An update in improving erectile dysfunction therapy in Indonesia by using Li-ESWT and tadalafil combination — vascular endothelial growth factor and peak systolic velocity comparison: a randomized clinical trial
1Andrology Specialist Program, Faculty of Medicine, Universitas Airlangga – Dr. Soetomo General Aca-demic Hospital, 60286 Surabaya, Indonesia
2Department of Medical Biology, Faculty of Medicine, Universitas Indonesia, 16424 Jakarta, Indonesia
3Andrology Clinic, Dr. Soetomo General Academic Hospital, 60286 Surabaya, Indonesia
4Department of Medical Biology, Faculty of Medicine, Universitas Airlangga, 60115 Surabaya, Indonesia
5Radiology Unit, Dr. Soetomo General Academic Hospital, 60286 Surabaya, Indonesia
6Clinical Pathology Lab, Dr. Soetomo General Academic Hospital, 60286 Surabaya, Indonesia
7Department of Public Health, Faculty of Medicine, Universitas Airlangga, 60115 Surabaya, Indonesia
DOI: 10.31083/j.jomh1805118 Vol.18,Issue 5,May 2022 pp.1-8
Submitted: 09 November 2021 Accepted: 08 December 2021
Published: 31 May 2022
Background: Erectile dysfunction (ED) affects men’s life desperately and the incidence increases continuously. There are a few lines of ED therapy, but there are still many ED cases that have not treated utterly. Therefore, research is needed to obtain the most appropriate line of ED therapy, based on the underlying mechanism of ED. The aim of this study is to analyze the effect of oral daily 2.5 mg of tadalafil administration and twice weekly Low Intensity Extracorporeal Shockwave Therapy (Li-ESWT) for 4 weeks in erectile dysfunction patients, based on Peak Systolic Velocity (PSV) and Vascular Endothelial Growth Factor (VEGF). Methods: A 26-sample clinical trial was conducted with pre and post-test control group design. Random allocation was done to divide the samples into two groups. Control group was given 2.5 mg oral daily tadalafil, while the experimental group, additional twice weekly Li-ESWT was given. Therapies were given for 4 weeks. All subjects were assessed using Erection Hardness Score (EHS) score, International Index of Erectile Function (IIEF-5) score, and Color Doppler Ultrasonography (CDUS) penis for PSV, and plasma level of VEGF twice, prior to and after therapy. Results: The experimental group showed significant improvement compared to the control group in EHS (delta) 2 (1–2) vs 1 (0–2); IIEF-5 (delta) 7 (3–15) vs 4 (0–11); PSV (delta) 2.60
Erectile dysfunction; Li-ESWT; Tadalafil; PSV; VEGF
Androniko Setiawan,Andrian Japari,Rosy Nur Febriani,Silvia Werdhy Lestari,Tjahjo Djojo Tanojo,Maria Paulina Budyandini Dyah Pramesti,Agustinus Agustinus,Mu-hammad Hidayat Surya Atmaja,Munawaroh Fitriah,Budi Utomo. An update in improving erectile dysfunction therapy in Indonesia by using Li-ESWT and tadalafil combination — vascular endothelial growth factor and peak systolic velocity comparison: a randomized clinical trial. Journal of Men's Health. 2022. 18(5);1-8.
 Burnett AL, Nehra A, Breau RH, Culkin DJ, Faraday MM, Hakim LS, et al. Erectile Dysfunction: AUA Guideline. Jour-nal of Urology. 2018; 200: 633–641.
 Sanchez E, Pastuszak AW, Khera M. Erectile dysfunction, metabolic syndrome, and cardiovascular risks: facts and contro-versies. Translational Andrology and Urology. 2017; 6: 28–36.
 Teloken PE, Mulhall JP. Impact of phosphodiesterase type 5 in-hibitors on endothelial function. Reviews in Urology. 2008; 10: 26–30.
 Persu C, Cauni V, Gutue S, Albu ES, Jinga V, Geavlete P. Diag-nosis and treatment of erectile dysfunction–a practical up-date. Journal of Medicine and Life. 2009; 2: 394–400.
 Kaya C, Uslu Z, Karaman I. Is endothelial function impaired in erectile dysfunction patients? International Journal of Impo-tence Research. 2006; 18: 55–60.
 Aversa A, Bruzziches R, Francomano D, Natali M, Gareri P, Spera G. Endothelial dysfunction and erectile dysfunction in the aging man. International Journal of Urology. 2010; 17: 38–47.
 Moon KH, Park SY, Kim YW. Obesity and Erectile Dysfunction: from Bench to Clinical Implication. The World Journal of Men’s Health. 2019; 37: 138.
