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Diabetic Neuropathy: Clinical Management—Genitourinary Dysfunction in Diabetes

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Diabetic Neuropathy

Part of the book series: Contemporary Diabetes ((CDI))

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Abstract

Diabetic bladder and sexual dysfunction include lower urinary tract symptoms (LUTS), ranging from an overactive to a poorly contractile bladder, erectile dysfunction (ED) in men with orgasmic and ejaculatory dysfunction and in women changes in sexual activity and function. Diabetes involves a two- and threefold increase in risk of LUTS and ED, respectively, with a prevalence of each condition over 50%. In women urinary incontinence is present in up to 39%, with an odds ratio of up to 3.5. In addition to somatic and autonomic neuropathy, abnormalities of detrusor muscle, urothelium, and urethra play a role in bladder dysfunction. Neurogenic, vasculogenic, hormonal, metabolic, drug-induced, and psychological factors can contribute to ED and sexual dysfunction in diabetes. ED has a close relation with cardiovascular risk factors and disease and is considered an early risk biomarker for cardiovascular events. Bladder and sexual dysfunction impact on quality of life and prognosis and often coexist in the same patients.

Assessment of LUTS requires history, questionnaires, a bladder diary, urinalysis, uroflowmetry with post-void residual measurement, and urodynamics only for differential diagnosis or in cases resistant to treatment. A stepwise treatment of LUTS includes antimuscarinics or β-3 agonists as the first-line treatment for detrusor overactivity, followed by tibial nerve stimulation as the second-line, with onabotulinumtoxinA and sacral neuromodulation, and by surgery as the last option. Treatments for underactive bladder include intermittent catheterization, followed by neuromodulation. The diagnostic pathway in patients with ED includes history and physical examination, laboratory testing for metabolic and cardiovascular risk stratification, and diagnosis of hypogonadotropic hypogonadism. Treatment of ED includes PDE5-inhibitors as first-line agents, testosterone replacement in the presence of hypogonadism, and psychological counseling for psychosexual dysfunction. Intraurethral alprostadil suppositories or intracavernosal injections are second-line treatment, as well as external vacuum devices and penile implant prosthesis are the last option. Premature ejaculation has multifactorial pathogenesis, while retrograde ejaculation is mainly related to diabetic neuropathy. A combined pharmacological and psychological approach is required for premature ejaculation and α-agonists and/or tricyclic antidepressants for retrograde ejaculation. Ejaculation dysfunction might impair fertility. Female sexual dysfunction appears mainly driven by social and psychological factors with a possible role of autonomic neuropathy. Treatment requires a multidisciplinary approach and mostly relies on lifestyle intervention and hormone therapy in postmenopausal women.

Barriers to an effective management of diabetic genitourinary dysfunction are the still limited knowledge and clinical research for bladder dysfunction and a widespread underdiagnosis for both bladder and sexual dysfunction. A multidisciplinary approach may favor both diagnosis and effective treatment. New antihyperglycemic drugs might exert a beneficial effect on sexual function through weight control.

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References

  1. Frimodt-Møller C. Diabetic cystopathy: epidemiology and related disorders. Ann Intern Med. 1980;92(2 Pt 2):318–21.

    Article  PubMed  Google Scholar 

  2. Brown JS, Wessells H, Chancellor MB, Howards SS, Stamm WE, Stapleton AE, Steers WD, Van Den Eeden SK, McVary KT. Urologic complications of diabetes. Diabetes Care. 2005;28(1):177–85.

    Article  PubMed  Google Scholar 

  3. Kaplan SA, Te AE, Blaivas JG. Urodynamic findings in patients with diabetic cystopathy. J Urol. 1995;153(2):342–4.

    Article  CAS  PubMed  Google Scholar 

  4. Thüroff JW, Abrams P, Andersson KE, Artibani W, Chapple CR, Drake MJ, Hampel C, Neisius A, Schröder A, Tubaro A. EAU guidelines on urinary incontinence. Eur Urol. 2011;59(3):387–400.

    Article  PubMed  Google Scholar 

  5. Martin S, Vincent A, Taylor AW, Atlantis E, Jenkins A, Januszewski A, O’Loughlin P, Wittert G. Lower urinary tract symptoms, depression, anxiety and systemic inflammatory factors in men: a population-based cohort study. PLoS One. 2015;10(10):e0137903.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Gacci M, Corona G, Sebastianelli A, Serni S, De Nunzio C, Maggi M, Vignozzi L, Novara G, McVary KT, Kaplan SA, Gravas S, Chapple C. Male lower urinary tract symptoms and cardiovascular events: a systematic review and meta-analysis. Eur Urol. 2016;70(5):788–96.

    Article  PubMed  Google Scholar 

  7. Joseph MA, Harlow SD, Wei JT, Sarma AV, Dunn RL, Taylor JM, James SA, Cooney KA, Doerr KM, Montie JE, Schottenfeld D. Risk factors for lower urinary tract symptoms in a population-based sample of African-American men. Am J Epidemiol. 2003;157(10):906–14.

    Article  PubMed  Google Scholar 

  8. Liu RT, Chung MS, Lee WC, Chang SW, Huang ST, Yang KD, Chancellor MB, Chuang YC. Prevalence of overactive bladder and associated risk factors in 1359 patients with type 2 diabetes. Urology. 2011;78(5):1040–5.

    Article  PubMed  Google Scholar 

  9. Pop-Busui R, Hotaling J, Braffett BH, Cleary PA, Dunn RL, Martin CL, Jacobson AM, Wessells H, Sarma AV. DCCT/EDIC Research Group. Cardiovascular autonomic neuropathy, erectile dysfunction and lower urinary tract symptoms in men with type 1 diabetes: findings from the DCCT/EDIC. J Urol. 2015;193(6):2045–51.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Wessells H, Braffett BH, Holt SK, Jacobson AM, Kusek JW, Cowie C, Dunn RL, Sarma AV. DCCT/EDIC Study Group. Burden of urological complications in men and women with long-standing type 1 diabetes in the diabetes control and complications trial/epidemiology of diabetes interventions and complications cohort. Diabetes Care. 2018;41(10):2170–7.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Michel MC, Mehlburger L, Schumacher H, Bressel HU, Goepel M. Effect of diabetes on lower urinary tract symptoms in patients with benign prostatic hyperplasia. J Urol. 2000;163(6):1725–9.

    Article  CAS  PubMed  Google Scholar 

  12. Lee WC, Wu HP, Tai TY, Liu SP, Chen J, Yu HJ. Effects of diabetes on female voiding behavior. J Urol. 2004;172(3):989–92.

    Article  PubMed  Google Scholar 

  13. Yu HJ, Lee WC, Liu SP, Tai TY, Wu HP, Chen J. Unrecognized voiding difficulty in female type 2 diabetic patients in the diabetes clinic: a prospective case-control study. Diabetes Care. 2004;27(4):988–9.

    Article  PubMed  Google Scholar 

  14. Jackson RA, Vittinghoff E, Kanaya AM, Miles TP, Resnick HE, Kritchevsky SB, Simonsick EM, Brown JS, Health, Aging, and Body Composition Study. Urinary incontinence in elderly women: findings from the Health, Aging, and Body Composition Study. Obstet Gynecol. 2004;104(2):301–7.

    Article  CAS  PubMed  Google Scholar 

  15. Lifford KL, Curhan GC, Hu FB, Barbieri RL, Grodstein F. Type 2 diabetes mellitus and risk of developing urinary incontinence. J Am Geriatr Soc. 2005;53(11):1851–7.

    Article  PubMed  Google Scholar 

  16. Danforth KN, Townsend MK, Curhan GC, Resnick NM, Grodstein F. Type 2 diabetes mellitus and risk of stress, urge and mixed urinary incontinence. J Urol. 2009;181(1):193–7.

    Article  PubMed  Google Scholar 

  17. Ebbesen MH, Hannestad YS, Midthjell K, Hunskaar S. Diabetes and urinary incontinence – prevalence data from Norway. Acta Obstet Gynecol Scand. 2007;86(10):1256–62.

