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Current Sexual Health Reports

Erschienen in:

06.11.2019 | Female Sexual Dysfunction and Disorders (A Pastuszak and N Thirumavalavan, Section Editors)

The Complex Relationship Between Erectile Dysfunction and Hypogonadism in Diabetes Mellitus

verfasst von: Levi C. Holland, B.S., Jonathan A. Beilan, M.D., Alexander J. Tatem, M.D., Larry I. Lipshultz, M.D.

Erschienen in: Current Sexual Health Reports | Ausgabe 4/2019

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Abstract

Purpose of Review

As the prevalence of diabetes mellitus grows worldwide, it is increasingly important to understand the commonly comorbid urologic conditions, hypogonadism and erectile dysfunction, in the setting of the diabetic man. The relationship between the diabetes, hypogonadism, and erectile dysfunction is complex with significant interplay among the disease processes and potential for unique management of the triad. The purpose of this review is to provide an update on the intertwined nature of these diseases in diabetics with special consideration for pathophysiology, diagnosis, and management.

Recent Findings

There is a wide range of pathophysiologic mechanisms central to hypogonadism and erectile dysfunction in diabetes mellitus which continue to be identified and better elucidated; nevertheless, metabolic syndrome, composed of insulin resistance, dyslipidemia, hypertension, and obesity, appears to be the common thread between both. An increasing body of evidence suggests that low testosterone is an independent risk factor for cardiovascular disease and worsened overall survival in diabetic men with potential that testosterone therapy may reduce these risks. The treatment of either erectile dysfunction or hypogonadism in diabetic men may also improve the other condition; some evidence suggests that testosterone therapy in hypogonadal diabetics may improve erectile function while daily vardenafil, in addition to improving erectile function, appears to restore hypogonadal diabetics’ testosterone to the eugonadal range.

Summary

Metabolic syndrome appears to be the central connection between the increasingly common clinical picture of diabetic men with erectile dysfunction and hypogonadism. The overlapping pathophysiology of these conditions results in unique management considerations.

World Health Organization. Global Report on Diabetes. Geneva: WHO Press; 2016.

Kouidrat Y, Pizzol D, Cosco T, Thompson T, Carnaghi M, Bertoldo A, et al. High prevalence of erectile dysfunction in diabetes: a systematic review and meta-analysis of 145 studies. Diabet Med. 2017;34(9):1185–92. https://doi.org/10.1111/dme.13403.CrossRefPubMed

Giuliano FA, Leriche A, Jaudinot EO, de Gendre AS. Prevalence of erectile dysfunction among 7689 patients with diabetes or hypertension, or both. Urology. 2004;64(6):1196–201. https://doi.org/10.1016/j.urology.2004.08.059.CrossRefPubMed

Selvin E, Burnett AL, Platz EA. Prevalence and risk factors for erectile dysfunction in the US. Am J Med. 2007;120(2):151–7. https://doi.org/10.1016/j.amjmed.2006.06.010.CrossRefPubMed

Dhindsa S, Prabhakar S, Sethi M, Bandyopadhyay A, Chaudhuri A, Dandona P. Frequent occurrence of hypogonadotropic hypogonadism in type 2 Diabetes. J Clin Endocrinol Metab. 2004;89(11):5462–8. https://doi.org/10.1210/jc.2004-0804.CrossRefPubMed

Corona G, Mannucci E, Petrone L, Ricca V, Balercia G, Mansani R, et al. Association of hypogonadism and type II diabetes in men attending an outpatient erectile dysfunction clinic. Int J Impot Res. 2006;18(2):190–7. https://doi.org/10.1038/sj.ijir.3901391.CrossRefPubMed

Hamilton EJ, Davis WA, Makepeace A, et al. Prevalence and prognosis of a low serum testosterone in men with type 2 diabetes: the Fremantle Diabetes Study Phase II. Clin Endocrinol. 2016;85(3):444–52. https://doi.org/10.1111/cen.13087.CrossRef

Grossmann M, Thomas MC, Panagiotopoulos S, Sharpe K, Macisaac RJ, Clarke S, et al. Low testosterone levels are common and associated with insulin resistance in men with diabetes. J Clin Endocrinol Metab. 2008;93(5):1834–40. https://doi.org/10.1210/jc.2007-2177.CrossRefPubMed

Chandel A, Dhindsa S, Topiwala S, Chaudhuri A, Dandona P. Testosterone concentration in young patients with Diabetes. Diabetes Care. 2008;31(10):2013–7. https://doi.org/10.2337/dc08-0851.CrossRefPubMedPubMedCentral

10.

Alberti KGMM, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640–5. https://doi.org/10.1161/CIRCULATIONAHA.109.192644.CrossRefPubMed

11.

Hadi HA, Carr CS, Al SJ. Endothelial dysfunction: cardiovascular risk factors, therapy, and outcome. Vasc Health Risk Manag. 2005;1(3):183–98.PubMedPubMedCentral

12.

