A Novel Method for Identifying and Treating Erectile Dysfunction
Pharmaceutical sciences- Pharmaceutics
DOI:
https://doi.org/10.22376/ijlpr.2023.13.6.P234-P252Keywords:
Erectile dysfunction, Nanotechnology, penile erection, emerging treatment, management of ED, NPTR test.Abstract
Sexual or erectile dysfunction (ED) is the ineptitude to get or keep a hard penile erection. ED can have a detrimentaleffect on physical and psychological health. This review helps in understanding the detailed etiology of ED and variousapproaches for the management of ED. The occurrence and incidence of erectile dysfunction are on the rise among men.Various other factors greatly impact the progression of ED, including individual general health and physiological conditions suchas psychiatric or psychological problems, diabetes mellitus, genitourinary disease, cardiovascular disease, and chronic diseases.Erectile dysfunction occurs when the release of nitric oxide (NO) triggers the activation of the guanylate cyclase enzyme in thespongiosum and corpora cavernosa, leading to relaxation of the vascular smooth muscle and an increase in cyclic guanosinemonophosphate (cGMP) levels. This physiological process is essential for achieving and maintaining a firm penile erection. Somecommon and advanced methods, such as the physical method, sexual history, laboratory testing, apomorphine test, NPTR test,and color duplex Doppler ultrasound test, are used to diagnose erectile dysfunction. This review also focuses on emergingtreatments that address the medical need for effective ED management. This comprehensive review bridges gaps in the currentliterature, offering superior insights into ED management and improving the quality of life for individuals with ED.
References
Althof SE, McMahon CG, Waldinger MD, Serefoglu EC, Shindel AW, Ganesan Adaikan P, et al. An update of the International Society of Sexual Medicine's guidelines for diagnosing and treating premature ejaculation (PE). J Sex Med. 2014;11(6):1392-422. doi: 10.1111/jsm.12504.
Vlachopoulos C, Jackson G, Stefanadis C, Montorsi P. Erectile dysfunction in the cardiovascular patient. Eur Heart J. 2013;34(27):2034-46. doi: 10.1093/eurheartj/eht112, PMID 23616415.
Cronenwett J, Johnston K. Erectile dysfunction. In: Cronenwett JL, Wayne Johnston K, editors. Rutherford’s vascular surgery. 8th ed. Philadelphia: Saunders; 2014. p. 1208-20.
Liu Q, Zhang Y, Wang J, Li S, Cheng Y, Guo J, et al. Erectile dysfunction and depression: a systematic review and meta-analysis. J Sex Med. 2018 Aug;15(8):1073-82. doi: 10.1016/j.jsxm.2018.05.016, PMID 29960891.
Yuan J, Desouza R, Westney OL, Wang R. Insights of priapism mechanism and rationale treatment for recurrent priapism. Asian J Androl. 2008;10(1):88-101. doi: 10.1111/j.1745-7262.2008.00314.x, PMID 18087648.
Ayta IA, McKinlay JB, Krane RJ. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int. 1999;84(1):50-6. doi: 10.1046/j.1464-410x.1999.00142.x, PMID 10444124.
De Boer BJ, Bots ML, Lycklama A Nijeholt AA, Moors JPC, Pieters HM, Verheij TJM. Erectile dysfunction in primary care: prevalence and patient characteristics. The ENIGMA study. Int J Impot Res. 2004;16(4):358-64. doi: 10.1038/sj.ijir.3901155, PMID 14961062.
Gebremedhin HT, Mezgebo HM, Geberhiwot GT, Gebru TT, Tesfamichael YA, Ygzaw HB et al. Erectile dysfunction and its associated factors among the male population in Adigrat Town, Tigrai Region, Ethiopia: A cross-sectional study. PLOS ONE. 2021;16(3):e0242335. doi: 10.1371/journal.pone.0242335, PMID 33740010.
Hellstrom WJG, Bivalacqua TJ. Peyronie’s disease: etiology, medical, and surgical therapy. J Androl. 2000;21(3):347-54. doi: 10.1002/j.1939-4640.2000.tb03415.x, PMID 10819440.
Rosen RC, Cappelleri JC, Gendrano N. The International Index of Erectile Function (IIEF): A state-of-the-science review. Int J Impot Res. 2002;14(4):226-44. doi: 10.1038/sj.ijir.3900857, PMID 12152111.
Moreira ED, Bestane WJ, Bartolo EB, Fittipaldi JA. Prevalence and determinants of erectile dysfunction in Santos, southeastern Brazil. Sao Paulo Med J. 2002;120(2):49-54. doi: 10.1590/s1516-31802002000200005, PMID 11994773.
Corona G, Lee DM, Forti G, O’Connor DB, Maggi M, O’Neill TW. Age-related changes in general and sexual health in middle-aged and older men: results from the European Male Ageing Study (EMAS). J Sex Med. 2010;7(4 Pt 1):1362-80. doi: 10.1111/j.1743-6109.2009.01626.x.
Hamada A, Esteves SC, Nizza M, Agarwal A. Unexplained male infertility: diagnosis and management. Int Braz J Urol. 2012;38(5):576-94. doi: 10.1590/S1677-55382012000500002, PMID 23131516.
