Erectile dysfunction as a manifestation of urogenital autonomic neuropathy in patients with type 1 diabetes: epidemiology, classification, pathophysiology, diagnosis and treatment options
https://doi.org/10.14341/DM20142126-132
Abstract
Sexual dysfunction characterized by a significant decline in the quality of life of patients and leading to infertility and problems in social life is diagnosed in more than 40% of patients with diabetes mellitus (DM).
Erectile dysfunction is the most common sexual disorder in DM patients. The article describes epidemiology, classification, pathophysiology, diagnostic and treatment of erectile dysfunction in T1DM patients.
Erectile dysfunction is the most common sexual disorder in DM patients. The article describes epidemiology, classification, pathophysiology, diagnostic and treatment of erectile dysfunction in T1DM patients.
About the Authors
Gagik Radikovich Galstyan
Endocrinology Research Centre, Moscow
Russian Federation
MD, PhD, Professor, Head of the Diabetic Foot Department
Russian Federation
MD, PhD, Professor, Head of the Diabetic Foot Department
Yana Grigor'evna Shwarts
Endocrinology Research Centre, Moscow
Russian Federation
Postgraduate student of the Andrology and Urology department
Russian Federation
Postgraduate student of the Andrology and Urology department
Sergey Anatol'evich Dubsky
Endocrinology Research Centre, Moscow
Russian Federation
MD, PhD, Andrology and Urology department
Russian Federation
MD, PhD, Andrology and Urology department
Alexander Evgen'evich Lepetukhin
Endocrinology Research Centre, Moscow
Russian Federation
MD, PhD, Andrology and Urology department
Russian Federation
MD, PhD, Andrology and Urology department
Roman Viktorovich Rozhivanov
Endocrinology Research Centre, Moscow
Russian Federation
Competing Interests: MD, PhD, Senior Researcher of the Andrology and Urology department
Russian Federation
Competing Interests: MD, PhD, Senior Researcher of the Andrology and Urology department
Dmitry Gennadievich Kurbatov
Endocrinology Research Centre, Moscow
Russian Federation
MD, PhD, Professor, Head of the Andrology and Urology department
Russian Federation
MD, PhD, Professor, Head of the Andrology and Urology department
References
1. International Diabetes Federation. 2013. Available from: http://www.idf.org/worlddiabetesday/toolkit/gp/facts-figures/
2. Berrada S, Kadri N, Mechakra-Tahiri S, Nejjari C. Prevalence of erectile dysfunction and its correlates: a population-based study in Morocco. Int J Impot Res 2003;15 Suppl 1:1-3. Available from: http://www.nlm.nih.gov/medlineplus/erectiledysfunction.html PubMed PMID: 12825102. doi: 10.1038/sj.ijir.3900968.
3. Mak R, Backer GD, Kornitzer M, De Meyer JM. Prevalence and Correlates of Erectile Dysfunction in a Population-based Study in Belgium. European Urology 2002;41(2):132-138. Available from: http://linkinghub.elsevier.com/retrieve/pii/S030228380100029X doi: 10.1016/S0302-2838(01)00029-X.
4. Роживанов РВ, Сунцов ЮИ, Курбатов ДГ. Эректильная дисфункция у больных сахарным диабетом по данным контрольно-эпидемиологических исследований. Сахарный диабет. 2009;2: 51-54.[Rozhivanov RV, Suntsov YI, Kurbatov DG. Erectile dysfunction in patients with diabetes mellitus: results of epidemiological monitoring. Diabetes mellitus 2009; (2):51-54.] Available from: http://endojournals.ru/index.php/dia/article/view/5398 doi: 10.14341/2072-0351-5398.
5. Bancroft J, Gutierrez P. Erectile Dysfunction in Men With and Without Diabetes Mellitus: a Comparative Study. Diabet. Med 1996;13(1):84-89. Available from: http://doi.wiley.com/10.1002/%28SICI%291096-9136%28199601%2913%3A1%3C84%3A%3AAID-DIA16%3E3.3.CO%3B2-1 PubMed PMID: 8741818. doi: 10.1002/(SICI)1096-9136(199601)13:13.3.CO;2-1.
6. Schiel R, Müller UA. Prevalence of sexual disorders in a selection-free diabetic population (JEVIN. Diabetes Research and Clinical Practice 1999;44(2):115-121. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0168822799000121 doi: 10.1016/S0168-8227(99)00012-1.
