxin on penile vascular parameters and clinical outcome in patients with severe ed: a pilot study.
        J Sex Med. Jan. 2017; 14: S11
        • Ghanem H.
        • Raheem A.A.
        • AbdelRahman I.F.S.
        • Johnson M.
        • Abdel-Raheem T.
        Botulinum neurotoxin and its potential role in the treatment of erectile dysfunction.
        Sex Med Rev. Jan. 2018; 6: 135-142
        • G F
        • J C
        • D P
        Safety and efficacy of intracavernosal injections of AbobotulinumtoxinA (Dysport ®) as add on therapy to phosphosdiesterase type 5 inhibitors or prostaglandin E1 for erectile dysfunction-case studies.
        Toxins (Basel). May 2019; 11
        • Taleb A.A.
        • El-Tabey M.
        • El-Shaer W.A.
        • Ghanem H.M.
        • Wahab T.A.
        Comparative study between intracavernosal injection of botulinum toxin type A [50 and 100 unit], efficacy and durability in the treatment of vascular erectile dysfunction.
        Benha J. Appl. Sci. 2019; : 31-35
        • El-Shaer W.
        • Ghanem H.
        • Diab T.
        • Abo-Taleb A.
        • Kandeel W.
        Intra-cavernous injection of BOTOX® (50 and 100 Units) for treatment of vasculogenic erectile dysfunction: Randomized controlled trial.
        Andrology. 2021; 9: 1166-1175
      3. “Intracavernosal Injection of Botulinum Toxin Type A in the Treatment of Vascular Erectile Dysfunction - Full Text View - ClinicalTrials.gov.” [Online]. Available: https://clinicaltrials.gov/ct2/show/NCT02584686. [Accessed: 05-Feb-2022].

      4. “Botulinum Toxin for Erectile Dysfunction - Full Text View - ClinicalTrials.gov.” [Online]. Available: https://clinicaltrials.gov/ct2/show/NCT03102762. [Accessed: 05-Feb-2022].

      5. “Intracavernous Injection of Botox 100 U for Treatment of PDE5Is Inconvenient Patients With ED - Full Text View - ClinicalTrials.gov.” [Online]. Available: https://clinicaltrials.gov/ct2/show/NCT04172558. [Accessed: 17-Jul-2022].

        • Copel L.
        • Katz R.
        • Blachar A.
        • Sosna J.
        • Sheiman R.G.
        Clinical and duplex US assessment of effects of sildenafil on cavernosal arteries of the penis: comparison with intracavernosal injection of vasoactive agents–initial experience.
        Radiology. Dec. 2005; 237: 986-991
        • Said S.Z.
        • Nasser T.A.
        • Ayad M.
        • Motawi A.T.
        Evaluation of the sensitivity of different doses of vasoactive drugs in diagnosing erectile dysfunction in impotent patients: a prospective case-control study,” Cent.
        Eur J Urol. 2021; 74: 109
        • El-Sakka A.I.
        What is the current role of intracavernosal injection in management of erectile dysfunction?.
        Int J Impot Res. May 2016; 28: 88-95
        • Belew D.
        • Klaassen Z.
        • Lewis R.W.
        Intracavernosal injection for the diagnosis, evaluation, and treatment of erectile dysfunction: a review.
        Sex Med Rev. Mar. 2015; 3: 11-23
        • Sedgwick P.
        Meta-analyses: what is heterogeneity?.
        BMJ. Mar. 2015; 350