Erectile Dysfunction

Canadian Diabetes Association Clinical Practice Guidelines Expert Committee

Gerald Brock MD, FRCSC William Harper MD, FRCPC

  • Key Messages
  • Recommendations
  • Figures
  • Full Text
  • References

Key Messages

  • Erectile dysfunction (ED) affects approximately 34% to 45% of adult men with diabetes, has been demonstrated to negatively impact quality of life among those affected across all age strata and may be the earliest sign of cardiovascular disease.
  • All adult men with diabetes should be regularly screened for ED with a sexual function history. Those with ED should be investigated for hypogonadism.
  • The current mainstay of therapy is phosphodiesterase type 5 inhibitors. They have been shown to have major impacts on erectile function and quality of life, with a low reported side effect profile, and should be offered as first-line therapy to men with diabetes wishing treatment for ED.

Introduction

Erectile dysfunction (ED) affects approximately 34% to 45% of men with diabetes and has been demonstrated to negatively impact quality of life among those affected across all age strata, with a greater likelihood among men with diabetes that their ED is permanent (1). Recent reports describe up to one-third of newly diagnosed men with diabetes have ED at presentation (2), with upward of 50% of men having ED by year 6 after diagnosis (3). Furthermore, studies indicate that 40% of men with diabetes >60 years of age have complete ED (4–12). Recent studies have reported that alteration of the cyclic guanosine monophosphate (cGMP(/nitric acid (NO) pathway among men with diabetes with impaired vascular relaxation is related to endothelial dysfunction (13–15). Among the population with diabetes, risk factors include increasing age, duration of diabetes, poor glycemic control, cigarette smoking, hypertension, dyslipidemia, androgen deficiency states (16) and cardiovascular (CV) disease (8,10,17,18). ED as a marker of potential CV events has been reported by numerous investigators (19–26). In fact, ED has been shown to be significantly associated with all-cause mortality and CV events (27,28). Diabetic retinopathy has been shown to correlate with the presence of ED (8,10,29). Organic causes of ED include microvascular and macrovascular disease, and neuropathy. In addition, psychological or situational factors may cause or contribute to ED.

In spite of the overwhelming amount of data linking ED and diabetes, this remains a subject often neglected by clinicians treating the population with diabetes (30).

Compared with the general population, multiple studies have reported men with diabetes having higher rates of hypogonadism (16,31–34). Interestingly, a recent report describes a correlation between glycemic control and testosterone levels (35). Importantly, phosphodiesterase type 5 (PDE5) inhibitors appear to be less effective in hypogonadal states (32,34,36), where treatment of nonresponders to PDE5 inhibitors with testosterone replacement is successful in roughly 50% of individuals. In addition, ED is a side effect of many drugs commonly prescribed to men with diabetes, such as some antihypertensives and antidepressants.

Screening

All adult men with diabetes should be regularly screened for ED with a sexual function history. Screening for ED in men with type 2 diabetes should begin at diagnosis of diabetes. Validated questionnaires (e.g. International Index of Erectile Function (37,38) or Sexual Health Inventory for Men (39) ) have been shown to be both sensitive and specific in determining the presence of ED and providing a means of assessing response to therapy. Men with diabetes and ED should be further investigated for hypogonadism. The Androgen Deficiency in Aging Males (ADAM) instrument is the most widely accepted screening questionnaire, and, while bioavailable testosterone is recognized as the gold standard for biochemistry confirmation, total testosterone is an acceptable alternative if bioavailable testosterone is unavailable or unaffordable (40).

Treatment

While no randomized clinical trials have demonstrated that interventions that improve glycemic control also reduce the incidence and progression of ED, the Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS) showed that intensive glycemic control was effective for primary prevention of and secondary intervention for neuropathy, a condition that can impair sensory feedback from the penis, leading to reduced erectile function (41–43). The current data are controversial as it relates to diet, glycemic control and ED, with both positive and negative studies (28,44–46). Based on these conflicting data, a prudent physician should encourage tight glycemic control as a potential factor in maintaining erectile function (28).

The current mainstay of treatment for ED is therapy with PDE5 inhibitors. They have been reported to have a major impact on erectile function and quality of life, and should be offered as first-line therapy to men with diabetes wishing treatment for ED (47–52). Evidence for scheduled daily therapy is effective within the population with diabetes and ED (53,54), and may improve efficacy with lower rates of side effects, may impact lower urinary tract symptoms and has the potential for endothelial benefits (55). Additionally, among PDE5 inhibitor failure patients, use of a vacuum constriction device may salvage a significant percentage of erectile function and should be considered (56).