7. Vinik A, Richardson D. Erectile dysfunction in diabetes. Diabetes Rev 1998;6(1):16-33.
8. Romeo JH, Seftel AD, Madhun ZT, Aron DC. Sexual function in men with diabetes type 2: association with glycemic control.. The Journal of Urology 2000;163(3):788-791. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0022534705678056 PubMed PMID: 10687978. doi: 10.1016/S0022-5347(05)67805-6.
9. Shiri R, Koskimäki J, Hakama M, Häkkinen J, Tammela TLJ, Huhtala H, et al. Effect of chronic diseases on incidence of erectile dysfunction. Urology 2003;62(6):1097-1102. Available from: http://www.nlm.nih.gov/medlineplus/copingwithchronicillness.html PubMed PMID: 14665363.
10. Seyoum B. Impotence in Ethiopian diabetic men. East Afr Med J 1998;75(4):208-210. Available from: http://www.nlm.nih.gov/medlineplus/diabetestype1.html PubMed PMID: 9745835.
11. Han PY, Ezquerro R, Pan K, Hwang S, Chung Y, Lu J. Comorbidities Associated with Diabetic Foot Complications Among Asian Americans in Southern California. Journal of the American Podiatric Medical Association 2003;93(1):37-41. Available from: http://www.japmaonline.org/doi/abs/10.7547/87507315-93-1-37 PubMed PMID: 12533555. doi: 10.7547/87507315-93-1-37.
12. Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic autonomic neuropathy. Diabetes Care 2003;26(5):1553-1579. Available from: http://www.scholaruniverse.com/ncbi-linkout?id=12716821 PubMed PMID: 12716821.
13. Роживанов РВ. Эректильная дисфункция у больных сахарным диабетом: скрининг, структура, прогностическое значение. Автореф. дисс…канд. мед. наук. М; 2005. 120с.[Rozhivanov RV. Erektil'naya disfunktsiya u bol'nykh sakharnym diabetom: skrining, struktura, prognosticheskoe znachenie.[dissertation]. Moscow; 2005.120p.]
14. Nusbaum MR. Erectile dysfunction: prevalence, etiology, and major risk factors.J. J Am Osteopath Assoc 2002;102(12 Suppl 4):1-6.
15. Rajfer J, Aronson WJ, Bush PA, Dorey FJ, Ignarro LJ. Nitric Oxide as a Mediator of Relaxation of the Corpus Cavernosum in Response to Nonadrenergic, Noncholinergic Neurotransmission. N Engl J Med 1992;326(2):90-94. Available from: http://www.nejm.org/doi/abs/10.1056/NEJM199201093260203 doi: 10.1056/NEJM199201093260203.
16. Gonzalez CM, Brannigan RE, Bervig T, Zelner D, Podlasek CA, McKenna KE, et al. Protein and gene expression of nitric oxide synthase isoforms I and III in the rat penile shaft. J Androl 2001;22:54-61.
17. Sullivan ME, Keoghane SR, Miller MAW. Vascular risk factors and erectile dysfunction. BJU International 2002;87(9):838-845. Available from: http://doi.wiley.com/10.1046/j.1464-410x.2001.02211.x doi: 10.1046/j.1464-410x.2001.02211.x.
18. Sullivan M. Nitric oxide and penile erection: Is erectile dysfunction another manifestation of vascular disease. Cardiovascular Research 1999;43(3):658-665. Available from: http://cardiovascres.oxfordjournals.org/cgi/doi/10.1016/S0008-6363(99)00135-2 doi: 10.1016/S0008-6363(99)00135-2.
19. Cartledge JJ, Eardley I, Morrison JFB. Impairment of corpus cavernosal smooth muscle relaxation by glycosylated human haemoglobin. BJU International 2001;85(6):735-741. Available from: http://doi.wiley.com/10.1046/j.1464-410x.2000.00599.x doi: 10.1046/j.1464-410x.2000.00599.x.
20. Cartledge JJ, Eardley I, Morrison JF. Advanced glycation end-products are responsible for the impairment of corpus cavemosal smooth muscle relaxation seen in diabetes. BrJUrol Int 2001;87(4):402-407.
21. Ferrara N. Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocrine Reviews 1992;13(1):18-32. Available from: http://edrv.endojournals.org/cgi/doi/10.1210/er.13.1.18 PubMed PMID: 1372863. doi: 10.1210/er.13.1.18.
22. Hirata C, Nakano K, Nakamura N, Kitagawa Y, Shigeta H, Hasegawa G, et al. Advanced Glycation End Products Induce Expression of Vascular Endothelial Growth Factor by Retinal Müller Cells. Biochemical and Biophysical Research Communications 1997;236(3):712-715. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0006291X97970364 doi: 10.1006/bbrc.1997.7036.