Lu Z, Lin G, Reed-Maldonado A, Wang C, Lee YC, Lue TF. Low-intensity extracorporeal shock wave treatment improves erectile function: A systematic review and meta-analysis. Eur Urol. 2017;71(2):223-33. doi: 10.1016/j.eururo.2016.05.050.
von Keitz A, Rajfer J, Segal S, Murphy A, Denne J, Costigan T et al. A multicenter, randomized, double-blind, crossover study to evaluate patient preference between tadalafil and sildenafil. Eur Urol. 2004;45(4):499-507; discussion 507. doi: 10.1016/j.eururo.2003.11.030, PMID 15041116.
Manchanda A, Soran O. Enhanced external counterpulsation and future directions. Step beyond medical management for patients with angina and heart failure. J Am Coll Cardiol. 2007;50(16):1523-31. doi: 10.1016/j.jacc.2007.07.024, PMID 17936150.
Hull EM, Eaton RC, Markowski VP, Moses J, Lumley LA, Loucks JA. Opposite influence of medial preoptic D1 and D2 receptors on genital reflexes: implications for copulation. Life Sci. 1992;51(22):1705-13. doi: 10.1016/0024-3205(92)90299-5, PMID 1359367.
Melis MR, Stancampiano R, Gessa GL, Argiolas A. Prevention by morphine of apomorphine- and oxytocin-induced penile erection and yawning: site of action in the brain. Neuropsychopharmacology. 1992;6(1):17-21. doi: 10.1016/0893-133X(92)90003-3, PMID 1315136.
de Groat WC, Booth A. Neural control of penile erection. In: Maggi CA, editor. The autonomic nervous system. London: Harwood; 1993. p. 465-513. ISBN: 978-3718659452.
Gelez H, Poirier S, Facchinetti P, Allers KA, Wayman C, Alexandre L, et al. Neuroanatomical evidence for a role of central melanocortin-4 receptors and oxytocin in the efferent control of the rodent clitoris and vagina. J Sex Med. 2010;7(6):2056-67. doi: 10.1111/j.1743-6109.2010.01760.x, PMID 20345736.
Van der Ploeg LH, Martin WJ, Howard AD, Nargund RP, Austin CP, Guan X, et al. A role for the melanocortin 4 receptor in sexual function. Proc Natl Acad Sci U S A. 2002;99(17):11381-6. doi: 10.1073/pnas.172378699, PMID 12172010.
Dean RC, Lue TF. Physiology of penile erection and pathophysiology of erectile dysfunction. Urol Clin North Am. 2005;32(4):379-95, v. doi: 10.1016/j.ucl.2005.08.007, PMID 16291031.
Lue TF. Physiology of penile erection and pathophysiology of erectile dysfunction. In: Wein AJ, Kavoussi LR, Novick AC, Partin AW, et al., editors. Campbell-Walsh urology. 10th ed. Philadelphia: W B Saunders Company; 2012. p. 688-720. doi: 10.1016/b978-1-4160-6911-9.00020-2.
Dai Y, Zhang Y, Phatarpekar P, Mi T, Zhang H, Blackburn MR, et al. Adenosine signaling, priapism, and novel therapies. J Sex Med. 2009;6;Suppl 3:292-301. doi: 10.1111/j.1743-6109.2008.01187.x, PMID 19267852.
Johnson DA, Akamine P, Radzio-Andzelm E, Madhusudan M, Taylor SS. Dynamics of cAMP-dependent protein kinase. Chem Rev. 2001;101(8):2243-70. doi: 10.1021/cr000226k, PMID 11749372.
Andersson KE, Wagner G. Physiology of penile erection. Physiol Rev. 1995;75(1):191-236. doi: 10.1152/physrev.1995.75.1.191, PMID 7831397.
Simonsen U, Prieto D, Hernández M, Sáenz de Tejada I, García-Sacristán A. Adrenoceptor-mediated regulation of the contractility in horse penile resistance arteries. J Vasc Res. 1997;34(2):90-102. doi: 10.1159/000159206, PMID 9167641.
Rees RW, Ziessen T, Ralph DJ, Kell P, Moncada S, Cellek S. Human and rabbit cavernosal smooth muscle cells express Rho-kinase. Int J Impot Res. 2002;14(1):1-7. doi: 10.1038/sj.ijir.3900814, PMID 11896471.
Ito M, Nakano T, Erdodi F, Hartshorne DJ. Myosin phosphatase: structure, regulation, and function. Mol Cell Biochem. 2004;259(1-2):197-209. doi: 10.1023/b:mcbi.0000021373.14288.00, PMID 15124925.
Hamid SA, Bower HS, Baxter GF. Rho kinase activation plays a major role as a mediator of irreversible injury in reperfused myocardium. Am J Physiol Heart Circ Physiol. 2007;292(6):H2598-606. doi: 10.1152/ajpheart.01393.2006, PMID 17220176.
Large WA. Receptor-operated Ca2(+)-permeable nonselective cation channels in vascular smooth muscle: a physiologic perspective. J Cardiovasc Electrophysiol. 2002;13(5):493-501. doi: 10.1046/j.1540-8167.2002.00493.x, PMID 12030534.
Bivalacqua TJ, Hellstrom WJ. Potential application of gene therapy for the treatment of erectile dysfunction. J Androl. 2001;22(2):183-90. doi: 10.1002/j.1939-4640.2001.tb02296.x, PMID 11229791.