Castela Â, Costa C. Molecular mechanisms associated with diabetic endothelial–erectile dysfunction. Nat Rev Urol. 2016;13(5):266–74. https://doi.org/10.1038/nrurol.2016.23.CrossRefPubMed

13.

Gandhi J, Dagur G, Warren K, et al. The role of diabetes mellitus in sexual and reproductive health: an overview of pathogenesis, evaluation, and management. Curr Diabetes Rev. 2017;13(6). https://doi.org/10.2174/1573399813666161122124017.

14.

Musicki B, Hannan JL, Lagoda G, Bivalacqua TJ, Burnett AL. Mechanistic link between erectile dysfunction and systemic endothelial dysfunction in type 2 diabetic rats. Andrology. 2016;4(5):977–83. https://doi.org/10.1111/andr.12218.CrossRefPubMedPubMedCentral

15.

Moore CR, Wang R. Pathophysiology and treatment of diabetic erectile dysfunction. Asian J Androl. 2006;8(6):675–84. https://doi.org/10.1111/j.1745-7262.2006.00223.x.CrossRefPubMed

16.

Dhindsa S, Ghanim H, Batra M, Dandona P. Hypogonadotropic hypogonadism in men with diabesity. Diabetes Care. 2018;41(7):1516–25. https://doi.org/10.2337/dc17-2510.CrossRefPubMedPubMedCentral

17.

Dhindsa S, Miller MG, McWhirter CL, Mager DE, Ghanim H, Chaudhuri A, et al. Testosterone concentrations in diabetic and nondiabetic obese men. Diabetes Care. 2010;33(6):1186–92. https://doi.org/10.2337/dc09-1649.CrossRefPubMedPubMedCentral

18.

Saboor Aftab SA, Kumar S, Barber TM. The role of obesity and type 2 diabetes mellitus in the development of male obesity-associated secondary hypogonadism. Clin Endocrinol. 2013;78(3):330–7. https://doi.org/10.1111/cen.12092.CrossRef

19.

Pitteloud N, Hardin M, Dwyer AA, et al. Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men. J Clin Endocrinol Metab. 2005;90(5):2636–41. https://doi.org/10.1210/jc.2004-2190.CrossRefPubMed

20.

Traish A, Kim N. The physiological role of androgens in penile erection: regulation of corpus cavernosum structure and function. J Sex Med. 2005;2(6):759–70. https://doi.org/10.1111/j.1743-6109.2005.00094.x.CrossRefPubMed

21.

Burnett AL, Nehra A, Breau RH, Culkin DJ, Faraday MM, Hakim LS, et al. Erectile dysfunction: AUA guideline. J Urol. 2018;200(3):633–41. https://doi.org/10.1016/j.juro.2018.05.004.CrossRefPubMed

22.

• 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. https://doi.org/10.1111/dme.13553A meta-analysis of randomized controlled trials which shows that testosterone therapy may moderately improve erectile function and sexual desire in hypogonadal type 2 diabetics. CrossRefPubMed

23.

•• Santi D, Granata ARM, Guidi A, et al. 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. https://doi.org/10.1530/EJE-15-1100High-quality trial demonstrating that daily vardenafil improves inflammatory parameters in addition to hypogonadism. CrossRefPubMed

24.

Owiredu WKBA, Alidu H, Amidu N, Obirikorang C, Gyasi-Sarpong CK, Bawah AT, et al. Sexual dysfunction among diabetics and its impact on the SQoL of their partners. Int J Impot Res. 2017;29(6):250–7. https://doi.org/10.1038/ijir.2017.32.CrossRefPubMed

25.

Berardis GD, Franciosi M, Belfiglio M, et al. Erectile dysfunction and quality of life in type 2 Diabetic patients: a serious problem too often overlooked. Diabetes Care. 2002;25(2):284–91. https://doi.org/10.2337/diacare.25.2.284.CrossRefPubMed

26.

Malavige LS, Jayaratne SD, Kathriarachchi ST, Sivayogan S, Ranasinghe P, Levy JC. Erectile dysfunction is a strong predictor of poor quality of life in men with Type 2 diabetes mellitus. Diabet Med. 2014;31(6):699–706. https://doi.org/10.1111/dme.12412.CrossRefPubMed

27.

Chen S, Peng D, Xu X, Gao J, Dai F, Zuo C, et al. Assessment of erectile dysfunction and associated psychological distress in Chinese men with type 2 diabetes mellitus. Int J Impot Res. 2017;29(5):210–4. https://doi.org/10.1038/ijir.2017.25.CrossRefPubMed

28.

Furukawa S, Sakai T, Niiya T, Miyaoka H, Miyake T, Yamamoto S, et al. Depressive symptoms and prevalence of erectile dysfunction in Japanese patients with type 2 diabetes mellitus: the Dogo Study. Int J Impot Res. 2017;29(2):57–60. https://doi.org/10.1038/ijir.2016.45.CrossRefPubMed

29.

Maiorino MI, Bellastella G, Volpe ED, et al. Erectile dysfunction in young men with type 1 diabetes. Int J Impot Res. 2017;29(1):17–22. https://doi.org/10.1038/ijir.2016.38.CrossRefPubMed

30.