23. Sármán B, Tóth M, Somogyi A. Role of endothelin-1 in diabetes mellitus. Diabetes Metab. Rev 1998;14(2):171-175. Available from: http://doi.wiley.com/10.1002/%28SICI%291099-0895%28199806%2914%3A2%3C171%3A%3AAID-DMR207%3E3.0.CO%3B2-G doi: 10.1002/(SICI)1099-0895(199806)14:23.0.CO;2-G.
24. Marfella R, Quagliaro L, Nappo F, Ceriello A, Giugliano D. Acute hyperglycemia induces an oxidative stress in healthy subjects. J. Clin. Invest 2001;108(4):635-636. Available from: http://www.jci.org/articles/view/13727 doi: 10.1172/JCI13727.
25. Marfella R, Nappo F, De Angelis L, Paolisso G, Tagliamonte MR, Giugliano D. Hemodynamic effects of acute hyperglycemia in type 2 diabetic patients. Diabetes Care 2000;23(5):658-663. Available from: http://care.diabetesjournals.org/cgi/doi/10.2337/diacare.23.5.658 PubMed PMID: 10834426. doi: 10.2337/diacare.23.5.658.
26. Retter AS. Carnitine and its role in cardiovascular disease. Heart Dis 1999;1(12):108-113.
27. Lincoln J, Crowe R, Blacklay PF, Pryor JP, Lumley JS, Burnstock G. Changes in the VIPergic, cholinergic and adrenergic innervation of human penile tissue in diabetic and non-diabetic impotent males. J Urol 1987;137(5):1053-1059. Available from: http://www.scholaruniverse.com/ncbi-linkout?id=2437329 PubMed PMID: 2437329.
28. Hecht MJ, Neundörfer B, Kiesewetter F, Hilz MJ. Neuropathy is a major contributing factor to diabetic erectile dysfunction. Neurological Research 2001;23(6):651-654. Available from: http://www.maneyonline.com/doi/abs/10.1179/016164101101198965 doi: 10.1179/016164101101198965.
29. Harati Y. Diabetes and the nervous system. Endocrinology and Metabolism Clinics of North America 1996;25(2):325-359. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0889852905703273 PubMed PMID: 8799703. doi: 10.1016/S0889-8529(05)70327-3.
30. Veves A, Webster L, Chen TF, Payne S, Boulton AJM. Aetiopathogenesis and Management of Impotence in Diabetic Males: Four Years Experience from a Combined Clinic. Diabetic Medicine 1995;12(1):77-82. Available from: http://doi.wiley.com/10.1111/j.1464-5491.1995.tb02067.x doi: 10.1111/j.1464-5491.1995.tb02067.x.
31. Hakim LS, Goldstein I. Diabetic sexual dysfunction. Endocrinology and Metabolism Clinics of North America 1996;25(2):379-400. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0889852905703297 doi: 10.1016/S0889-8529(05)70329-7.
32. Stevens M.J, Feldman E.L, Greene D.A. Diabetic peripheral neuropathy. Current therapy of diabetes mellitus. Eds. R. A. Defronzo. St. Louis: Mosby. 1998:160-165.
33. Балаболкин МИ, Клебанова ЕМ, Креминская ВМ. Патогенез ангиопатий при сахарном диабете. Сахарный диабет. 1999;1: 2-9.[Balabolkin MI, Klebanova EM, Kreminskaya VM. Patogenez angiopatiy pri sakharnom diabete. Diabetes mellitus. 1999;(1):2-8.] Available from: http://endojournals.ru/index.php/dia/article/view/5725 doi: 10.14341/2072-0351-5725.
34. Калинченко CЮ, Роживанов РВ. Нейрогенные нарушения половой функции у мужчин, страдающих сахарным диабетом. Врач. 2006;(1): 48-51. [Kalinchenko CYu, Rozhivanov RV. Neyrogennye narusheniya polovoy funktsii u muzhchin, stradayushchikh sakharnym diabetom. Vrach. 2006;(1): 48-51.]
35. Курбатов ДГ, Роживанов РВ, Приймак ДВ. Эректильная дисфункция у больных сахарным диабетом. Русский медицинский журнал. 2009; 17(25): 1672-1676. [Kurbatov DG, Rozhivanov RV, Priymak DV. Erektil'naya disfunktsiya u bol'nykh sakharnym diabetom.Russkii meditsinskii zhurnal. 2009; 17(25):1672-1676.]
36. Rossi P, Menchini Fabris F , Fiorini I, Palego P, Simi S, Rossi B, et al. Comparison between plasma concentrations of testosterone, nitric oxide and endothelin 1–2 in penile and brachial venous blood: preliminary results in men with psychogenic impotence. Biomedicine & Pharmacotherapy 1998;52(7-8):308-310. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0753332298800267 PubMed PMID: 9809174. doi: 10.1016/S0753-3322(98)80026-7.