    Article  PubMed  Google Scholar 

  18. Phelan S, Kanaya AM, Subak LL, Hogan PE, Espeland MA, Wing RR, Burgio KL, Dilillo V, Gorin AA, West DS, Brown JS. Action for Health in Diabetes (Look AHEAD) Research Group. Prevalence and risk factors for urinary incontinence in overweight and obese diabetic women: action for health in diabetes (Look AHEAD) study. Diabetes Care. 2009;32(8):1391–7.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Appa AA, Brown JS, Creasman J, Van Den Eeden SK, Subak LL, Thom DH, Ferrara A, Huang AJ. Clinical predictors and significance of postvoid residual volume in women with diabetes. Diabetes Res Clin Pract. 2013;101(2):164–9.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Hotaling JM, Sarma AV, Patel DP, Braffett BH, Cleary PA, Feldman E, Herman WH, Martin CL, Jacobson AM, Wessells H, Pop-Busui R. Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Cardiovascular autonomic neuropathy, sexual dysfunction, and urinary incontinence in women with type 1 diabetes. Diabetes Care. 2016;39(9):1587–93.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lenherr SM, Clemens JQ, Braffett BH, Dunn RL, Cleary PA, Kim C, Herman WH, Hotaling JM, Jacobson AM, Brown JS, Wessells H, Sarma AV. DCCT/EDIC Research Group. Glycaemic control and risk of incident urinary incontinence in women with Type 1 diabetes: results from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Diabet Med. 2016;33(11):1528–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wilke T, Boettger B, Berg B, Groth A, Mueller S, Botteman M, Yu S, Fuchs A, Maywald U. Epidemiology of urinary tract infections in type 2 diabetes mellitus patients: an analysis based on a large sample of 456,586 German T2DM patients. J Diabetes Complicat. 2015;29(8):1015–23.

    Article  Google Scholar 

  23. Renko M, Tapanainen P, Tossavainen P, Pokka T, Uhari M. Meta-analysis of the significance of asymptomatic bacteriuria in diabetes. Diabetes Care. 2011;34(1):230–5.

    Article  PubMed  Google Scholar 

  24. Boyko EJ, Fihn SD, Scholes D, Chen CL, Normand EH, Yarbro P. Diabetes and the risk of acute urinary tract infection among postmenopausal women. Diabetes Care. 2002;25(10):1778–83.

    Article  PubMed  Google Scholar 

  25. de Groat WC, Yoshimura N. Anatomy and physiology of the lower urinary tract. Handb Clin Neurol. 2015;130:61–108.

    Article  Google Scholar 

  26. Daneshgari F, Liu G, Birder L, Hanna-Mitchell AT, Chacko S. Diabetic bladder dysfunction: current translational knowledge. J Urol. 2009;182(6 Suppl):S18–26.

    CAS  PubMed Central  Google Scholar 

  27. Esteghamati A, Rashidi A, Nikfallah A, Yousefizadeh A. The association between urodynamic findings and microvascular complications in patients with long-term type 2 diabetes but without voiding symptoms. Diabetes Res Clin Pract. 2007;78(1):42–50.

    Article  PubMed  Google Scholar 

  28. Rapidi CA, Karandreas N, Katsifotis C, Benroubi M, Petropoulou K, Theodorou C. A combined urodynamic and electrophysiological study of diabetic cystopathy. Neurourol Urodyn. 2006;25(1):32–8.

    Article  PubMed  Google Scholar 

  29. Kempler P, Amarenco G, Freeman R, Frontoni S, Horowitz M, Stevens M, Low P, Pop-Busui R, Tahrani AA, Tesfaye S, Várkonyi T, Ziegler D, Valensi P. Toronto Consensus Panel on Diabetic Neuropathy. Management strategies for gastrointestinal, erectile, bladder, and sudomotor dysfunction in patients with diabetes. Diabetes Metab Res Rev. 2011;27(7):665–77.

    Article  CAS  PubMed  Google Scholar 

  30. Van Poppel H, Stessens R, Van Damme B, Carton H, Baert L. Diabetic cystopathy: neuropathological examination of urinary bladder biopsies. Eur Urol. 1988;15(1–2):128–31.

    Article  PubMed  Google Scholar 

  31. Lee WC, Wu HP, Tai TY, Yu HJ, Chiang PH. Investigation of urodynamic characteristics and bladder sensory function in the early stages of diabetic bladder dysfunction in women with type 2 diabetes. J Urol. 2009;181(1):198–203.

    Article  PubMed  Google Scholar 

  32. de Groat WC, Griffiths D, Yoshimura N. Neural control of the lower urinary tract. Compr Physiol. 2015;5(1):327–96.

    PubMed  PubMed Central  Google Scholar 

  33. Yoshimura N, Chancellor MB, Andersson KE, Christ GJ. Recent advances in understanding the biology of diabetes-associated bladder complications and novel therapy. BJU Int. 2005;95(6):733–8.

    Article  PubMed  Google Scholar 

  34. Mossa AH, Galan A, Cammisotto PG, Velasquez Flores M, Shamout S, Barcelona P, Saragovi HU, Campeau L. Antagonism of proNGF or its receptor p75NTR reverses remodelling and improves bladder function in a mouse model of diabetic voiding dysfunction. Diabetologia. 2020;63(9):1932–46.

    Article  CAS  PubMed  Google Scholar 

  35. Daneshgari F, Liu G, Hanna-Mitchell AT. Path of translational discovery of urological complications of obesity and diabetes. Am J Physiol Ren Physiol. 2017;312(5):F887–96.

    Article  CAS  Google Scholar 

  36. de Oliveira MG, de Medeiros ML, Tavares EBG, Mónica FZ, Antunes E. Methylglyoxal, a reactive glucose metabolite, induces bladder overactivity in addition to inflammation in mice. Front Physiol. 2020;11:290.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Klee NS, McCarthy CG, Lewis S, McKenzie JL, Vincent JE, Webb RC. Urothelial senescence in the pathophysiology of diabetic bladder dysfunction-a novel hypothesis. Front Surg. 2018;5:72.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Geerlings SE, Meiland R, van Lith EC, Brouwer EC, Gaastra W, Hoepelman AI. Adherence of type 1-fimbriated Escherichia coli to uroepithelial cells: more in diabetic women than in control subjects. Diabetes Care. 2002;25(8):1405–9.

    Article  PubMed  Google Scholar 

  39. Yang Z, Dolber PC, Fraser MO. Diabetic urethropathy compounds the effects of diabetic cystopathy. J Urol. 2007;178(5):2213–9.

    Article  CAS  PubMed  Google Scholar 

  40. Cao N, Gu B, Gotoh D, Yoshimura N. Time-dependent changes of urethral function in diabetes mellitus: a review. Int Neurourol J. 2019;23(2):91–9.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Beshay E, Carrier S. Oxidative stress plays a role in diabetes-induced bladder dysfunction in a rat model. Urology. 2004;64(5):1062–7.

    Article  PubMed  Google Scholar 

  42. Yuan Z, Tang Z, He C, Tang W. Diabetic cystopathy: a review. J Diabetes. 2015;7(4):442–7.

    Article  PubMed  Google Scholar 

  43. Harding GK, Zhanel GG, Nicolle LE, Cheang M. Manitoba Diabetes Urinary Tract Infection Study Group. Antimicrobial treatment in diabetic women with asymptomatic bacteriuria. N Engl J Med. 2002;347(20):1576–83.

    Article  PubMed  Google Scholar 

  44. Nicolle LE, Gupta K, Bradley SF, Colgan R, DeMuri GP, Drekonja D, Eckert LO, Geerlings SE, Köves B, Hooton TM, Juthani-Mehta M, Knight SL, Saint S, Schaeffer AJ, Trautner B, Wullt B, Siemieniuk R. Clinical practice guideline for the management of asymptomatic bacteriuria: 2019 update by the Infectious Diseases Society of America. Clin Infect Dis. 2019;68(10):1611–5.

    Article  PubMed  Google Scholar 

  45. Tang H, Cui W, Li D, Wang T, Zhang J, Zhai S, Song Y. Sodium-glucose co-transporter 2 inhibitors in addition to insulin therapy for management of type 2 diabetes mellitus: a meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2017;19(1):142–7.

    Article  CAS  PubMed  Google Scholar 

  46. Donnan JR, Grandy CA, Chibrikov E, Pharm DCM, Aubrey-Bassler K, Johnston K, Swab M, Hache J, Curnew D, Nguyen H, Gamble JM. Dose response of sodium glucose cotransporter-2 inhibitors in relation to urinary tract infections: a systematic review and network meta-analysis of randomized controlled trials. CMAJ Open. 2018;6(4):E594–602.

    Article  PubMed  PubMed Central  Google Scholar 

  47. U.S. Food and Drug Administration. Drug safety communication: FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections. https://www.fda.gov/drugs/drug-safety-and-availability/fda-revises-labels-sglt2-inhibitors-diabetes-include-warnings-about-too-much-acid-blood-and-serious. Accessed 23 Feb 2021.

  48. Yap TL, Cromwell DC, Emberton M. A systematic review of the reliability of frequency-volume charts in urological research and its implications for the optimum chart duration. BJU Int. 2007;99(1):9–16.