Melman A, Bar-Chama N, McCullough A, Davies K, Christ G. hMaxi-K gene transfer in males with erectile dysfunction: results of the first human trial. Hum Gene Ther. 2006;17(12):1165-76. doi: 10.1089/hum.2006.17.1165, PMID 17134370.
Lu Z, Lin G, Reed-Maldonado A, Wang C, Lee YC, Lue TF. Low-intensity extracorporeal shock wave treatment improves erectile function: A systematic review and meta-analysis. Eur Urol. 2017;71(2):223-33. doi: 10.1016/j.eururo.2016.05.050.
Nurnberg HG, Hensley PL, Gelenberg AJ, Fava M, Lauriello J, Paine S. Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial. JAMA. 2003;289(1):56-64. doi: 10.1001/jama.289.1.56, PMID 12503977.
Huffman LB, Hartenbach EM, Carter J, Rash JK, Kushner DM. Maintaining sexual health throughout gynecologic cancer survivorship: A comprehensive review and clinical guide. Gynecol Oncol. 2016;140(2):359-68. doi: 10.1016/j.ygyno.2015.11.010.
De Leonardis F, Colalillo G, Finazzi Agrò E, Miano R, Fuschi A, Asimakopoulos AD. Endothelial dysfunction, erectile deficit, and cardiovascular disease: an overview of the pathogenetic links. Biomedicines. 2022 Aug;10(8):1848. doi: 10.3390/biomedicines10081848, PMID 36009395.
Yerke AF, Mitchell V. Am I Man Enough Yet? A comparison of the body transition, self-labeling, and sexual orientation of two cohorts of female-to-male transsexuals. Int J Transgend. 2011;13(2):64-76. doi: 10.1080/15532739.2011.622125.
Andersson KE, Wagner G. Physiology of penile erection. Physiol Rev. 1995;75(1):191-236. doi: 10.1152/physrev.1995.75.1.191, PMID 7831397.
Kaya E, Sikka SC, Gur S. A comprehensive review of metabolic syndrome affecting erectile dysfunction. J Sex Med. 2015;12(4):856-75. doi: 10.1111/jsm.12828, PMID 25675988.
Esposito K, Giugliano F, Di Palo C, Giugliano G, Marfella R, D’Andrea F, et al. Effect of lifestyle changes on erectile dysfunction in obese men: a randomized controlled trial. JAMA. 2004;291(24):2978-84. doi: 10.1001/jama.291.24.2978, PMID 15213209.
Chew KK, Stuckey BG, Earle CM, Jamrozik K. Male erectile dysfunction: its prevalence in Western Australia and associated sociodemographic factors. J Sex Med. 2007;4(1):17-23. doi: 10.1111/j.1743-6109.2006.00333.x.
Kocjancic E, Iacovelli V. Penile prostheses. Clin Plast Surg. 2018;45(3):407-14. doi: 10.1016/j.cps.2018.03.012.
Dewitte M, Bettocchi C, Carvalho J, Corona G, Flink I, Limoncin E, et al. A psychosocial approach to erectile dysfunction: position statements from the European society of sexual medicine (ESSM). Sex Med. 2021;9(6):100434. doi: 10.1016/j.esxm.2021.100434, PMID 34626919.
Deforge D, Blackmer J, Garritty C, Yazdi F. A systematic review of the association between erectile dysfunction and cardiovascular disease. Can J Cardiol. 2016;32(4):492-8. doi: 10.1016/j.cjca.2015.07.755.
Tetreault LA, Singh A, Gholami F, Fehlings MG. Pathophysiology of erectile dysfunction following spinal cord injury. Prog Neurobiol. 2020;186:101732. doi: 10.1016/j.pneurobio.2019.101732.
Kim YJ, Lee DH, Cho ST, Kim KT. Association between acute ischemic stroke and erectile dysfunction: a population-based cohort study. J Clin Med. 2019;8(9):1349. doi: 10.3390/jcm8091349.
Silva TP, Giorelli G, Giometti IC, et al. The relationship between testosterone deficiency and erectile dysfunction in Parkinson’s disease. Aging Male. 2021;24(1):46-52. doi: 10.1080/13685538.2019.1692662.
Sakakibara R, Tateno F, Kishi M, Tsuyusaki Y, Terada H, Inaoka T. Autonomic dysfunction in multiple sclerosis: measurement and pathophysiology. Clin Auton Res. 2019;29(1):31-41. doi: 10.1007/s10286-018-0545-y.
Jha R, Sharma D, Das CJ, Sharma P, Gupta AK. Lumbosacral disc disease and erectile dysfunction: a review of possible etiologies and implications for evaluation and management. Asian J Neurosurg. 2019;14(3):730-6. doi: 10.4103/and.AJNS_5_19.
Rosenbaum TY, Owens JK. Erectile dysfunction in neurological disorders. Sex Med Rev. 2020;8(2):207-16. doi: 10.1016/j.sxmr.2019.07.001.
Khanna NN, Maindarkar M, Saxena A, Ahluwalia P, Paul S, Srivastava SK et al. Cardiovascular/stroke risk assessment in patients with erectile dysfunction—a role of carotid wall arterial imaging and plaque tissue characterization using artificial intelligence paradigm: a narrative review. Diagnostics (Basel). 2022;12(5):1249. doi: 10.3390/diagnostics12051249, PMID 35626404.
de Oliveira AA, Nunes KP. Hypertension and erectile dysfunction: breaking down the challenges. Am J Hypertens. 2021;34(2):134-42. doi: 10.1093/ajh/hpaa143, PMID 32866225.