37. Schirar A, Chang C, Rousseau JP. Localization of Androgen Receptor in Nitric Oxide Synthase- and Vasoactive Intestinal Peptide-Containing Neurons of the Major Pelvic Ganglion Innervating the Rat Penis. Journal of Neuroendocrinology 2003;9(2):141-150. Available from: http://doi.wiley.com/10.1046/j.1365-2826.1997.00557.x doi: 10.1046/j.1365-2826.1997.00557.x.
38. Schiavi RC, White D, Mandeli J, Schreiner-Engel P. Hormones and nocturnal penile tumescence in healthy aging men. Arch Sex Behav 1993;22(3):207-215. Available from: http://link.springer.com/10.1007/BF01541766 doi: 10.1007/BF01541766.
39. Alexopoulou O, Jamart J, Maiter D, Hermans MP, De Hertogh R, De Nayer P, et al. Erectile dysfunction and lower androgenicity in type 1 diabetic patients.. Diabetes Metab 2001;27(3):329-336. Available from: http://www.masson.fr/masson/MDOI-DM-06-2001-27-3-1262-3636-101019-ART4 PubMed PMID: 11431598.
40. Cunningham MJ. Leptin's Actions on the Reproductive Axis: Perspectives and Mechanisms. Biology of Reproduction 1999;60(2):216-222. Available from: http://www.biolreprod.org/cgi/doi/10.1095/biolreprod60.2.216 doi: 10.1095/biolreprod60.2.216.
41. Лоран ОБ, Щеплев ПА, Нестеров СН, Кухаркин СА. Современные методы диагностики и лечения эректильных дисфункций. Русский медицинский журнал. 2000; 8 (3): 130–134.[Loran OB, Shcheplev PA, Nesterov SN, Kukharkin SA. Sovremennye metody diagnostiki i lecheniya erektil'nykh disfunktsiy. Russkii meditsinskii zhurnal. 2000; 8 (3): 130–134.]
42. Дедов ИИ, Шестакова МВ, Максимова МА. Федеральная целевая программа «Сахарный диабет». Методические рекомендации. Москва; 2002. [Dedov II, Shestakova MV, Maksimova MA. Federal'naya tselevaya programma «Sakharnyy diabet». Metodicheskie rekomendatsii. Moscow; 2002.]
43. Тиктинский ОЛ, Михайличенко ВВ. Андрология. Москва: Медиа Пресс; 1999. [Tiktinskiy OL, Mikhaylichenko VV. Andrologiya. Moscow:Media Press;1999.]
44. Роживанов РВ, Бондаренко ОН, Удовиченко ОВ, Калинченко СЮ, Сунцов ЮИ, Глебов СП. Физикальное неврологическое обследование как скрининг-метод диагностики нейрогенной эректильной дисфункции у больных сахарным диабетом. Врач. 2005; 5: 29-30.
45. Коган МИ, Калиниченко СЮ, Роживанов РВ. Нарушения половой функции у мужчин при сахарном диабете. Руководство для врачей. Под редакцией М.И. Когана. Москва; 2005. 218 с.[ Kogan MI, Kalinichenko SYu, Rozhivanov RV. Narusheniya polovoy funktsii u muzhchin pri sakharnom diabete. Rukovodstvo dlya vrachey. Ed. by M.I. Kogana. Moskva; 2005. 218 p.]
46. Мазо ЕБ, Дмитриев ДГ, Худолей ДЮ. Сравнительная оценка показателей электромиографии полового члена и данных микроскопии кавернозной ткани у больных с эректильной дисфукцией в диагностике кавернозной инервации. Андрология и генитальная хирургия. 2000; (1): 55–56.[Mazo EB, Dmitriev DG, Khudoley DYu. Sravnitel'naya otsenka pokazateley elektromiografii polovogo chlena i dannykh mikroskopii kavernoznoy tkani u bol'nykh s erektil'noy disfuktsiey v diagnostike kavernoznoy inervatsii. Andrologiya i genital'naya khirurgiya. 2000; (1): 55–56.]
47. Aggour A, Mostafa H, Еl-Shawaf H. Evaluation of the role of corpus cavernosum electromyography as a noninvasive diagnostic tool in male erectile dysfunction. Int Urol Nephrol 1998;30(1):75-79.