    Article  PubMed  Google Scholar 

  49. van Haarst EP, Bosch JL. The optimal duration of frequency-volume charts related to compliance and reliability. Neurourol Urodyn. 2014;33(3):296–301.

    Article  PubMed  Google Scholar 

  50. Panicker JN, Fowler CJ, Kessler TM. Lower urinary tract dysfunction in the neurological patient: clinical assessment and management. Lancet Neurol. 2015;14(7):720–32.

    Article  PubMed  Google Scholar 

  51. Rosier PFWM, Schaefer W, Lose G, Goldman HB, Guralnick M, Eustice S, Dickinson T, Hashim H. International Continence Society Good Urodynamic Practices and Terms 2016: urodynamics, uroflowmetry, cystometry, and pressure-flow study. Neurourol Urodyn. 2017;36(5):1243–60.

    Article  PubMed  Google Scholar 

  52. Groen J, Pannek J, Castro Diaz D, Del Popolo G, Gross T, Hamid R, Karsenty G, Kessler TM, Schneider M, ‘t Hoen L, Blok B. Summary of European Association of Urology (EAU) guidelines on neuro-urology. Eur Urol. 2016;69(2):324–33.

    Article  PubMed  Google Scholar 

  53. Stöhrer M, Blok B, Castro-Diaz D, Chartier-Kastler E, Del Popolo G, Kramer G, Pannek J, Radziszewski P, Wyndaele JJ. EAU guidelines on neurogenic lower urinary tract dysfunction. Eur Urol. 2009;56(1):81–8.

    Article  PubMed  Google Scholar 

  54. Dumoulin C, Adewuyi T, Booth J, Bradley C, Burgio K, Hagen S, Hunter K, Imamura M, Morin M, Morkved S, Thakar R, Wallace S, Williams K. Adult conservative management. In: Abrams P, Cardozo L, Wagg A, Wein A, editors. Incontinence: 6th International consultation on incontinence, Tokyo, September 2016. Bristol: International Continence Society (ICS) and International Consultation on Urological Diseases (ICUD); 2017. p. 1443–628.

    Google Scholar 

  55. Coolen RL, Groen J, Scheepe JR, Blok BFM. Transcutaneous electrical nerve stimulation and percutaneous tibial nerve stimulation to treat idiopathic nonobstructive urinary retention: a systematic review. Eur Urol Focus. 2020;7(5):1184–94.

    Article  PubMed  Google Scholar 

  56. Wittig L, Carlson KV, Andrews JM, Crump RT, Baverstock RJ. Diabetic bladder dysfunction: a review. Urology. 2019;123:1–6.

    Article  PubMed  Google Scholar 

  57. Coyne KS, Thompson CL, Lai JS, Sexton CC. An overactive bladder symptom and health-related quality of life short-form: validation of the OAB-q SF. Neurourol Urodyn. 2015;34(3):255–63.

    Article  PubMed  Google Scholar 

  58. Abrams P, Avery K, Gardener N, Donovan J. ICIQ Advisory Board. The international consultation on incontinence modular questionnaire. J Urol. 2006;175(3 Pt 1):1063–6; www.iciq.net.

    Article  PubMed  Google Scholar 

  59. Greco C, Di Gennaro F, D’Amato C, Morganti R, Corradini D, Sun A, Longo S, Lauro D, Pierangeli G, Cortelli P, Spallone V. Validation of the Composite Autonomic Symptom Score 31 (COMPASS 31) for the assessment of symptoms of autonomic neuropathy in people with diabetes. Diabet Med. 2017;34(6):834–8.

    Article  CAS  PubMed  Google Scholar 

  60. Pop-Busui R, Boulton AJ, Feldman EL, Bril V, Freeman R, Malik RA, Sosenko JM, Ziegler D. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care. 2017;40(1):136–54.

    Article  CAS  PubMed  Google Scholar 

  61. Phelan S, Kanaya AM, Ma Y, Vittinghoff E, Barrett-Connor E, Wing R, Kusek JW, Orchard TJ, Crandall JP, Montez MG, Brown JS. Diabetes Prevention Program Research Group. Long-term prevalence and predictors of urinary incontinence among women in the Diabetes Prevention Program Outcomes Study. Int J Urol. 2015;22(2):206–12.

    Article  PubMed  Google Scholar 

  62. Breyer BN, Phelan S, Hogan PE, Rosen RC, Kitabchi AE, Wing RR, Brown JS. Look AHEAD Research Group. Intensive lifestyle intervention reduces urinary incontinence in overweight/obese men with type 2 diabetes: results from the Look AHEAD trial. J Urol. 2014;192(1):144–9.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Corona G, Tirabassi G, Santi D, Maseroli E, Gacci M, Dicuio M, Sforza A, Mannucci E, Maggi M. Sexual dysfunction in subjects treated with inhibitors of 5α-reductase for benign prostatic hyperplasia: a comprehensive review and meta-analysis. Andrology. 2017;5(4):671–8.

    Article  CAS  PubMed  Google Scholar 

  64. Han HH, Ko WJ, Yoo TK, Oh TH, Kim DY, Kwon DD, Byun SS, Kim SI, Jung TY. Factors associated with continuing medical therapy after transurethral resection of prostate. Urology. 2014;84(3):675–80.

    Article  PubMed  Google Scholar 

  65. Schneider T, Marschall-Kehrel D, Hanisch JU, Michel MC. Does concomitant diabetes affect treatment responses in overactive bladder patients? Int J Clin Pract. 2013;67(11):1138–43.

    Article  CAS  PubMed  Google Scholar 

  66. Wagg A, Nitti VW, Kelleher C, Castro-Diaz D, Siddiqui E, Berner T. Oral pharmacotherapy for overactive bladder in older patients: mirabegron as a potential alternative to antimuscarinics. Curr Med Res Opin. 2016;32(4):621–38.

    Article  CAS  PubMed  Google Scholar 

  67. Finazzi-Agrò E, Petta F, Sciobica F, Pasqualetti P, Musco S, Bove P. Percutaneous tibial nerve stimulation effects on detrusor overactivity incontinence are not due to a placebo effect: a randomized, double-blind, placebo controlled trial. J Urol. 2010;184(5):2001–6.

    Article  PubMed  Google Scholar 

  68. Peters KM, Macdiarmid SA, Wooldridge LS, Leong FC, Shobeiri SA, Rovner ES, Siegel SW, Tate SB, Jarnagin BK, Rosenblatt PL, Feagins BA. Randomized trial of percutaneous tibial nerve stimulation versus extended-release tolterodine: results from the overactive bladder innovative therapy trial. J Urol. 2009;182(3):1055–61.

    Article  CAS  PubMed  Google Scholar 

  69. Gaziev G, Topazio L, Iacovelli V, Asimakopoulos A, Di Santo A, De Nunzio C, Finazzi-Agrò E. Percutaneous Tibial Nerve Stimulation (PTNS) efficacy in the treatment of lower urinary tract dysfunctions: a systematic review. BMC Urol. 2013;13:61.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Daniels DH, Powell CR, Braasch MR, Kreder KJ. Sacral neuromodulation in diabetic patients: success and complications in the treatment of voiding dysfunction. Neurourol Urodyn. 2010;29(4):578–81.

    Article  PubMed  Google Scholar 

  71. Haraway AM, Clemens JQ, He C, Stroup C, Atiemo HO, Cameron AP. Differences in sacral neuromodulation device infection rates based on preoperative antibiotic selection. Int Urogynecol J. 2013;24(12):2081–5.

    Article  PubMed  Google Scholar 

  72. Wang CC, Liao CH, Kuo HC. Diabetes mellitus does not affect the efficacy and safety of intravesical onabotulinumtoxinA injection in patients with refractory detrusor overactivity. Neurourol Urodyn. 2014;33(8):1235–9.

    Article  CAS  PubMed  Google Scholar 

  73. Lamin E, Newman DK. Clean intermittent catheterization revisited. Int Urol Nephrol. 2016;48(6):931–9.

    Article  PubMed  Google Scholar 

  74. Pistolesi D, Barsotti M, Giannarini G, Mantovani M, Boggi U, Kessler TM, Selli C. Sacral neuromodulation enabling simultaneous pancreas and kidney transplantation: a first case. BMJ Case Rep. 2009;2009:bcr08.2008.0823.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Bump RC, Voss S, Beardsworth A, Manning M, Zhao YD, Chen W. Long-term efficacy of duloxetine in women with stress urinary incontinence. BJU Int. 2008;102(2):214–8.

    Article  CAS  PubMed  Google Scholar 

  76. Kokanali MK, Doğanay M, Aksakal O, Cavkaytar S, Topçu HO, Özer İ. Risk factors for mesh erosion after vaginal sling procedures for urinary incontinence. Eur J Obstet Gynecol Reprod Biol. 2014;177:146–50.