Chen L, Shi GR, Huang DD, Li Y, Ma CC, Shi M, et al. Male sexual dysfunction: a review of literature on its pathological mechanisms, potential risk factors, and herbal drug intervention. Biomed Pharmacother. 2019;112:108585. doi: 10.1016/j.biopha.2019.01.046, PMID 30798136.
Sopko NA, Hannan JL, Bivalacqua TJ. Understanding and targeting the Rho kinase pathway in erectile dysfunction. Nat Rev Urol. 2014;11(11):622-8. doi: 10.1038/nrurol.2014.278, PMID 25311680.
Magheli A, Burnett AL. Erectile dysfunction following prostatectomy: prevention and treatment. Nat Rev Urol. 2009;6(8):415-27. doi: 10.1038/nrurol.2009.126, PMID 19657376.
Traish AM, Munarriz R, O’Connell L, Choi S, Kim SW, Kim NN, et al. Effects of medical or surgical castration on erectile function in an animal model. J Androl. 2003;24(3):381-7. doi: 10.1002/j.1939-4640.2003.tb02686.x, PMID 12721214.
Mulhall JP, Morgentaler A. Penile rehabilitation should become the norm for radical prostatectomy patients. J Sex Med. 2007;4(3):538-43. doi: 10.1111/j.1743-6109.2007.00486.x, PMID 17498093.
Gratzke C, Angulo J, Chitaley K, Dai YT, Kim NN, Paick JS, et al. Anatomy, physiology, and pathophysiology of erectile dysfunction. J Sex Med. 2010;7(1 Pt 2):445-75. doi: 10.1111/j.1743-6109.2009.01624.x, PMID 20092448.
Vardi Y. Microvascular complications in diabetic erectile dysfunction: do we need other alternatives? Diabetes Care. 2009;32;Suppl 2:S420-2. doi: 10.2337/dc09-S351, PMID 19875592.
Araujo AB, Travison TG, Ganz P, Chiu GR, Kupelian V, Rosen RC, et al. Erectile dysfunction and mortality. J Sex Med. 2009;6(9):2445-54. doi: 10.1111/j.1743-6109.2009.01354.x, PMID 19538544.
Lue TF. Erectile dysfunction. N Engl J Med. 2000;342(24):1802-13. doi: 10.1056/NEJM200006153422407, PMID 10853004.
Andersson K-E, Nehra A, Lue T, Burnett A, Goldstein I, Morales A. Erectile physiological and pathophysiological pathways involved in erectile dysfunction. J Urol. 2003;170(2 Pt 2):S6-13; discussion S13. doi: 10.1097/01.ju.0000077119.44445.a7.
Gongora Castillo C, Alvarez Gomez de Segura I, Bonet Furgeri H, de Miguel del Campo E. Impotence of arterial origin: experimental models and assessment of sexual behavior in rats. J Urol (Paris). 1993;99(3):122-6. PMID 7745268.
Jackson G, Rosen RC, Kloner RA, Kostis JB. The second Princeton consensus on sexual dysfunction and cardiac risk: new guidelines for sexual medicine. J Sex Med. 2006;3(1):28-36; discussion 36. doi: 10.1111/j.1743-6109.2005.00196.x, PMID 16409215.
Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994;151(1):54-61. doi: 10.1016/s0022-5347(17)34871-1, PMID 8254833.
Malavige LS, Levy JC. Erectile dysfunction in diabetes mellitus. J Sex Med. 2009;6(5):1232-47. doi: 10.1111/j.1743-6109.2008.01168.x, PMID 19210706.
Broderick GA, Kadioglu A, Bivalacqua TJ, Ghanem H, Nehra A, Shamloul R. Priapism: pathogenesis, epidemiology, and management. J Sex Med. 2010;7(1 Pt 2):476-500. doi: 10.1111/j.1743-6109.2009.01625.x, PMID 20092449.
Spycher MA, Hauri D. The ultrastructure of the erectile tissue in priapism. J Urol. 1986;135(1):142-7. doi: 10.1016/s0022-5347(17)45549-2, PMID 3941454.
Rother RP, Bell L, Hillmen P, Gladwin MT. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA. 2005;293(13):1653-62. doi: 10.1001/jama.293.13.1653, PMID 15811985.
Slag MF, Morley JE, Elson MK, Trence DL, Nelson CJ, Nelson AE, et al. Impotence in medical clinic outpatients. JAMA. 1983;249(13):1736-40. doi: 10.1001/jama.1983.03330370050025, PMID 6827762.
Chang SW, Fine R, Siegel D, Chesney M, Black D, Hulley SB. The impact of diuretic therapy on reported sexual function. Arch Intern Med. 1991;151(12):2402-8. doi: 10.1001/archinte.1991.00400120064012, PMID 1746997.
Fogari R, Zoppi A. Effects of antihypertensive therapy on sexual activity in hypertensive men. Curr Hypertens Rep. 2002;4(3):202-10. doi: 10.1007/s11906-002-0008-3, PMID 12003702.
Loriaux DL, Menard R, Taylor A, Pita JC, Santen R. Spironolactone and endocrine dysfunction. Ann Intern Med. 1976;85(5):630-6. doi: 10.7326/0003-4819-85-5-630, PMID 984618.