48. Зубарев АР, Митькова МД, Корякин МВ, Митьков ВВ. Ультразвуковая диагностика наружных половых органов у мужчин. Москва: Видар; 1999. [Zubarev AR, Mit'kova MD, Koryakin MV, Mit'kov VV. Ul'trazvukovaya diagnostika naruzhnykh polovykh organov u muzhchin. Moscow: Vidar; 1999.]
49. Курбатов ДГ, Роживанов РВ. Возможности терапии генитальной нейропатии ингибиторами фосфодиэстеразы 5 типа у больных сахарным диабетом. Урология. 2009;(5): 48-49. [Kurbatov DG, Rozhivanov RV. Vozmozhnosti terapii genital'noy neyropatii ingibitorami fosfodiesterazy 5 tipa u bol'nykh sakharnym diabetom. Urologiia. 2009;(5): 48-49.]
50. Рафальский ВВ. Подходы к рациональному выбору ингибиторов фосфодиэстеразы 5 типа. Фарматека. 2004; 96(19/20):64-71.[Rafal'skiy VV. Podkhody k ratsional'nomu vyboru ingibitorov fosfodiesterazy 5 tipa. Farmateka. 2004; 96(19/20):64-71]
51. Goldstein I, Young JM, Fischer J, Bangerter K, Segerson T, Taylor T. 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 2003;26(3):777-783. Available from: http://care.diabetesjournals.org/cgi/doi/10.2337/diacare.26.3.777 doi: 10.2337/diacare.26.3.777.
52. Fonseca V, Seftel A, Denne J, Fredlund P. Impact of diabetes mellitus on the severity of erectile dysfunction and response to treatment: analysis of data from tadalafil clinical trials. Diabetologia 2004;47(11):1914-1923. Available from: http://link.springer.com/10.1007/s00125-004-1549-6 PubMed PMID: 15599697. doi: 10.1007/s00125-004-1549-6.
53. Giuliano F, Varfnese L. Tadalafil: a novel treatment for erectile dysfunction. Eur. Heart. J. European Heart Journal Supplements 2002;4(suppl. H):24-31. Available from: http://eurheartjsupp.oxfordjournals.org/content/4/suppl_H/H24.full.pdf
54. Saenz de Tejada, I, , Anglin G, Knight JR, Emmick JT. Effects of Tadalafil on Erectile Dysfunction in Men With Diabetes. Diabetes Care 2002;25(12):2159-2164. Available from: http://care.diabetesjournals.org/cgi/doi/10.2337/diacare.25.12.2159 doi: 10.2337/diacare.25.12.2159.
55. Yassin A, Diede HE, Saad F, Traish A. . Combination therapy of Tadalafil &Testosterone in hypogonadal non-responders. International Journal of Impotence Research 2003;15(Suppl. 6):27.
56. Роживанов РВ, Курбатов ДГ. Особенности терапии эректильной дисфункции у пациентов с гипогонадизмом. Врач. 2009;(3): 65-69.[Rozhivanov RV, Kurbatov DG. Osobennosti terapii erektil'noy disfunktsii u patsientov s gipogonadizmom. Vrach. 2009;(3): 65-69.]
57. Роживанов РВ, Лепетухин АЕ, Дубский СА, Курбатов ДГ. Особенности коррекции сексуальной дисфункции у мужчин, больных сахарным диабетом. Сахарный диабет. 2010; 3: 30-31.
58. Hackett G. PDE5 inhibitors in diabetic peripheral neuropathy. International Journal of Clinical Practice 2006;60(9):1123-1126. Available from: http://doi.wiley.com/10.1111/j.1742-1241.2006.01087.x PubMed PMID: 16939556. doi: 10.1111/j.1742-1241.2006.01087.x.
59. Ziegler D. Clinical aspects, diagnosis and therapy of diabetic neuropathy. Ther Umsch 1996;53(12):948-957. Available from: http://www.scholaruniverse.com/ncbi-linkout?id=9036573 PubMed PMID: 9036573.
60. Mijnhout, GS, Alkhalaf A, Kleefstra N, Bilo H.J.G . Alpha lipoic acid: a new treatment forneuropathic pain in patients with diabetes. The Netherlands Journal of Medicine 2010;64(4):158-162.
Supplementary files
Review
For citations:
Galstyan G.R., Shwarts Ya.G., Dubsky S.A., Lepetukhin A.E., Rozhivanov R.V., Kurbatov D.G. Erectile dysfunction as a manifestation of urogenital autonomic neuropathy in patients with type 1 diabetes: epidemiology, classification, pathophysiology, diagnosis and treatment options. Diabetes mellitus. 2014;17(2):126-132. https://doi.org/10.14341/DM20142126-132
Views:
4771
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).
Email this article 