    Article  CAS  PubMed  Google Scholar 

  77. Corona G, Isidori AM, Aversa A, Bonomi M, Ferlin A, Foresta C, La Vignera S, Maggi M, Pivonello R, Vignozzi L, Lombardo F. Male and female sexual dysfunction in diabetic subjects: focus on new antihyperglycemic drugs. Rev Endocr Metab Disord. 2020;21(1):57–65.

    Article  PubMed  Google Scholar 

  78. McCabe MP, Sharlip ID, Atalla E, Balon R, Fisher AD, Laumann E, Lee SW, Lewis R, Segraves RT. Definitions of sexual dysfunctions in women and men: a consensus statement from the Fourth International Consultation on Sexual Medicine 2015. J Sex Med. 2016;13(2):135–43.

    Article  PubMed  Google Scholar 

  79. 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;151:54–61.

    Article  CAS  PubMed  Google Scholar 

  80. Kouidrat Y, Pizzol D, Cosco T, Thompson T, Carnaghi M, Bertoldo A, Solmi M, Stubbs B, Veronese N. High prevalence of erectile dysfunction in diabetes: a systematic review and meta-analysis of 145 studies. Diabet Med. 2017;34(9):1185–92.

    Article  CAS  PubMed  Google Scholar 

  81. Fedele D, Coscelli C, Santeusanio F, Bortolotti A, Chatenoud L, Colli E, Landoni M, Parazzini F. Erectile dysfunction in diabetic subjects in Italy. Gruppo Italiano Studio Deficit Erettile nei Diabetici. Diabetes Care. 1998;21(11):1973–7.

    Article  CAS  PubMed  Google Scholar 

  82. Parazzini F, Menchini Fabris F, Bortolotti A, Calabrò A, Chatenoud L, Colli E, Landoni M, Lavezzari M, Turchi P, Sessa A, Mirone V. Frequency and determinants of erectile dysfunction in Italy. Eur Urol. 2000;37(1):43–9.

    Article  CAS  PubMed  Google Scholar 

  83. Corona G, Giorda CB, Cucinotta D, Guida P, Nada E. Gruppo di studio SUBITO-DE. Sexual dysfunction at the onset of type 2 diabetes: the interplay of depression, hormonal and cardiovascular factors. J Sex Med. 2014;11(8):2065–73.

    Article  PubMed  Google Scholar 

  84. Skeldon SC, Detsky AS, Goldenberg SL, Law MR. Erectile dysfunction and undiagnosed diabetes, hypertension, and hypercholesterolemia. Ann Fam Med. 2015;13(4):331–5.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Johannes CB, Araujo AB, Feldman HA, Derby CA, Kleinman KP, McKinlay JB. Incidence of erectile dysfunction in men 40 to 69 years old: longitudinal results from the Massachusetts male aging study. J Urol. 2000;163(2):460–3.

    Article  CAS  PubMed  Google Scholar 

  86. Fedele D, Coscelli C, Cucinotta D, Forti G, Santeusanio F, Viaggi S, Fiori G, Velonà T, Lavezzari M. Diade Study Group. Incidence of erectile dysfunction in Italian men with diabetes. J Urol. 2001;166(4):1368–71.

    Article  CAS  PubMed  Google Scholar 

  87. Braun M, Wassmer G, Klotz T, Reifenrath B, Mathers M, Engelmann U. Epidemiology of erectile dysfunction: results of the ‘Cologne Male Survey’. Int J Impot Res. 2000;12(6):305–11.

    Article  CAS  PubMed  Google Scholar 

  88. Nicolosi A, Moreira ED Jr, Shirai M, Bin Mohd Tambi MI, Glasser DB. Epidemiology of erectile dysfunction in four countries: cross-national study of the prevalence and correlates of erectile dysfunction. Urology. 2003;61(1):201–6.

    Article  PubMed  Google Scholar 

  89. Malavige LS, Levy JC. Erectile dysfunction in diabetes mellitus. J Sex Med. 2009;6(5):1232–47.

    Article  PubMed  Google Scholar 

  90. Sarma AV, Hotaling JM, de Boer IH, Dunn RL, Oerline MK, Singh K, Goldberg J, Jacobson A, Braffett B, Herman WH, Pop-Busui R, Wessells H. DCCT/EDIC Research Group. Blood pressure, antihypertensive medication use, and risk of erectile dysfunction in men with type I diabetes. J Hypertens. 2019;37(5):1070–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Rosen RC, Wing RR, Schneider S, Wadden TA, Foster GD, West DS, Kitabchi AE, Brancati FL, Maschak-Carey BJ, Bahnson JL, Lewis CE, Gendrano Iii IN. Erectile dysfunction in type 2 diabetic men: relationship to exercise fitness and cardiovascular risk factors in the Look AHEAD trial. J Sex Med. 2009;6(5):1414–22.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Liu Q, Zhang Y, Wang J, Li S, Cheng Y, Guo J, Tang Y, Zeng H, Zhu Z. Erectile dysfunction and depression: a systematic review and meta-analysis. J Sex Med. 2018;15(8):1073–82.

    Article  PubMed  Google Scholar 

  93. Pouwer F. Depression: a common and burdensome complication of diabetes that warrants the continued attention of clinicians, researchers and healthcare policy makers. Diabetologia. 2017;60(1):30–4.

    Article  PubMed  Google Scholar 

  94. De Berardis G, Franciosi M, Belfiglio M, Di Nardo B, Greenfield S, Kaplan SH, Pellegrini F, Sacco M, Tognoni G, Valentini M, Nicolucci A. Quality of Care and Outcomes in Type 2 Diabetes (QuED) Study Group. Erectile dysfunction and quality of life in type 2 diabetic patients: a serious problem too often overlooked. Diabetes Care. 2002;25(2):284–91.

    PubMed  Google Scholar 

  95. De Berardis G, Pellegrini F, Franciosi M, Belfiglio M, Di Nardo B, Greenfield S, Kaplan SH, Rossi MC, Sacco M, Tognoni G, Valentini M, Nicolucci A. QuED (Quality of Care and Outcomes in Type 2 Diabetes) Study Group. Longitudinal assessment of quality of life in patients with type 2 diabetes and self-reported erectile dysfunction. Diabetes Care. 2005;28(11):2637–43.

    Article  PubMed  Google Scholar 

  96. Jacobson AM, Braffett BH, Cleary PA, Dunn RL, Larkin ME, Wessells H, Sarma AV. DCCT/EDIC Research Group. Relationship of urologic complications with health-related quality of life and perceived value of health in men and women with type 1 diabetes: the Diabetes Control and Complications Trial/Epidemiology of Interventions and Complications (DCCT/EDIC) cohort. Diabetes Care. 2015;38(10):1904–12.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Corona G, Rastrelli G, Isidori AM, Pivonello R, Bettocchi C, Reisman Y, Sforza A, Maggi M. Erectile dysfunction and cardiovascular risk: a review of current findings. Expert Rev Cardiovasc Ther. 2020;18(3):155–64.

    Article  CAS  PubMed  Google Scholar 

  98. Besiroglu H, Otunctemur A, Ozbek E. The relationship between metabolic syndrome, its components, and erectile dysfunction: a systematic review and a meta-analysis of observational studies. J Sex Med. 2015;12(6):1309–18.

    Article  CAS  PubMed  Google Scholar 

  99. Ning L, Yang L. Hypertension might be a risk factor for erectile dysfunction: a meta-analysis. Andrologia. 2017;49(4)

    Google Scholar 

  100. Wang XM, Bai YJ, Yang YB, Li JH, Tang Y, Han P. Alcohol intake and risk of erectile dysfunction: a dose-response meta-analysis of observational studies. Int J Impot Res. 2018;30(6):342–51.

    Article  PubMed  Google Scholar 

  101. Allen MS, Walter EE. Erectile dysfunction: an umbrella review of meta-analyses of risk-factors, treatment, and prevalence outcomes. J Sex Med. 2019;16(4):531–41.

    Article  PubMed  Google Scholar 

  102. Zhao B, Hong Z, Wei Y, Yu D, Xu J, Zhang W. Erectile dysfunction predicts cardiovascular events as an independent risk factor: a systematic review and meta-analysis. J Sex Med. 2019;16(7):1005–17.

    Article  PubMed  Google Scholar 

  103. Vlachopoulos CV, Terentes-Printzios DG, Ioakeimidis NK, Aznaouridis KA, Stefanadis CI. Prediction of cardiovascular events and all-cause mortality with erectile dysfunction: a systematic review and meta-analysis of cohort studies. Circ Cardiovasc Qual Outc. 2013;6(1):99–109.