Papatsoris AG, Korantzopoulos PG. Hypertension, antihypertensive therapy, and erectile dysfunction. Angiology. 2006;57(1):47-52. doi: 10.1177/000331970605700107, PMID 16444456.
Kolodny RC. Effects of alpha-methyldopa on male sexual function. Sex Disabil. 1978;1(3):223-8. doi: 10.1007/BF01101329.
Newman RJ, Salerno HR [letter]. Letter: sexual dysfunction due to methyldopa. Br Med J. 1974;4(5936):106. doi: 10.1136/bmj.4.5936.106-b, PMID 4414389.
Bansal S. Sexual dysfunction in hypertensive men: a critical review of the literature. Hypertension. 1988;12(1):1-10. doi: 10.1161/01.HYP.12.1.1, PMID 3294176.
Oster JR, Epstein M. Use of centrally acting sympatholytic agents in managing hypertension. Arch Intern Med. 1991;151(8):1638-44. doi: 10.1001/archinte.1991.00400080022004, PMID 1872668.
Goldstein I, Krane RJ. Drug-induced sexual dysfunction. World J Urol. 1983;1(4):239-43. doi: 10.1007/BF00326809.
Shader RI, Elkins R. The effects of antianxiety and antipsychotic drugs and sexual behavior. Mod Probl Pharmacopsychiatry. 1980;15:91-110. doi: 10.1159/000402338, PMID 6106892.
Wolfe MM. Impotence on cimetidine treatment. N Engl J Med. 1979;300(2):94. doi: 10.1056/NEJM197901113000219, PMID 758590.
Wessells H, Levine N, Hadley ME, Dorr R, Hruby V. Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II. Int J Impot Res. 2000;12;Suppl 4:S74-9. doi: 10.1038/sj.ijir.3900582, PMID 11035391.
Diamond LE, Earle DC, Rosen RC, Willett MS, Molinoff PB. Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties, and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction. Int J Impot Res. 2004;16(1):51-9. doi: 10.1038/sj.ijir.3901139, PMID 14963471.
Hellstrom W, Gittelman M, Zinner N, et al. Randomized, double-blind, placebo-controlled, at-home study to evaluate the efficacy and safety of intranasal Bremelanotide in men with erectile dysfunction with and without diabetes mellitus [abstract]. In: Proceedings of the 9th congress of the European Society for Sexual Medicine; Vienna, Austria; 2006. p. 117.
Safarinejad MR, Hosseini SY. Salvage of sildenafil failures with Bremelanotide: a randomized, double-blind, placebo-controlled study. J Urol. 2008;179(3):1066-71. doi: 10.1016/j.juro.2007.10.063, PMID 18206919.
Diamond LE, Earle DC, Garcia WD, Spana C. Co-administration of low doses of intranasal PT-141, a melanocortin receptor agonist, and sildenafil to men with erectile dysfunction results in an enhanced erectile response. Urology. 2005;65(4):755-9. doi: 10.1016/j.urology.2004.10.060, PMID 15833522.
Cowart M, Latshaw SP, Bhatia P, Daanen JF, Rohde J, Nelson SL, et al. Discovery of 2-(4-pyridin-2-ylpiperazin-1-ylmethyl)-1H-benzimidazole (ABT-724), a dopaminergic agent with a novel mode of action for the potential treatment of erectile dysfunction. J Med Chem. 2004;47(15):3853-64. doi: 10.1021/jm030505a, PMID 15239663.
Brioni JD, Moreland RB, Cowart M, Hsieh GC, Stewart AO, Hedlund P, et al. Activation of dopamine D4 receptors by ABT-724 induces penile erection in rats. Proc Natl Acad Sci U S A. 2004;101(17):6758-63. doi: 10.1073/pnas.0308292101, PMID 15087502.
Patel MV, Kolasa T, Mortell K, Matulenko MA, Hakeem AA, Rohde JJ, et al. Discovery of 3-methyl-N-(1-oxy-3',4',5',6'-tetrahydro-2'H-[2,4'-bipyridine]-1'-ylmethyl)benzamide (ABT-670), an orally bioavailable dopamine D4 agonist for the treatment of erectile dysfunction. J Med Chem. 2006;49(25):7450-65. doi: 10.1021/jm060662k, PMID 17149874.
Chan JS, Kim DJ, Ahn CH, Oosting RS, Olivier B. Clavulanic acid stimulates sexual behavior in male rats. Eur J Pharmacol. 2009;609(1-3):69-73. doi: 10.1016/j.ejphar.2009.03.009, PMID 19285063.
Rexahn pharmaceuticals, Inc. efficacy study of RX-10100 to treat erectile dysfunction (ED). ClinicalTrials.gov. National Library of Medicine. Bethesda; 2009.
Oudot A, Behr-Roussel D, Poirier S, Sandner P, Bernabé J, Alexandre L, et al. Combination of BAY 60-4552 and vardenafil exerts pro-erectile facilitator effects in rats with cavernous nerve injury: a proof of concept study for the treatment of phosphodiesterase type 5 inhibitor failure. Eur Urol. 2011;60(5):1020-6. doi: 10.1016/j.eururo.2011.07.052, PMID 21839578.