Contraindications for the use of PDE5 inhibitors include unstable angina or untreated cardiac ischemia and concomitant use of nitrates (3,57,58). Interestingly, men with diabetes appear to have lower rates of side effects with PDE5 inhibitors than the general population. This is believed to be a result of altered vasomotor tone or other factors (59).

Referral to a specialist in ED should be offered to men who do not respond to PDE5 inhibitors or for whom the use of PDE5 inhibitors is contraindicated. Second-line therapies (e.g. vacuum constriction devices, intracorporal injection therapy with prostaglandin E1 [PGE1] alone or in combination with papaverine and phentolamine [triple therapy], or intraurethral therapy using PGE1) or third-line therapy (penile prosthesis) may be considered for these men (60).

Ejaculatory Disorders

Ejaculatory disorders are a common disorder of sexual function in men with diabetes, occurring in 32–67% of that population (61). They range in scope from retrograde ejaculation, usually secondary to autonomic neuropathy with incomplete closure of the bladder neck during ejaculation, to premature or retarded ejaculation. Their recognition as an important component in sexual quality of life makes inquiry about ejaculatory function important.

Recommendations

  1. 1.All adult men with diabetes should be regularly screened for ED with a sexual function history [Grade D, Consensus].
  2. 2.Men with diabetes and ED should be investigated for hypogonadism [Grade D, Level 4 (16,31,32,34)].
  3. 3.A PDE5 inhibitor, if there are no contraindications to its use, should be offered as first-line therapy to men with diabetes and ED in either an on-demand [Grade A, Level 1A (47-53)] or scheduled-use [Grade B, Level 2 (53,54)] dosing regimen.
  4. 4.Referral to a specialist in ED should be considered for eugonadal men who do not respond to PDE5 inhibitors or for whom the use of PDE5 inhibitors is contraindicated [Grade D, Consensus].
  5. 5.Men with diabetes and ejaculatory dysfunction who are interested in fertility should be referred to a healthcare professional experienced in the treatment of ejaculatory dysfunction [Grade D, Consensus].

Abbreviations:
ED, erectile dysfunction; PDE5, phosphodiesterase type 5.