    Article  Google Scholar 

  104. Montorsi P, Ravagnani PM, Galli S, Rotatori F, Briganti A, Salonia A, Rigatti P, Montorsi F. The artery size hypothesis: a macrovascular link between erectile dysfunction and coronary artery disease. Am J Cardiol. 2005;96(12B):19M–23M.

    Article  PubMed  Google Scholar 

  105. Frantzen J, Speel TG, Kiemeney LA, Meuleman EJ. Cardiovascular risk among men seeking help for erectile dysfunction. Ann Epidemiol. 2006;16(2):85–90.

    Article  CAS  PubMed  Google Scholar 

  106. Gazzaruso C, Solerte SB, Pujia A, Coppola A, Vezzoli M, Salvucci F, Valenti C, Giustina A, Garzaniti A. Erectile dysfunction as a predictor of cardiovascular events and death in diabetic patients with angiographically proven asymptomatic coronary artery disease: a potential protective role for statins and 5-phosphodiesterase inhibitors. J Am Coll Cardiol. 2008;51(21):2040–4.

    Article  PubMed  Google Scholar 

  107. Santi D, Granata AR, Guidi A, Pignatti E, Trenti T, Roli L, Bozic R, Zaza S, Pacchioni C, Romano S, Nofer JR, Rochira V, Carani C, Simoni M. Six months of daily treatment with vardenafil improves parameters of endothelial inflammation and of hypogonadism in male patients with type 2 diabetes and erectile dysfunction: a randomized, double-blind, prospective trial. Eur J Endocrinol. 2016;174(4):513–22.

    Article  CAS  PubMed  Google Scholar 

  108. Tzoumas N, Farrah TE, Dhaun N, Webb DJ. Established and emerging therapeutic uses of PDE type 5 inhibitors in cardiovascular disease. Br J Pharmacol. 2020;177(24):5467–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Pavy-Le Traon A, Fontaine S, Tap G, Guidolin B, Senard JM, Hanaire H. Cardiovascular autonomic neuropathy and other complications in type 1 diabetes. Clin Auton Res. 2010;20(3):153–60.

    Article  PubMed  Google Scholar 

  110. Wessells H, Penson DF, Cleary P, Rutledge BN, Lachin JM, McVary KT, Schade DS, Sarma AV. Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Effect of intensive glycemic therapy on erectile function in men with type 1 diabetes. J Urol. 2011;185(5):1828–34.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Azmi S, Ferdousi M, Alam U, Petropoulos IN, Ponirakis G, Marshall A, Asghar O, Fadavi H, Jones W, Tavakoli M, Boulton AJM, Jeziorska M, Soran H, Efron N, Malik RA. Small-fibre neuropathy in men with type 1 diabetes and erectile dysfunction: a cross-sectional study. Diabetologia. 2017;60(6):1094–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Dhage S, Ho JH, Ferdousi M, Kalteniece A, Azmi S, Adam S, Marshall A, Jeziorska M, Donn R, Soran H, Malik RA. Small fibre pathology is associated with erectile dysfunction in men with type 2 diabetes. Diabetes Metab Res Rev. 2020;36(3):e3263.

    Article  CAS  PubMed  Google Scholar 

  113. Wellmer A, Sharief MK, Knowles CH, Misra VP, Kopelman P, Ralph D, Anand P. Quantitative sensory and autonomic testing in male diabetic patients with erectile dysfunction. BJU Int. 1999;83(1):66–70.

    Article  CAS  PubMed  Google Scholar 

  114. Sáenz de Tejada I, Angulo J, Cellek S, González-Cadavid N, Heaton J, Pickard R, Simonsen U. Pathophysiology of erectile dysfunction. J Sex Med. 2005;2(1):26–39.

    Article  PubMed  Google Scholar 

  115. Saenz de Tejada I, Goldstein I, Azadzoi K, Krane RJ, Cohen RA. Impaired neurogenic and endothelium-mediated relaxation of penile smooth muscle from diabetic men with impotence. N Engl J Med. 1989;320(16):1025–30.

    Article  CAS  PubMed  Google Scholar 

  116. Ganz P. Erectile dysfunction: pathophysiologic mechanisms pointing to underlying cardiovascular disease. Am J Cardiol. 2005;96(12B):8M–12M.

    Article  CAS  PubMed  Google Scholar 

  117. Andersson KE, Wagner G. Physiology of penile erection. Physiol Rev. 1995;75(1):191–236.

    Article  CAS  PubMed  Google Scholar 

  118. Dean RC, Lue TF. Physiology of penile erection and pathophysiology of erectile dysfunction. Urol Clin North Am. 2005;32(4):379–95.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Isidori AM, Buvat J, Corona G, Goldstein I, Jannini EA, Lenzi A, Porst H, Salonia A, Traish AM, Maggi M. A critical analysis of the role of testosterone in erectile function: from pathophysiology to treatment-a systematic review. Eur Urol. 2014;65(1):99–112.

    Article  CAS  PubMed  Google Scholar 

  120. Sopko NA, Hannan JL, Bivalacqua TJ. Understanding and targeting the Rho kinase pathway in erectile dysfunction. Nat Rev Urol. 2014;11(11):622–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Ludwig W, Phillips M. Organic causes of erectile dysfunction in men under 40. Urol Int. 2014;92(1):1–6.

    Article  PubMed  Google Scholar 

  122. Jannini EA, McCabe MP, Salonia A, Montorsi F, Sachs BD. Organic vs. psychogenic? The Manichean diagnosis in sexual medicine. J Sex Med. 2010;7(5):1726–33.

    Article  PubMed  Google Scholar 

  123. Gupta BP, Murad MH, Clifton MM, Prokop L, Nehra A, Kopecky SL. The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction: a systematic review and meta-analysis. Arch Intern Med. 2011;171(20):1797–803.

    Article  PubMed  Google Scholar 

  124. Maiorino MI, Bellastella G, Giugliano D, Esposito K. From inflammation to sexual dysfunctions: a journey through diabetes, obesity, and metabolic syndrome. J Endocrinol Investig. 2018;41(11):1249–58.

    Article  CAS  Google Scholar 

  125. Dhindsa S, Ghanim H, Batra M, Dandona P. Hypogonadotropic hypogonadism in men with diabesity. Diabetes Care. 2018;41(7):1516–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Brüning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, Klein R, Krone W, Müller-Wieland D, Kahn CR. Role of brain insulin receptor in control of body weight and reproduction. Science. 2000;289(5487):2122–5.

    Article  PubMed  Google Scholar 

  127. Isidori AM, Caprio M, Strollo F, Moretti C, Frajese G, Isidori A, Fabbri A. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab. 1999;84(10):3673–80.

    CAS  PubMed  Google Scholar 

  128. Zhai L, Zhao J, Zhu Y, Liu Q, Niu W, Liu C, Wang Y. Downregulation of leptin receptor and kisspeptin/GPR54 in the murine hypothalamus contributes to male hypogonadism caused by high-fat diet-induced obesity. Endocrine. 2018;62(1):195–206.

    Article  CAS  PubMed  Google Scholar 

  129. Simó R, Sáez-López C, Barbosa-Desongles A, Hernández C, Selva DM. Novel insights in SHBG regulation and clinical implications. Trends Endocrinol Metab. 2015;26(7):376–83.

    Article  PubMed  Google Scholar 

  130. Burnett AL, Nehra A, Breau RH, Culkin DJ, Faraday MM, Hakim LS, Heidelbaugh J, Khera M, McVary KT, Miner MM, Nelson CJ, Sadeghi-Nejad H, Seftel AD, Shindel AW. Erectile dysfunction: AUA guideline. J Urol. 2018;200(3):633–41.

    Article  PubMed  Google Scholar 

  131. Nehra A, Jackson G, Miner M, Billups KL, Burnett AL, Buvat J, Carson CC, Cunningham GR, Ganz P, Goldstein I, Guay AT, Hackett G, Kloner RA, Kostis J, Montorsi P, Ramsey M, Rosen R, Sadovsky R, Seftel AD, Shabsigh R, Vlachopoulos C, Wu FC. The Princeton III Consensus recommendations for the management of erectile dysfunction and cardiovascular disease. Mayo Clin Proc. 2012;87(8):766–78.

    Article  PubMed  PubMed Central  Google Scholar 

  132. Althof SE, Rosen RC, Perelman MA, Rubio-Aurioles E. Standard operating procedures for taking a sexual history. J Sex Med. 2013;10(1):26–35.