 Chu NV, Edelman SV. Erectile dysfunction and diabetes. Current Diabetes Reports. 2002; 2: 60–66.
 Hatzimouratidis K, Amar E, Eardley I, Giuliano F, Hatzichris-tou D, Montorsi F, et al. Guidelines on Male Sexual Dysfunc-tion: Erectile Dysfunction and Premature Ejaculation. European Urology. 2010; 57: 804–814.
 Mobley DF, Khera M, Baum N. Recent advances in the treatment of erectile dysfunction. Postgraduate Medical Journal. 2017; 93: 679–685.
 Pan MM, Raees A, Kovac JR. Low-Intensity Extracorporeal Shock Wave as a Novel Treatment for Erectile Dysfunction. American Journal of Men’s Health. 2016; 10: 146–148.
 Kałka D, Gebala J, Smoliński R, Rusiecki L, Pilecki W, Zdro-jowy R. Low-energy Shock Wave Therapy—a Novel Treat-ment Option for Erectile Dysfunction in Men with Cardiovascular Disease. Urology. 2017; 109: 19–26.
 Man L, Li G. Low-intensity Extracorporeal Shock Wave Ther-apy for Erectile Dysfunction: a Systematic Review and Me-ta-analysis. Urology. 2018; 119: 97–103.
 Lu Z, Lin G, Reed-Maldonado A, Wang C, Lee YC, Lue TF. Low-intensity Extracorporeal Shock Wave Treatment Im-proves Erectile Function: a Systematic Review and Meta-analysis. Eu-ropean Urology. 2017; 71: 223–233.
 Hatzichristou D. Low-Intensity Extracorporeal Shock Waves Therapy (LI-ESWT) for the treatment of erectile dysfunction: where do we stand? European Urology. 2017; 71: 234–236.
 Lei H, Liu J, Li H, Wang L, Xu Y, Tian W, et al. Low-Intensity Shock Wave Therapy and its Application to Erec-tile Dysfunc-tion. The World Journal of Men’s Health. 2013; 31: 208.
 Rizk PJ, Krieger JR, Kohn TP, Pastuszak AW. Low-Intensity Shockwave Therapy for Erectile Dysfunction. Sexual Medi-cine Reviews. 2018; 6: 624–630.
 Gruenwald I, Appel B, Vardi Y. Low‐Intensity Extracorporeal Shock Wave Therapy—a Novel Effective Treatment for Erec-tile Dysfunction in Severe ED Patients Who Respond Poorly to PDE5 Inhibitor Therapy. The Journal of Sexual Medicine. 2012; 9: 259–264.
 Yamaçake KGR, Carneiro F, Cury J, Lourenço R, Françolin PC, Piovesan AC, et al. Low-intensity shockwave therapy for erec-tile dysfunction in kidney transplant recipients. a prospective, randomized, double blinded, sham-controlled study with evalu-ation by penile Doppler ultrasonography. International Journal of Impotence Research. 2019; 31: 195–203.
 Porst H. Review of the Current Status of Low Intensity Extracor-poreal Shockwave Therapy (Li-ESWT) in Erectile Dys-function (ED), Peyronie’s Disease (PD), and Sexual Rehabilitation after Radical Prostatectomy with Special Focus on Technical Aspects of the Different Marketed ESWT Devices Including Personal Experiences in 350 Patients. Sexual Medicine Reviews. 2021; 9: 93–122.
 Sokolakis I, Hatzichristodoulou G. Clinical studies on low inten-sity extracorporeal shockwave therapy for erectile dys-function: a systematic review and meta-analysis of randomised controlled trials. International Journal of Impotence Research. 2019; 31: 177–194.
 Campbell JD, Milenkovic U, Usta MF, Albersen M, Bivalac-qua TJ. The good, bad, and the ugly of regenerative therapies for erectile dysfunction. Translational Andrology and Urology. 2020; 9: S252–S261.
 Brunckhorst O, Wells L, Teeling F, Muir G, Muneer A, Ahmed K. A systematic review of the long-term efficacy of low-intensity shockwave therapy for vasculogenic erectile dysfunc-tion. International Urology and Nephrology. 2019; 51: 773–781.
 Liu MC, Chang ML, Wang YC, Chen WH, Wu CC, Yeh SD. Re-visiting the Regenerative Therapeutic Advances Towards Erec-tile Dysfunction. Cells. 2020; 9: 1250.