Albersen M, Linsen L, Tinel H, Sandner P, Van Renterghem K. Synergistic effects of BAY 60-4552 and vardenafil on relaxation of corpus cavernosum tissue of patients with erectile dysfunction and clinical phosphodiesterase type 5 inhibitor failure. J Sex Med. 2013;10(5):1268-77. doi: 10.1111/jsm.12095, PMID 23421435.
Bayer Healthcare AG. A prospective, randomized, double-blind, double-dummy, placebo and active-controlled, multicenter study assessing the efficacy and safety of the combination BAY 60 4552/ vardenafil compared to vardenafil (20 mg) for the treatment of erectile dysfunction not sufficiently responsive to standard therapy with PDE5 inhibitors. ClinicalTrials.gov. National Library of Medicine. Bethesda; 2014.
Buyukafsar K, I. Effects of the Rho-kinase inhibitors, Y-27632, and fasudil, on the corpus cavernosum from diabetic mice. Eur J Pharmacol. 2003;472(3):235-8. doi: 10.1016/s0014-2999(03)01838-3.
Lasker GF, Maley JH, Kadowitz PJ. A review of the pathophysiology and novel treatments for erectile dysfunction. Adv Pharmacol Sci. 2010;2010:1-10. doi: 10.1155/2010/730861.
Guagnini F, Ferazzini M, Grasso M, Blanco S, Croci T. Erectile properties of the Rho-kinase inhibitor SAR407899 in diabetic animals and human isolated corpora cavernosa. J Transl Med. 2012;10:59. doi: 10.1186/1479-5876-10-59, PMID 22444253.
Sanofi. Avenis. Randomized, double-blind, placebo, and active-controlled study of the activity of SAR407899 single-dose on the ability to increase the duration of penile rigidity, under experimental conditions, in patients with mild to moderate erectile dysfunction. National Library of Medicine. ClinicalTrials.gov. Bethesda; 2009.
Bentzen BH, Olesen SP, Rønn LC, Grunnet M. BK channel activators and their therapeutic perspectives. Front Physiol. 2014;5:389. doi: 10.3389/fphys.2014.00389, PMID 25346695.
Kun A, Matchkov VV, Stankevicius E, Nardi A, Hughes AD, Kirkeby HJ, et al. NS11021, a novel opener of large-conductance Ca(2+)-activated K(+) channels, enhance erectile responses in rats. Br J Pharmacol. 2009;158(6):1465-76. doi: 10.1111/j.1476-5381.2009.00404.x, PMID 19845682.
Király I, Pataricza J, Bajory Z, Simonsen U, Varro A, Papp JG, et al. Involvement of large-conductance Ca(2+)-activated K(+) channels in both nitric oxide and endothelium-derived hyperpolarization-type relaxation in human penile small arteries. Basic Clin Pharmacol Toxicol. 2013;113(1):19-24. doi: 10.1111/bcpt.12059, PMID 23414060.
Ghofrani HA, Osterloh IH, Grimminger F. Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond. Nat Rev Drug Discov. 2006 Aug;5(8):689-702. doi: 10.1038/nrd2030, PMID 16883306.
Park B, Jeon BG, Kim HJ, Kim JJ. The association between hyperlipidemia and erectile dysfunction: a systematic review and meta-analysis. J Mens Health. 2019;15(3):e33-43. doi: 10.1016/j.jomh.2019.04.001.
Kalyvianakis D, Mykoniatis I, Pyrgidis N, Kapoteli P, Zilotis F, Fournaraki A et al. The effect of low-intensity shock wave therapy on moderate erectile dysfunction: a double-blind, randomized, sham-controlled clinical trial. J Urol. 2022;208(2):388-95. doi: 10.1097/JU.0000000000002684, PMID 35830338.
Cilio S, Pozzi E, Fallara G, Belladelli F, Corsini C, d’Arma A et al. Premature ejaculation among men with erectile dysfunction—findings from a real-life cross-sectional study. Int J Impot Res. 2022:1-6. doi: 10.1038/s41443-022-00601-4, PMID 35915329.
McMahon CG. Current diagnosis and management of erectile dysfunction. Med J Aust. 2019;210(10):469-76. doi: 10.5694/mja2.50167, PMID 31099420.
Carson CC, Osbon JH, Bennett NE. Ambicor two-piece inflatable penile prosthesis: background and contemporary outcomes. Sex Med Rev. 2018;6:319-27. doi: 10.1016/j.sxmr.2017.07.010.
Gray RE, Klotz LH. Restoring sexual function in prostate cancer patients: an innovative approach. Can J Urol. 2004;11(3):2285-9. doi: 10.1002/j.1939-4640.2004.tb02991.x, PMID 15287995.
Liu J, Zhou F, Yang Y, Zhao J, Zhao Z, Tian H. A novel method to assess rat erectile function using a new device for continuous measurement of intracavernous pressure: the apomorphine test combined with the sustained erection test. Int J Impot Res. 2015;27(3):89-94. doi: 10.1038/ijir.2015.3.
Salvio G, Ciarloni A, Cordoni S, Cutini M, Delli Muti ND, Finocchi F, et al. Homocysteine levels correlate with velocimetric parameters in patients with erectile dysfunction undergoing penile duplex ultrasound. Andrology. 2022;10(4):733-9. doi: 10.1111/andr.13169, PMID 35224883.