    Article  PubMed  Google Scholar 

  133. Cappelleri JC, Rosen RC. The Sexual Health Inventory for Men (SHIM): a 5-year review of research and clinical experience. Int J Impot Res. 2005;17(4):307–19.

    Article  CAS  PubMed  Google Scholar 

  134. Petrone L, Mannucci E, Corona G, Bartolini M, Forti G, Giommi R, Maggi M. Structured interview on erectile dysfunction (SIEDY): a new, multidimensional instrument for quantification of pathogenetic issues on erectile dysfunction. Int J Impot Res. 2003;15(3):210–20.

    Article  CAS  PubMed  Google Scholar 

  135. Ghanem HM, Salonia A, Martin-Morales A. SOP: physical examination and laboratory testing for men with erectile dysfunction. J Sex Med. 2013;10(1):108–10.

    Article  PubMed  Google Scholar 

  136. Gratzke C, Bachmann A, Descazeaud A, Drake MJ, Madersbacher S, Mamoulakis C, Oelke M, Tikkinen KAO, Gravas S. EAU guidelines on the assessment of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction. Eur Urol. 2015;67(6):1099–109.

    Article  PubMed  Google Scholar 

  137. Spallone V, Ziegler D, Freeman R, Bernardi L, Frontoni S, Pop-Busui R, Stevens M, Kempler P, Hilsted J, Tesfaye S, Low P, Valensi P. Toronto Consensus Panel on Diabetic Neuropathy. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev. 2011;27(7):639–53.

    Article  PubMed  Google Scholar 

  138. Kamenov ZA. A comprehensive review of erectile dysfunction in men with diabetes. Exp Clin Endocrinol Diabetes. 2015;123(3):141–58.

    CAS  PubMed  Google Scholar 

  139. Corona G, Goulis DG, Huhtaniemi I, Zitzmann M, Toppari J, Forti G, Vanderschueren D, Wu FC. European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males: endorsing organization: European Society of Endocrinology. Andrology. 2020;8(5):970–87.

    Article  PubMed  Google Scholar 

  140. Bella AJ, Lee JC, Carrier S, Bénard F, Brock GB. 2015 CUA Practice guidelines for erectile dysfunction. Can Urol Assoc J. 2015;9(1-2):23–9.

    Article  PubMed  PubMed Central  Google Scholar 

  141. Corona G, Fagioli G, Mannucci E, Romeo A, Rossi M, Lotti F, Sforza A, Morittu S, Chiarini V, Casella G, Di Pasquale G, Bandini E, Forti G, Maggi M. Penile Doppler ultrasound in patients with erectile dysfunction (ED): role of peak systolic velocity measured in the flaccid state in predicting arteriogenic ED and silent coronary artery disease. J Sex Med. 2008;5(11):2623–34.

    Article  PubMed  Google Scholar 

  142. Jung DC, Park SY, Lee JY. Penile Doppler ultrasonography revisited. Ultrasonography. 2018;37(1):16–24.

    Article  PubMed  Google Scholar 

  143. Hatzimouratidis K, Salonia A, Adaikan G, Buvat J, Carrier S, El-Meliegy A, McCullough A, Torres LO, Khera M. Pharmacotherapy for erectile dysfunction: recommendations from the Fourth International Consultation for Sexual Medicine (ICSM 2015). J Sex Med. 2016;13(4):465–88.

    Article  PubMed  Google Scholar 

  144. Algeffari M, Jayasena CN, MacKeith P, Thapar A, Dhillo WS, Oliver N. Testosterone therapy for sexual dysfunction in men with Type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabet Med. 2018;35(2):195–202.

    Article  CAS  PubMed  Google Scholar 

  145. Duncan C, Omran GJ, Teh J, Davis NF, Bolton DM, Lawrentschuk N. Erectile dysfunction: a global review of intracavernosal injectables. World J Urol. 2019;37(6):1007–14.

    Article  PubMed  Google Scholar 

  146. Levine LA, Becher EF, Bella AJ, Brant WO, Kohler TS, Martinez-Salamanca JI, Trost L, Morey AF. Penile prosthesis surgery: current recommendations from the international consultation on sexual medicine. J Sex Med. 2016;13(4):489–518.

    Article  PubMed  Google Scholar 

  147. Silva AB, Sousa N, Azevedo LF, Martins C. Physical activity and exercise for erectile dysfunction: systematic review and meta-analysis. Br J Sports Med. 2017;51(19):1419–24.

    Article  PubMed  Google Scholar 

  148. Maiorino MI, Bellastella G, Esposito K. Diabetes and sexual dysfunction: current perspectives. Diabetes Metab Syndr Obes. 2014;7:95–105.

    PubMed  PubMed Central  Google Scholar 

  149. Look AHEAD Research Group, Wing RR. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Arch Intern Med. 2010;170(17):1566–75.

    Google Scholar 

  150. Boddi V, Castellini G, Casale H, Rastrelli G, Boni L, Corona G, Maggi M. An integrated approach with vardenafil orodispersible tablet and cognitive behavioral sex therapy for treatment of erectile dysfunction: a randomized controlled pilot study. Andrology. 2015;3(5):909–18.

    Article  CAS  PubMed  Google Scholar 

  151. Chen L, Staubli SE, Schneider MP, Kessels AG, Ivic S, Bachmann LM, Kessler TM. Phosphodiesterase 5 inhibitors for the treatment of erectile dysfunction: a trade-off network meta-analysis. Eur Urol. 2015;68(4):674–80.

    Article  CAS  PubMed  Google Scholar 

  152. Zucchi A, Costantini E, Scroppo FI, Silvani M, Kopa Z, Illiano E, Petrillo MG, Cari L, Nocentini G. The first-generation phosphodiesterase 5 inhibitors and their pharmacokinetic issue. Andrology. 2019;7(6):804–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Hirano T, Mori Y. Anti-atherogenic and anti-inflammatory properties of glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, and dipeptidyl peptidase-4 inhibitors in experimental animals. J Diabetes Investig. 2016;7(Suppl 1):80–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Liao X, Qiu S, Bao Y, Wang W, Yang L, Wei Q. Comparative efficacy and safety of phosphodiesterase type 5 inhibitors for erectile dysfunction in diabetic men: a Bayesian network meta-analysis of randomized controlled trials. World J Urol. 2019;37(6):1061–74.

    Article  CAS  PubMed  Google Scholar 

  155. Giannetta E, Feola T, Gianfrilli D, Pofi R, Dall’Armi V, Badagliacca R, Barbagallo F, Lenzi A, Isidori AM. Is chronic inhibition of phosphodiesterase type 5 cardioprotective and safe? A meta-analysis of randomized controlled trials. BMC Med. 2014;12:185.

    Article  PubMed  PubMed Central  Google Scholar 

  156. Liu B, Zhu L, Zhong J, Zeng G, Deng T. The association between phosphodiesterase type 5 inhibitor use and risk of non-arteritic anterior ischemic optic neuropathy: a systematic review and meta-analysis. Sex Med. 2018;6(3):185–92.

    Article  PubMed  PubMed Central  Google Scholar 

  157. Manna S, Gray ML, Kaul VF, Wanna G. Phosphodiesterase-5 (PDE-5) Inhibitors and ototoxicity: a systematic review. Otol Neurotol. 2019;40(3):276–83.

    Article  PubMed  Google Scholar 

  158. Giuliano F, Jackson G, Montorsi F, Martin-Morales A, Raillard P. Safety of sildenafil citrate: review of 67 double-blind placebo-controlled trials and the postmarketing safety database. Int J Clin Pract. 2010;64(2):240–55.

    Article  CAS  PubMed  Google Scholar 

  159. Lee M, Sharifi R. Non-invasive management options for erectile dysfunction when a phosphodiesterase type 5 inhibitor fails. Drugs Aging. 2018;35(3):175–87.

    Article  CAS  PubMed  Google Scholar 

  160. Hackett G, Cole N, Saghir A, Jones P, Strange RC, Ramachandran S. Testosterone replacement therapy: improved sexual desire and erectile function in men with type 2 diabetes following a 30-week randomized placebo-controlled study. Andrology. 2017;5(5):905–13.

    Article  CAS  PubMed  Google Scholar 

  161. Spitzer M, Basaria S, Travison TG, Davda MN, Paley A, Cohen B, Mazer NA, Knapp PE, Hanka S, Lakshman KM, Ulloor J, Zhang A, Orwoll K, Eder R, Collins L, Mohammed N, Rosen RC, DeRogatis L, Bhasin S. Effect of testosterone replacement on response to sildenafil citrate in men with erectile dysfunction: a parallel, randomized trial. Ann Intern Med. 2012;157(10):681–91.