 Chung E, Lee J, Liu CC, Taniguchi H, Zhou HL, Park HJ. Clin-ical Practice Guideline Recommendation on the Use of Low In-tensity Extracorporeal Shock Wave Therapy and Low Intensity Pulsed Ultrasound Shock Wave Therapy to Treat Erectile Dys-function: the Asia-Pacific Society for Sexual Medicine Position Statement. The World Journal of Men’s Health. 2021; 39: 1–8.
 Rompe JD, Kirkpatrick CJ, Küllmer K, Schwitalle M, Krischek O. Dose-related effects of shock waves on rabbit tendo Achillis. The Journal of Bone and Joint Surgery. 1998; 80: 546–552.
 Ortac M, Kucukergin C, Salabas E, Seckin S, Kadioglu A. Effect of low-energy shockwave therapy on angiogenic factors in the penile tissue of diabetic rats. Turkish Journal of Urology. 2017; 43: 130–134.
 Nishida T, Shimokawa H, Oi K, Tatewaki H, Uwatoku T, Abe K, et al. Extracorporeal Cardiac Shock Wave Ther-apy Markedly Ameliorates Ischemia-Induced Myocardial Dysfunction in Pigs in Vivo. Circulation. 2004; 110: 3055–3061.
 Wang CJ, Wang FS, Yang KD, Weng LH, Hsu CC, Huang CS, et al. Shock wave therapy induces neovasculariza-tion at the tendon–bone junction. a study in rabbits. Journal of Orthopaedic Research. 2003; 21: 984–989.
 Hansen LK, Schrøder HD, Lund L, Rajagopal K, Maduri V, Sel-lathurai J. The effect of low intensity shockwave treatment (Li-SWT) on human myoblasts and mouse skeletal muscle. BMC Musculoskeletal Disorders. 2017; 18: 557.
 Wang CJ, Huang HY, Pai CH. Shock wave-enhanced neovascu-larization at the tendon-bone junction: an experiment in dogs. The Journal of Foot and Ankle Surgery. 2002; 41: 16–22.
 Fode M, Hatzichristodoulou G, Serefoglu EC, Verze P, Albersen M. Low-intensity shockwave therapy for erectile dys-function: is the evidence strong enough? Nature Reviews Urology. 2017; 14: 593–606.
 Yahata K, Kanno H, Ozawa H, Yamaya S, Tateda S, Ito K, et al. Low-energy extracorporeal shock wave therapy for promotion of vascular endothelial growth factor expression and angiogen-
esis and improvement of locomotor and sensory func-tions after spinal cord injury. Journal of Neurosurgery. 2016; 25: 745–755.
 Chen LD, Pan FS, Zhou LY, Liu YB, Lv JY, Xu M, et al. Value of flaccid penile ultrasound in screening for arte-riogenic impo-tence: a preliminary prospective study. BMC Medical Imaging. 2018; 18: 40.
 Vipul A. Color Doppler sonography of the flaccid penis: role in evaluation of erectile dysfunction. European Congress of Radi-ology. 2018. Available at: http://epos.myesr.org/poster/ecr2018/ /C-0822 (Accessed: 27 November 2019).
 Kahvecioğlu N, Kurt A, İpek A, Yazicioğlu K, Akbulut Z. Pre-dictive value of cavernosal peak systolic velocity in the flac-cid penis. Advances in Medical Sciences. 2009; 54: 233–238.
 Sen J, Singh R, Airon RK, Godara R. Colour Doppler Sonog-raphy of Flaccid Penis in Evaluation of Erectile Dysfunction. Asian Journal of Surgery. 2007; 30: 122–125.
 Kanda Y. Investigation of the freely available easy-to-use soft-ware ‘EZR’ for medical statistics. Bone Marrow Transplan-tation. 2013; 48: 452–458.
 Hatzimouratidis K, Giuliano F, Moncada I. EAU guide-lines on erectile dysfunction, premature ejaculation, pe-nile curva-ture and priapism (European Association of Urol-ogy, Arnhem, The Netherlands, 2018). 2018. Available at: https://uroweb.org/wp-content/uploads/EAU-Guidelines-on- Male-Sexual-Dysfunction-2018-large-text.pdf (Accessed: 8 February 2020).
 LeRoy TJ, Broderick GA. Doppler Blood Flow Analysis of Erectile Function: who, when, and how. Urologic Clinics of North America. 2011; 38: 147–154.
 Golijanin D, Singer E, Davis R, Bhatt S, Seftel A, Dogra V. Doppler evaluation of erectile dysfunction – Part 2. Interna-tional Journal of Impotence Research. 2007; 19: 43–48.
 Tung SY, Chang YK, Liu SP, Hsieh JT, Chang HC. Correla-tion between penile Doppler ultrasound findings and penile ar-terial insufficiency under percutaneous transluminal angioplasty for patients with erectile dysfunction. European Urology Sup-plements. 2018; 17: e1579.