Wang M, Dai Y, Jiang H, Sansone A, Jannini EA, Zhang X. Application of dual-energy CT angiography in the diagnosis of arterial erectile dysfunction: new scanning technology, new scanning area. Aging Male. 2022;25(1):257-65. doi: 10.1080/13685538.2022.2121815, PMID 36102620.
Xu W, Jiang H, Liu J, Li HN-C. Non-coding RNAs: a new dawn for diabetes mellitus induced erectile dysfunction. Front Mol Biosci. 2022;9:888624. doi: 10.3389/fmolb.2022.888624, PMID 35813828.
Pedraza AM, Pandav K, Menon M, Khera M, Wagaskar V, Dovey Z, et al. Current strategies to improve erectile function in patients undergoing radical prostatectomy-postoperative scenario. Urol Oncol. 2022;40(3):87-94. doi: 10.1016/j.urolonc.2021.12.002, PMID 35012822.
Yang B, Hong Z, Luse DC, Han Y, Sun G, Feng Y, et al. The diagnostic role of neurophysiological tests for premature ejaculation: a prospective multicenter study. J Urol. 2022;207(1):172-82. doi: 10.1097/JU.0000000000002198, PMID 34455861.
Popov SV, Orlov IN, Grin’ YA, Malevich SM, Gul’ko AM, Topuzo TM et al. Erectile dysfunction: new technologies and approaches in diagnostics and treatment. Vestn Urol. 2020;8(2):78-92. doi: 10.21886/2308-6424-2020-8-2-78-92.
Itzhak I, Cohen S, Fishman S, Fishman P. A3 adenosine receptor allosteric modulator CF602 reverses erectile dysfunction in a diabetic rat model. Andrologia. 2022;54(9):e14498. doi: 10.1111/and.14498, PMID 35732294.
Hatzimouratidis K, Amar E, Eardley I, et al. Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. European Association of Urology; 2010. Available from: https://uroweb.org/wp-content/uploads/EAU-Guidelines-Male-Sexual-Dysfunction-2010.pdf.
Nehra A, Jackson G, Miner M, Billups KL, Burnett AL, Buvat J, et al. The Princeton III consensus recommendations for the management of erectile dysfunction and cardiovascular disease. Mayo Clin Proc. 2012;87(8):766-78. doi: 10.1016/j.mayocp.2012.06.015, PMID 22862865.
Yang R, Liu C, Li Q, Wang W, Wu B, Chen A, et al. Artificial intelligence-based identification of the functional role of hirudin in diabetic erectile dysfunction treatment. Pharmacol Res. 2021;163:105244. doi: 10.1016/j.phrs.2020.105244, PMID 33053440.
Sun T, Xu W, Wang J, Song J, Wang T, Wang S, et al. Paeonol ameliorates diabetic erectile dysfunction by inhibiting the HMGB1/RAGE/NF-kB pathway. Andrology. 2022;11(2):344-57. doi: 10.1111/andr.13203.
Defeudis G, Mazzilli R, Tenuta M, Rossini G, Zamponi V, Olana S, et al. Erectile dysfunction and diabetes: a melting pot of circumstances and treatments. Diabetes Metab Res Rev. 2022;38(2):e3494. doi: 10.1002/dmrr.3494, PMID 34514697.
Chen X, et al. Panax ginseng in randomized controlled trials: a systematic review. Phytother Res. 2017;31(4):531-8.
Shindel AW, Xin ZC, Lin G, Fandel TM, Huang YC, Banie L, et al. Erectogenic and neurotrophic effects of icariin, a purified extract of horny goat weed (Epimedium spp.) in vitro and in vivo. J Sex Med. 2010;7(4 Pt 1):1518-28. doi: 10.1111/j.1743-6109.2009.01699.x, PMID 20141584.
Ernst E, Pittler MH. Yohimbine for erectile dysfunction: a systematic review and meta-analysis of randomized clinical trials. J Urol. 1998;159(2):433-6. doi: 10.1016/s0022-5347(01)63942-9, PMID 9649257.
Neychev VK, Mitev VI. The aphrodisiac herb Tribulus terrestris does not influence androgen production in young men. J Ethnopharmacol. 2005;101(1-3):319-23. doi: 10.1016/j.jep.2005.05.028.
Cohen AJ, Bartlik B. Ginkgo biloba for antidepressant-induced sexual dysfunction. J Sex Marital Ther. 1998;24(2):139-43. doi: 10.1080/00926239808404927, PMID 9611693.
Salvio G, Ciarloni A, Cordoni S, Cutini M, Delli Muti ND, Finocchi F, et al. Homocysteine levels correlate with velocimetric parameters in patients with erectile dysfunction undergoing penile duplex ultrasound. Andrology. 2022;10(4):733-9. doi: 10.1111/andr.13169, PMID 35224883.
Sultana A, Grice P, Vukina J, Pearce I, Modgil V. Indications and characteristics of penile traction and vacuum erection devices. Nat Rev Urol. 2022;19(2):84-100. doi: 10.1038/s41585-021-00532-7, PMID 34764451.
Rho BY, Kim SH, Ryu JK, Kang DH, Kim JW, Chung DY. Efficacy of low-intensity extracorporeal shock wave treatment in erectile dysfunction following radical prostatectomy: A systematic review and meta-analysis. J Clin Med. 2022;11(10):2775. doi: 10.3390/jcm11102775, PMID 35628901.