    Article  PubMed  Google Scholar 

  162. Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, Snyder PJ, Swerdloff RS, Wu FC, Yialamas MA. Testosterone therapy in men with hypogonadism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715–44.

    Article  PubMed  Google Scholar 

  163. Saad F, Yassin A, Almehmadi Y, Doros G, Gooren L. Effects of long-term testosterone replacement therapy, with a temporary intermission, on glycemic control of nine hypogonadal men with type 1 diabetes mellitus - a series of case reports. Aging Male. 2015;18(3):164–8.

    Article  CAS  PubMed  Google Scholar 

  164. Padma-Nathan H, Hellstrom WJ, Kaiser FE, Labasky RF, Lue TF, Nolten WE, Norwood PC, Peterson CA, Shabsigh R, Tam PY, Place VA, Gesundheit N. Treatment of men with erectile dysfunction with transurethral alprostadil. Medicated Urethral System for Erection (MUSE) Study Group. N Engl J Med. 1997;336(1):1–7.

    Article  CAS  PubMed  Google Scholar 

  165. Heaton JP, Lording D, Liu SN, Litonjua AD, Guangwei L, Kim SC, Kim JJ, Zhi-Zhou S, Israr D, Niazi D, Rajatanavin R, Suyono S, Benard F, Casey R, Brock G, Belanger A. Intracavernosal alprostadil is effective for the treatment of erectile dysfunction in diabetic men. Int J Impot Res. 2001;13(6):317–21.

    Article  CAS  PubMed  Google Scholar 

  166. Moncada I, Martinez-Salamanca J, Ruiz-Castañe E, Romero J. Combination therapy for erectile dysfunction involving a PDE5 inhibitor and alprostadil. Int J Impot Res. 2018;30(5):203–8.

    Article  CAS  PubMed  Google Scholar 

  167. 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.

    Article  PubMed  Google Scholar 

  168. Scherzer ND, Dick B, Gabrielson AT, Alzweri LM, Hellstrom WJG. Penile prosthesis complications: planning, prevention, and decision making. Sex Med Rev. 2019;7(2):349–59.

    Article  PubMed  Google Scholar 

  169. Dicks B, Bastuba M, Goldstein I. Penile revascularization--contemporary update. Asian J Androl. 2013;15(1):5–9.

    Article  PubMed  Google Scholar 

  170. Hsieh CH, Hsu GL, Chang SJ, Yang SS, Liu SP, Hsieh JT. Surgical niche for the treatment of erectile dysfunction. Int J Urol. 2020;27(2):117–33.

    Article  PubMed  Google Scholar 

  171. Dong L, Chang D, Zhang X, Li J, Yang F, Tan K, Yang Y, Yong S, Yu X. Effect of low-intensity extracorporeal shock wave on the treatment of erectile dysfunction: a systematic review and meta-analysis. Am J Mens Health. 2019;13(2):1557988319846749.

    Article  PubMed  PubMed Central  Google Scholar 

  172. Bahk JY, Jung JH, Han H, Min SK, Lee YS. Treatment of diabetic impotence with umbilical cord blood stem cell intracavernosal transplant: preliminary report of 7 cases. Exp Clin Transplant. 2010;8(2):150–60.

    PubMed  Google Scholar 

  173. Huang CY, Shih CM, Tsao NW, Lin YW, Huang PH, Wu SC, Lee AW, Kao YT, Chang NC, Nakagami H, Morishita R, Ou KL, Hou WC, Lin CY, Shyu KG, Lin FY. Dipeptidyl peptidase-4 inhibitor improves neovascularization by increasing circulating endothelial progenitor cells. Br J Pharmacol. 2012;167(7):1506–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Assaly R, Gorny D, Compagnie S, Mayoux E, Bernabe J, Alexandre L, Giuliano F, Behr-Roussel D. The favorable effect of empagliflozin on erectile function in an experimental model of type 2 diabetes. J Sex Med. 2018;15(9):1224–34.

    Article  PubMed  Google Scholar 

  175. Shao N, Yu XY, Yu YM, Li BW, Pan J, Wu WH, Zhang HJ, Ma XF, Hao M, Kuang HY. Short-term combined treatment with exenatide and metformin is superior to glimepiride combined metformin in improvement of serum testosterone levels in type 2 diabetic patients with obesity. Andrologia. 2018;50(7):e13039.

    Article  CAS  PubMed  Google Scholar 

  176. Caparrotta TM, Greenhalgh AM, Osinski K, Gifford RM, Moser S, Wild SH, Reynolds RM, Webb DJ, Colhoun HM. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) exposure and outcomes in type 2 diabetes: a systematic review of population-based observational studies. Diabetes Ther. 2021;12:991.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Althof SE, McMahon CG, Waldinger MD, Serefoglu EC, Shindel AW, Adaikan PG, Becher E, Dean J, Giuliano F, Hellstrom WJ, Giraldi A, Glina S, Incrocci L, Jannini E, McCabe M, Parish S, Rowland D, Segraves RT, Sharlip I, Torres LO. An update of the International Society of Sexual Medicine’s guidelines for the diagnosis and treatment of premature ejaculation (PE). J Sex Med. 2014;11(6):1392–422.

    Article  PubMed  Google Scholar 

  178. Sansone A, Aversa A, Corona G, Fisher AD, Isidori AM, La Vignera S, Limoncin E, Maggi M, Merico M, Jannini EA. Management of premature ejaculation: a clinical guideline from the Italian Society of Andrology and Sexual Medicine (SIAMS). J Endocrinol Investig. 2020;44:1103.

    Article  Google Scholar 

  179. McCabe MP, Sharlip ID, Lewis R, Atalla E, Balon R, Fisher AD, Laumann E, Lee SW, Segraves RT. Incidence and prevalence of sexual dysfunction in women and men: a consensus statement from the Fourth International Consultation on Sexual Medicine 2015. J Sex Med. 2016;13(2):144–52.

    Article  PubMed  Google Scholar 

  180. Malavige LS, Jayaratne SD, Kathriarachchi ST, Sivayogan S, Fernando DJ, Levy JC. Erectile dysfunction among men with diabetes is strongly associated with premature ejaculation and reduced libido. J Sex Med. 2008;5(9):2125–34.

    Article  PubMed  Google Scholar 

  181. Bellastella G, Maiorino MI, Olita L, Della Volpe E, Giugliano D, Esposito K. Premature ejaculation is associated with glycemic control in Type 1 diabetes. J Sex Med. 2015;12(1):93–9.

    Article  CAS  PubMed  Google Scholar 

  182. Di Sante S, Mollaioli D, Gravina GL, Ciocca G, Limoncin E, Carosa E, Lenzi A, Jannini EA. Epidemiology of delayed ejaculation. Transl Androl Urol. 2016;5(4):541–8.

    Article  PubMed  PubMed Central  Google Scholar 

  183. Sexton WJ, Jarow JP. Effect of diabetes mellitus upon male reproductive function. Urology. 1997;49(4):508–13.

    Article  CAS  PubMed  Google Scholar 

  184. Lindau ST, Tang H, Gomero A, Vable A, Huang ES, Drum ML, Qato DM, Chin MH. Sexuality among middle-aged and older adults with diagnosed and undiagnosed diabetes: a national, population-based study. Diabetes Care. 2010;33(10):2202–10.

    Article  PubMed  PubMed Central  Google Scholar 

  185. Agochukwu-Mmonu N, Malaeb BS, Hotaling JM, Braffett BH, Holt SK, Dunn RL, Palmer MR, Martin CL, Jacobson AM, Herman WH, Wessells H. Sarma AV; and the DCCT/EDIC Research Group. Risk factors for orgasmic and concomitant erectile dysfunction in men with type 1 diabetes: a cross-sectional study. Int J Impot Res. 2021;33(1):59–66.

    Article  PubMed  Google Scholar 

  186. Alwaal A, Breyer BN, Lue TF. Normal male sexual function: emphasis on orgasm and ejaculation. Fertil Steril. 2015;104(5):1051–60.

    Article  PubMed  PubMed Central  Google Scholar 

  187. Kempeneers P, Andrianne R, Cuddy M, Blairy S. Sexual cognitions, trait anxiety, sexual anxiety, and distress in men with different subtypes of premature ejaculation and in their partners. J Sex Marital Ther. 2018;44(4):319–32.

    Article  PubMed  Google Scholar 

  188. Hull EM, Lumley LA, Matuszewich L, Dominguez J, Moses J, Lorrain DS. The roles of nitric oxide in sexual function of male rats. Neuropharmacology. 1994;33(11):1499–504.