References

  1. 1 I. Eardley W. Fisher R.C. Rosen The multinational Men's Attitudes to Life Events and Sexuality study: the influence of diabetes on self-reported erectile function, attitudes and treatment-seeking patterns in men with erectile dysfunction Int J Clin Pract 61 2007 1446 1453
  2. 2 A. Al-Hunayan M. Al-Mutar E.O. Kehinde The prevalence and predictors of erectile dysfunction in men with newly diagnosed with type 2 diabetes mellitus BJU Int 99 2007 130 134
  3. 3 A. Aversa R. Bruzziches C. Vitale Chronic sildenafil in men with diabetes and erectile dysfunction Expert Opin Drug Metab Toxicol 3 2007 451 464
  4. 4 K.K. Chew C.M. Earle B.G. Stuckey Erectile dysfunction in general medicine practice: prevalence and clinical correlates Int J Impot Res 12 2000 41 45
  5. 5 T.J. Maatman D.K. Montague L.M. Martin Erectile dysfunction in men with diabetes mellitus Urology 29 1987 589 592
  6. 6 A. Rubin D. Babbott Impotence and diabetes mellitus JAMA 168 1958 498 500
  7. 7 R.C. Kolodny C.B. Kahn H.H. Goldstein Sexual dysfunction in diabetic men Diabetes 23 1974 306 309
  8. 8 D.K. McCulloch I.W. Campbell F.C. Wu The prevalence of diabetic impotence Diabetologia 18 1980 279 283
  9. 9 P. Zemel Sexual dysfunction in the diabetic patient with hypertension Am J Cardiol 61 1988 27H 33H
  10. 10 D.K. McCulloch R.J. Young R.J. Prescott The natural history of impotence in diabetic men Diabetologia 26 1984 437 440
  11. 11 C.G. Bacon F.B. Hu E. Giovannucci Association of type and duration of diabetes with erectile dysfunction in a large cohort of men Diabetes Care 25 2002 1458 1463
  12. 12 G. De Berardis F. Pellegrini M. Franciosi Identifying patients with type 2 diabetes with a higher likelihood of erectile dysfunction: the role of the interaction between clinical and psychological factors J Urol 169 2003 1422 1428
  13. 13 J. Angulo P. Cuevas A. Fernández Enhanced thromboxane receptor-mediated responses and impaired endothelium-dependent relaxation in human corpus cavernosum from diabetic impotent men: role of protein kinase C activity J Pharmacol Exp Ther 319 2006 783 789
  14. 14 J. Angulo C. Peiró P. Cuevas The novel antioxidant, AC3056 (2,6-di-t-butyl-4-((dimethyl-4-methoxyphenylsilyl) methyloxy)phenol), reverses erectile dysfunction in diabetic rats and improves NO-mediated responses in penile tissue from diabetic men J Sex Med 6 2009 373 387
  15. 15 J. Angulo R. González-Corrochano P. Cuevas Diabetes exacerbates the functional deficiency of NO/cGMP pathway associated with erectile dysfunction in human corpus cavernosum and penile arteries J Sex Med 7 2 pt 1 2010 758 768
  16. 16 O. Alexopoulou J. Jamart D. Maiter Erectile dysfunction and lower androgenicity in type 1 diabetic patients Diabetes Metab 27 2001 329 336
  17. 17 B.D. Naliboff M. Rosenthal Effects of age on complications in adult onset diabetes J Am Geriatr Soc 37 1989 838 842
  18. 18 H.A. Feldman I. Goldstein D.G. Hatzichristou Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study J Urol 151 1994 54 61
  19. 19 S.A. Grover I. Lowensteyn M. Kaouache The prevalence of erectile dysfunction in the primary care setting: importance of risk factors for diabetes and vascular disease Arch Intern Med 166 2006 213 219
  20. 20 E. Barrett-Connor Cardiovascular risk stratification and cardiovascular risk factors associated with erectile dysfunction: assessing cardiovascular risk in men with erectile dysfunction Clin Cardiol 27 suppl 1 2004 I8 I13
  21. 21 K.L. Billups Erectile dysfunction as an early sign of cardiovascular disease Int J Impot Res 17 suppl 1 2005 S19 S24
  22. 22 I.M. Thompson C.M. Tangen P.J. Goodman Erectile dysfunction and subsequent cardiovascular disease JAMA 294 2005 2996 3002
  23. 23 C. Gazzaruso Erectile dysfunction and coronary atherothrombosis in diabetic patients: pathophysiology, clinical features and treatment Expert Rev Cardiovasc Ther 4 2006 173 180
  24. 24 E. Barrett-Connor Heart disease risk factors predict erectile dysfunction 25 years later (the Rancho Bernardo Study) Am J Cardiol 96 2005 3M 7M
  25. 25 J.K. Min K.A. Williams T.M. Okwuosa Prediction of coronary heart disease by erectile dysfunction in men referred for nuclear stress testing Arch Intern Med 166 2006 201 206
  26. 26 E. Chiurlia R. D'Amico C. Ratti Subclinical coronary artery atherosclerosis in patients with erectile dysfunction J Am Coll Cardiol 46 2005 1503 1506
  27. 27 A.B. Araujo T.G. Travison P. Ganz Erectile dysfunction and mortality J Sex Med 6 2009 2445 2454
  28. 28 F. Giugliano M.I. Maiorino G. Bellastella Adherence to Mediterranean diet and erectile dysfunction in men with type 2 diabetes J Sex Med 7 2010 1911 1917
  29. 29 R. Klein B.E.K. Klein K.E. Lee Prevalence of self-reported erectile dysfunction in people with long-term IDDM Diabetes Care 19 1996 135 141
  30. 30 P.S. Grant D. Lipscomb How often do we ask about erectile dysfunction in the diabetes review clinic? Development of a neuropathy screening tool Acta Diabetol 46 2009 285 290
  31. 31 S. Dhindsa S. Prabhakar M. Sethi Frequent occurrence of hypogonadotropichypogonadism in type 2 diabetes J Clin Endocrinol Metab 89 2004 5462 5468
  32. 32 M.A. Boyanov Z. Boneva V.G. Christov Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency Aging Male 6 2003 1 7