Hoyland K, Vasdev N, Adshead J. The use of vacuum erection devices in erectile dysfunction after radical prostatectomy. Rev Urol. 2013;15(2):67-71. PMID 24082845, PMCID PMC3784970.
Gruenwald I, Appel B, Kitrey ND, Vardi Y. Shockwave treatment of erectile dysfunction. Ther Adv Urol. 2013 Apr;5(2):95-9. doi: 10.1177/1756287212470696, PMID 23554844.
Anderson D, Laforge J, Ross MM, Vanlangendonck R, Hasoon J, Viswanath O, et al. Male sexual dysfunction. Health Psychol Res. 2022 Sep 1;10(3):37533. doi: 10.52965/001c.37533, PMID 35999971.
Yao H, Wang X, Liu H, Sun F, Tang G, Bao X et al. Systematic review and meta-analysis of 16 randomized controlled trials of clinical outcomes of low-intensity extracorporeal shock wave therapy in treating erectile dysfunction. Am J Mens Health. 2022 Mar-Apr;16(2):15579883221087532. doi: 10.1177/15579883221087532, PMID 35319291.
Falcone M, Garaffa G, Gillo A, Dente D, Christopher AN, Ralph DJ. Outcomes of inflatable penile prosthesis insertion in 247 patients completing female to male gender reassignment surgery. BJU Int. 2018 Jan;121(1):139-44. doi: 10.1111/bju.14027, PMID 28940910.
Gruenwald I, Appel B, Vardi Y. Low-intensity extracorporeal shock wave therapy – A novel effective treatment for erectile dysfunction in severe ED Patients Who Respond Poorly to PDE5 Inhibitor Therapy. J Sex Med. 2013;10(2):596-603. doi: 10.1111/j.1743-6109.2012.12954.x.
Manfredi C, Castiglione F, Fode M, Lew-Starowicz M, Romero-Otero J, Bettocchi C, et al. News and future perspectives of non-surgical treatments for erectile dysfunction. Int J Impot Res. 2022:1-7. doi: 10.1038/s41443-022-00602-3, PMID 35896717.
Islam MM, Naveen NR, Anitha P, Goudanavar PS, Rao GSNK, Fattepur S, et al. The race to replace PDE5i: recent advances and interventions to treat or manage erectile dysfunction: evidence from patent landscape (2016-2021). J Clin Med. 2022;11(11):3140. doi: 10.3390/jcm11113140, PMID 35683526.
van de Grift TC, Pigot GLS, Boudhan S, Elfering L, Kreukels BPC, Gijs LACL, et al. A longitudinal study of motivations before and psychosexual outcomes after genital gender-confirming surgery in transmen. J Sex Med. 2017;14(12):1621-8. doi: 10.1016/j.jsxm.2017.10.064, PMID 29128275.
Corona G, Maggi M. The role of testosterone in male sexual function. Rev Endocr Metab Disord. 2022;23(6):1159-72. doi: 10.1007/s11154-022-09748-3, PMID 35999483.
Dong C, Xie Z, Wang P, Dong Z. Erectile functional restoration with a genital branch of genitofemoral nerve to pelvic nerve transfer after spinal root transection in rats. Urology. 2021;148:179-84. doi: 10.1016/j.urology.2020.09.029, PMID 33010291.
Wang TD, Lee CK, Chia YC, Tsoi K, Buranakitjaroen P, Chen CH, et al. Hypertension and erectile dysfunction: the role of endovascular therapy in Asia. J Clin Hypertens (Greenwich). 2021;23(3):481-8. doi: 10.1111/jch.14123, PMID 33314715.
Kim S, Cho MC, Cho SY, Chung H, Rajasekaran MR. Novel emerging therapies for erectile dysfunction. World J Mens Health. 2021;39(1):48-64. doi: 10.5534/wjmh.200007, PMID 32202086.
Moncada I, Martinez-Salamanca J, Ruiz-Castañe E, Romero J. Combination therapy for erectile dysfunction involves a PDE5 inhibitor and alprostadil. Int J Impot Res. 2018;30(5):203-8. doi: 10.1038/s41443-018-0046-2, PMID 30050072.
Hamzehnejadi M, Tavakoli MR, Homayouni F, Jahani Z, Rezaei M, Langarizadeh MA, et al. Prostaglandins as a topical therapy for erectile dysfunction: A comprehensive review. Sex Med Rev. 2022;10(4):764-81. doi: 10.1016/j.sxmr.2022.06.004, PMID 36210096.
Wang R. Is there still a role for vacuum erection devices in contemporary sexual medicine? J Sex Med. 2022 May;19(5):682-5. doi: 10.1016/j.jsxm.2022.02.013, PMID 35321831.
Mishra AK, Pandey M, Dewangan HK, Sl N, Sahoo PK. A comprehensive review on liver targeting: emphasis on nanotechnology-based molecular targets and receptors mediated approaches. Curr Drug Targets. 2022;23(15):1381-405. doi: 10.2174/1389450123666220906091432, PMID 36065923.
Yadav D, Semwal BC, Dewangan HK. Grafting, characterization, and enhancement of the therapeutic activity of berberine-loaded pegylated PAMAM dendrimer for cancerous cells. J Biomater Sci Polym Ed. 2022;14:1-14. doi: 10.1080/09205063.2022.2155782.
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