    Article  CAS  PubMed  Google Scholar 

  189. Gray M, Zillioux J, Khourdaji I, Smith RP. Contemporary management of ejaculatory dysfunction. Transl Androl Urol. 2018;7(4):686–702.

    Article  PubMed  PubMed Central  Google Scholar 

  190. Althof SE, McMahon CG. Contemporary management of disorders of male orgasm and ejaculation. Urology. 2016;93:9–21.

    Article  PubMed  Google Scholar 

  191. Arafa M, El Tabie O. Medical treatment of retrograde ejaculation in diabetic patients: a hope for spontaneous pregnancy. J Sex Med. 2008;5(1):194–8.

    Article  CAS  PubMed  Google Scholar 

  192. Kurbatov D, Russo GI, Galstyan GR, Rozhivanov R, Lepetukhin A, Dubsky S, Shwartz YG, Cimino S, Morgia G, Sansalone S. Correction of retrograde ejaculation in patients with diabetes mellitus using endourethral collagen injection: preliminary results. J Sex Med. 2015;12(11):2126–9.

    Article  CAS  PubMed  Google Scholar 

  193. Parish SJ, Hahn SR, Goldstein SW, Giraldi A, Kingsberg SA, Larkin L, Minkin MJ, Brown V, Christiansen K, Hartzell-Cushanick R, Kelly-Jones A, Rullo J, Sadovsky R, Faubion SS. The International Society for the Study of women’s sexual health process of care for the identification of sexual concerns and problems in women. Mayo Clin Proc. 2019;94(5):842–56.

    Article  PubMed  Google Scholar 

  194. Pontiroli AE, Cortelazzi D, Morabito A. Female sexual dysfunction and diabetes: a systematic review and meta-analysis. J Sex Med. 2013;10(4):1044–51.

    Article  PubMed  Google Scholar 

  195. Rahmanian E, Salari N, Mohammadi M, Jalali R. Evaluation of sexual dysfunction and female sexual dysfunction indicators in women with type 2 diabetes: a systematic review and meta-analysis. Diabetol Metab Syndr. 2019;11:73.

    Article  PubMed  PubMed Central  Google Scholar 

  196. Enzlin P, Rosen R, Wiegel M, Brown J, Wessells H, Gatcomb P, Rutledge B, Chan KL, Cleary PA. DCCT/EDIC Research Group. Sexual dysfunction in women with type 1 diabetes: long-term findings from the DCCT/EDIC study cohort. Diabetes Care. 2009;32(5):780–5.

    Article  PubMed  PubMed Central  Google Scholar 

  197. Maiorino MI, Bellastella G, Castaldo F, Petrizzo M, Giugliano D, Esposito K. Sexual function in young women with type 1 diabetes: the METRO study. J Endocrinol Investig. 2017;40(2):169–77.

    Article  CAS  Google Scholar 

  198. Bąk E, Marcisz C, Krzemińska S, Dobrzyn-Matusiak D, Foltyn A, Drosdzol-Cop A. Relationships of sexual dysfunction with depression and acceptance of illness in women and men with type 2 diabetes mellitus. Int J Environ Res Public Health. 2017;14(9):1073.

    Article  PubMed  PubMed Central  Google Scholar 

  199. Basson R. Clinical practice. Sexual desire and arousal disorders in women. N Engl J Med. 2006;354(14):1497–506.

    Article  CAS  PubMed  Google Scholar 

  200. Maseroli E, Scavello I, Vignozzi L. Cardiometabolic risk and female sexuality-Part II. Understanding (and overcoming) gender differences: the key role of an adequate methodological approach. Sex Med Rev. 2018;6(4):525–34.

    Article  PubMed  Google Scholar 

  201. Davis SR, Davison SL, Donath S, Bell RJ. Circulating androgen levels and self-reported sexual function in women. JAMA. 2005;294(1):91–6.

    Article  CAS  PubMed  Google Scholar 

  202. Barbagallo F, Mongioì LM, Cannarella R, La Vignera S, Condorelli RA, Calogero AE. Sexual dysfunction in diabetic women: an update on current knowledge. Diabetology. 2020;1(1):11–21.

    Article  Google Scholar 

  203. Maseroli E, Fanni E, Cipriani S, Scavello I, Pampaloni F, Battaglia C, Fambrini M, Mannucci E, Jannini EA, Maggi M, Vignozzi L. Cardiometabolic risk and female sexuality: focus on clitoral vascular resistance. J Sex Med. 2016;13(11):1651–61.

    Article  PubMed  Google Scholar 

  204. Isidori AM, Pozza C, Esposito K, Giugliano D, Morano S, Vignozzi L, Corona G, Lenzi A, Jannini EA. Development and validation of a 6-item version of the female sexual function index (FSFI) as a diagnostic tool for female sexual dysfunction. J Sex Med. 2010;7(3):1139–46.

    Article  PubMed  Google Scholar 

  205. Woodard TL, Diamond MP. Physiologic measures of sexual function in women: a review. Fertil Steril. 2009;92(1):19–34.

    Article  PubMed  Google Scholar 

  206. Caruso S, Rugolo S, Mirabella D, Intelisano G, Di Mari L, Cianci A. Changes in clitoral blood flow in premenopausal women affected by type 1 diabetes after single 100-mg administration of sildenafil. Urology. 2006;68(1):161–5.

    Article  PubMed  Google Scholar 

  207. Krakowsky Y, Grober ED. A practical guide to female sexual dysfunction: an evidence-based review for physicians in Canada. Can Urol Assoc J. 2018;12(6):211–6.

    Article  PubMed  PubMed Central  Google Scholar 

  208. Wing RR, Bond DS, Gendrano IN III, Wadden T, Bahnson J, Lewis CE, Brancati F, Schneider S, Kitabchi AE, Van Dorsten B, Rosen RC. Sexual Dysfunction Subgroup of the Look AHEAD Research Group. Effect of intensive lifestyle intervention on sexual dysfunction in women with type 2 diabetes: results from an ancillary Look AHEAD study. Diabetes Care. 2013;36(10):2937–44.

    Article  PubMed  PubMed Central  Google Scholar 

  209. Krysiak R, Drosdzol-Cop A, Skrzypulec-Plinta V, Okopień B. Sexual functioning and depressive symptoms in women with diabetes and prediabetes receiving metformin therapy: a pilot study. Exp Clin Endocrinol Diabetes. 2017;125(1):42–8.

    CAS  PubMed  Google Scholar 

  210. Islam RM, Bell RJ, Green S, Page MJ, Davis SR. Safety and efficacy of testosterone for women: a systematic review and meta-analysis of randomised controlled trial data. Lancet Diabetes Endocrinol. 2019;7(10):754–66.

    Article  CAS  PubMed  Google Scholar 

  211. Davis SR, Baber R, Panay N, Bitzer J, Cerdas Perez S, Islam RM, Kaunitz AM, Kingsberg SA, Lambrinoudaki I, Liu J, Parish SJ, Pinkerton J, Rymer J, Simon JA, Vignozzi L, Wierman ME. Global consensus position statement on the use of testosterone therapy for women. Climacteric. 2019;22(5):429–34.

    Article  PubMed  Google Scholar 

  212. Chivers ML, Rosen RC. Phosphodiesterase type 5 inhibitors and female sexual response: faulty protocols or paradigms? J Sex Med. 2010;7(2 Pt 2):858–72.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Endocrinology, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy

    Vincenza Spallone

  2. Urology, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy

    Enrico Finazzi Agrò & Luca Orecchia

  3. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

    Roberta Centello, Claudio Lecis & Andrea M. Isidori

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  1. Vincenza Spallone
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  2. Enrico Finazzi Agrò
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  3. Roberta Centello
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  4. Claudio Lecis
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  5. Luca Orecchia
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  6. Andrea M. Isidori
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Correspondence to Vincenza Spallone .

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Editors and Affiliations

  1. Royal Hallamshire Hospital, Sheffield Teaching Hospitals and the University of Sheffield Director of Diabetes Research, Sheffield, UK

    Solomon Tesfaye

  2. Beth Israel Deaconess Medical Center, Boston, MA, USA

    Christopher H. Gibbons

  3. Weill Cornell Medicine, Cornell University, Doha, Qatar

    Rayaz Ahmed Malik

  4. Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Aristidis Veves

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Spallone, V., Finazzi Agrò, E., Centello, R., Lecis, C., Orecchia, L., Isidori, A.M. (2023). Diabetic Neuropathy: Clinical Management—Genitourinary Dysfunction in Diabetes. In: Tesfaye, S., Gibbons, C.H., Malik, R.A., Veves, A. (eds) Diabetic Neuropathy. Contemporary Diabetes. Humana, Cham. https://doi.org/10.1007/978-3-031-15613-7_28

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