 Tung SY, Chang YK, Chang HC, Wang TD, Wen-Jeng L, Liu SP, et al. Current cut-off value for peak systolic velocity and resistance index under penile doppler ultrasound not adequate enough for patient with erectile dysfunction. Journal of Urology. 2019; 201: e759–e760.
 Mutnuru PC, Ramanjaneyulu HK, Susarla R, Yarlagadda J, De-vraj R, Palanisamy P. Pharmaco Penile Duplex Ultrasonog-raphy in the Evaluation of Erectile Dysfunction. Journal of Clin-ical and Diagnostic Research. 2017; 11: TC07–TC10.
 Jung DC, Park SY, Lee JY. Penile Doppler ultrasonography re-visited. Ultrasonography. 2018; 37: 16–24.
 Berookhim BM. Doppler Duplex Ultrasonography of the Penis. The Journal of Sexual Medicine. 2016; 13: 726–731.
 Sikka SC, Hellstrom WJG, Brock G, Morales AM. Standardiza-tion of Vascular Assessment of Erectile Dysfunction. The Jour-nal of Sexual Medicine. 2013; 10: 120–129.
 Gatkin M, Sopotov A. 557 Doppler test in penis flaccid state to asses erectile dysfunction severity and shockwave treat-ment outcomes. The Journal of Sexual Medicine. 2018; 15: S331–S332.
 Ferrara N. Vascular Endothelial Growth Factor: Basic Science and Clinical Progress. Endocrine Reviews. 2004; 25: 581–611.
 Sahara M, Sata M, Morita T, Nakajima T, Hirata Y, Na-gai R. A Phosphodiesterase-5 Inhibitor Vardenafil Enhances Angio-genesis through a Protein Kinase G–Dependent Hypoxia-Inducible Factor-1/Vascular Endothelial Growth Factor Path-way. Arterio-sclerosis, Thrombosis, and Vascular Biology. 2010; 30: 1315–1324.
 Cébe Suarez S, Pieren M, Cariolato L, Arn S, Hoffmann U, Bogucki A, et al. A VEGF-A splice variant defective for hep-aran sulfate and neuropilin-1 binding shows attenuated signaling through VEGFR-2. Cellular and Molecular Life Sciences. 2006; 63: 2067–2077.
 Mecollari V, Nieuwenhuis B, Verhaagen J. A perspective on the role of class III semaphorin signaling in central nervous system trauma. Frontiers in Cellular Neuroscience. 2014; 8: 328.
 Capece M, Verze P, Creta M, La Rocca R, Persico F, Spirito L, et al. Efficacy and safety of low-intensity shock-wave therapy plus tadalafil 5 mg once daily in men with type 2 diabetes mellitus and erectile dysfunction: a matched-pair compari-son study. Asian Journal of Andrology. 2020; 22: 379.
 Vardi Y, Appel B, Jacob G, Massarwi O, Gruenwald I. Can Low-Intensity Extracorporeal Shockwave Therapy Improve Erectile Function? A 6-Month Follow-up Pilot Study in Patients with Or-ganic Erectile Dysfunction. European Urology. 2010; 58: 243–248.
 Srini VS, Reddy RK, Shultz T, Denes B. Low intensity extracor-poreal shockwave therapy for erectile dysfunction: a study in an Indian population. The Canadian Journal of Urology. 2015; 22: 7614–7622.
 Clavijo RI, Kohn TP, Kohn JR, Ramasamy R. Effects of Low-Intensity Extracorporeal Shockwave Therapy on Erectile Dys-function: A Systematic Review and Meta-Analysis. The Journal of Sexual Medicine. 2017; 14: 27–35.
Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.
Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.
Directory of Open Access Journals (DOAJ) DOAJ is a unique and extensive index of diverse open access journals from around the world, driven by a growing community, committed to ensuring quality content is freely available online for everyone.
SCImago The SCImago Journal & Country Rank is a publicly available portal that includes the journals and country scientific indicators developed from the information contained in the Scopus® database (Elsevier B.V.)
Publication Forum - JUFO (Federation of Finnish Learned Societies) Publication Forum is a classification of publication channels created by the Finnish scientific community to support the quality assessment of academic research.
Scopus CiteScore 0.7 (2021) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.
Norwegian Register for Scientific Journals, Series and Publishers Search for publication channels (journals, series and publishers) in the Norwegian Register for Scientific Journals, Series and Publishers to see if they are considered as scientific. (https://kanalregister.hkdir.no/publiseringskanaler/Forside).