  33. 33 R. Shabsigh J. Rajfer A. Aversa The evolving role of testosterone in the treatment of erectile dysfunction Int J Clin Pract 60 2006 1087 1092
  34. 34 R. Shabsigh J.M. Kaufman C. Steidle Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone J Urol 172 2004 658 663
  35. 35 A.I. El-Sakka H.M. Sayed K.A. Tayeb Androgen pattern in patients with type 2 diabetes-associated erectile dysfunction: impact of metabolic control Urology 74 2009 552 559
  36. 36 S.Y. Kalinchenko G.I. Kozlov N.P. Gontcharov Oral testosterone undecanoate reverses erectile dysfunction associated with diabetes mellitus in patients failing on sildenafil citrate therapy alone Aging Male 6 2003 94 99
  37. 37 R.C. Rosen A. Riley G. Wagner The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction Urology 49 1997 822 830
  38. 38 J.C. Cappelleri R.C. Rosen M.D. Smith Diagnostic evaluation of the erectile function domain of the International Index of Erectile Function Urology 54 1999 346 351
  39. 39 R. Ramanathan J. Mulhall S. Rao Prospective correlation between the International Index of Erectile Function (IIEF) and Sexual Health Inventory for Men (SHIM): implications for calculating a derived SHIM for clinical use J Sex Med 4 2007 1334 1344
  40. 40 A. Morales A. Bella S. Chun A practical guide to diagnosis, management and treatment of testosterone deficiency for Canadian physicians Can Urol Assoc J 4 2010 269 275
  41. 41 L. Valiquette F. Montorsi S. Auerbach Vardenafil Study Group. First-dose success with vardenafil in men with erectile dysfunction and associated comorbidities: RELY-I Int J Clin Pract 60 2006 1378 1385
  42. 42 The Diabetes Control and Complications Trial Research Group The effect of intensive diabetes therapy on the development and progression of neuropathy Ann Intern Med 122 1995 561 568
  43. 43 The Diabetes Control and Complications Trial Research Group The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus N Engl J Med 329 1993 977 986
  44. 44 UK Prospective Diabetes Study (UKPDS) Group Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33) Lancet 352 1998 837 853
  45. 45 N. Azad N.V. Emanuele C. Abraira The effects of intensive glycemic control on neuropathy in the VA Cooperative Study on Type II Diabetes Mellitus (VA CSDM) J Diabetes Complications 13 1990 307 313
  46. 46 A.I. El-Sakka H.M. Hassoba H.M. Sayed Pattern of endocrinal changes in patients with sexual dysfunction J Sex Med 2 2005 551 558
  47. 47 V. Fonseca A. Seftel J. Denne Impact of diabetes mellitus on the severity of erectile dysfunction and response to treatment: analysis of data from tadalafil clinical trials Diabetologia 47 2004 1914 1923
  48. 48 M.S. Rendell J. Rajfer P.A. Wicker Sildenafil for treatment of erectile dysfunction in men with diabetes: a randomized controlled trial JAMA 281 1999 421 426
  49. 49 A.J.M. Boulton J.-L. Selam M. Sweeney Sildenafil citrate for the treatment of erectile dysfunction in men with type II diabetes mellitus Diabetologia 44 2001 1296 1301
  50. 50 I. Goldstein J.M. Young J. Fischer Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes: a multicenter double-blind placebo-controlled fixed-dose study Diabetes Care 26 2003 777 783
  51. 51 I. Sáenz de Tejada G. Anglin J.R. Knight Effects of tadalafil on erectile dysfunction in men with diabetes Diabetes Care 25 2002 2159 2164
  52. 52 C.C. Carson T.F. Lue Phosphodiesterase type 5 inhibitors for erectile dysfunction BJU Int 96 2005 257 280
  53. 53 D. Hatzichristou M. Gambla E. Rubio-Aurioles Efficacy of tadalafil once daily in men with diabetes mellitus and erectile dysfunction Diabet Med 25 2008 138 146
  54. 54 J. Buvat Hermann Efficacy and safety of two dosing regimens of tadalafil and patterns of sexual activity in men with diabetes mellitus and erectile dysfunction: Scheduled Use vs. On-Demand Regimen Evaluation (SURE) study in 14 European countries J Sex Med 3 2006 512 520
  55. 55 A. Konstantinopoulos K. Giannitsas A. Athanasopoulos The impact of daily sildenafil on levels of soluble molecular markers of endothelial function in plasma in patients with erectile dysfunction Expert Opin Pharmacother 10 2009 155 160
  56. 56 O. Canguven J. Bailen W. Fredriksson Combination of vacuum erection device and PDE5 inhibitors as salvage therapy in PDE5 inhibitor nonresponders with erectile dysfunction J Sex Med 6 2009 2561 2567
  57. 57 A. Briganti A. Salonia A. Gallina Drug insight: oral phosphodiesterase type 5 inhibitors for erectile dysfunction Nat Clin Pract Urol 2 2005 239 247
  58. 58 R. DeBusk Y. Drory I. Goldstein Management of sexual dysfunction in patients with cardiovascular disease: recommendations of the Princeton Consensus Panel Am J Cardiol 86 2000 175 181
  59. 59 G. Brock S. Glina I. Moncada Likelihood of tadalafil-associated adverse events in integrated multiclinical trial database: classification tree analysis in men with erectile dysfunction Urology 73 2009 756 761
  60. 60 C.C. Carson J.J. Mulcahy F.E. Govier Efficacy, safety and patient satisfaction outcomes of the AMS 700CX inflatable penile prosthesis: results of a long-term multicenter study J Urol 164 2000 376 380
  61. 61 M.L. Isidro Sexual dysfunction in men with type 2 diabetes Postgrad Med 88 2012 152 159
 
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