Batty GD, Li Q, Czernichow S, Neal B, Zoungas S, Huxley R, et al. Erectile dysfunction and later cardiovascular disease in men with type 2 diabetes: prospective cohort study based on the ADVANCE trial. J Am Coll Cardiol. 2010;56(23):1908–13. https://doi.org/10.1016/j.jacc.2010.04.067.CrossRefPubMedPubMedCentral

31.

Gandaglia G, Briganti A, Jackson G, Kloner RA, Montorsi F, Montorsi P, et al. A systematic review of the association between erectile dysfunction and cardiovascular disease. Eur Urol. 2014;65(5):968–78. https://doi.org/10.1016/j.eururo.2013.08.023.CrossRefPubMed

32.

Yao F-J, Zhang Y-D, Wan Z, Li W, Lin H, Deng CH, et al. Erectile dysfunction is associated with subclinical carotid vascular disease in young men lacking widely-known risk factors. Asian J Androl. 2018;20(4):400–4. https://doi.org/10.4103/aja.aja_73_17.CrossRefPubMedPubMedCentral

33.

Banks E, Joshy G, Abhayaratna WP, et al. Erectile dysfunction severity as a risk marker for cardiovascular disease hospitalisation and all-cause mortality: a prospective cohort study. PLoS Med. 2013;10(1):e1001372. https://doi.org/10.1371/journal.pmed.1001372.CrossRefPubMedPubMedCentral

34.

Thorve VS, Kshirsagar AD, Vyawahare NS, Joshi VS, Ingale KG, Mohite RJ. Diabetes-induced erectile dysfunction: epidemiology, pathophysiology and management. J Diabetes Complicat. 2011;25(2):129–36. https://doi.org/10.1016/j.jdiacomp.2010.03.003.CrossRefPubMed

35.

Ben Khedher MR, Abid M, Jamoussi K, Hammami M. Comprehensive insight into functional interaction between GNB3 C825T and eNOS T-786C, G894T gene polymorphisms and association with susceptibility to diabetic erectile dysfunction. Andrology. 2018. https://doi.org/10.1111/andr.12543.

36.

Castela A, Gomes P, Domingues VF, Paíga P, Costa R, Vendeira P, et al. Role of oxidative stress-induced systemic and cavernosal molecular alterations in the progression of diabetic erectile dysfunction. J Diabetes. 2015;7(3):393–401. https://doi.org/10.1111/1753-0407.12181.CrossRefPubMed

37.

Miao L, Dai Y, Zhang J. Mechanism of RhoA/Rho kinase activation in endothelin-1- induced contraction in rabbit basilar artery. Am J Physiol Heart Circ Physiol. 2002;283(3):H983–9. https://doi.org/10.1152/ajpheart.00141.2002.CrossRefPubMed

38.

Alves-Lopes R, Neves KB, Montezano AC, Harvey A, Carneiro FS, Touyz RM, et al. Internal pudental artery dysfunction in Diabetes mellitus is mediated by NOX1-Derived ROS-, Nrf2-, and rho kinase-dependent mechanisms. Hypertension. 2016;68(4):1056–64. https://doi.org/10.1161/HYPERTENSIONAHA.116.07518.CrossRefPubMed

39.

Takahashi K, Ghatei MA, Lam HC, O’Halloran DJ, Bloom SR. Elevated plasma endothelin in patients with diabetes mellitus. Diabetologia. 1990;33(5):306–10.CrossRef

40.

Alkan E, Ugan RA, Basar MM, et al. Role of endothelin receptors and relationship with nitric oxide synthase in impaired erectile response in diabetic rats. Andrologia. 2017;49(2). https://doi.org/10.1111/and.12607.

41.

Azmi S, Ferdousi M, Alam U, Petropoulos IN, Ponirakis G, Marshall A, et al. Small-fibre neuropathy in men with type 1 diabetes and erectile dysfunction: a cross-sectional study. Diabetologia. 2017;60(6):1094–101. https://doi.org/10.1007/s00125-017-4245-z.CrossRefPubMedPubMedCentral

42.

Furukawa S, Sakai T, Niiya T, Miyaoka H, Miyake T, Yamamoto S, et al. Diabetic peripheral neuropathy and prevalence of erectile dysfunction in Japanese patients aged <65 years with type 2 diabetes mellitus: The Dogo Study. Int J Impot Res. 2017;29(1):30–4. https://doi.org/10.1038/ijir.2016.40.CrossRefPubMed

43.

Malavige LS, Levy JC. Erectile dysfunction in Diabetes mellitus. J Sex Med. 2009;6(5):1232–47. https://doi.org/10.1111/j.1743-6109.2008.01168.x.CrossRefPubMed

44.

Matsui H, Musicki B, Sopko NA, et al. Early-stage type 2 diabetes mellitus impairs erectile function and neurite outgrowth from the major pelvic ganglion and downregulates the gene expression of neurotrophic factors. Urology. 2017;99:287.e1–7. https://doi.org/10.1016/j.urology.2016.08.045.CrossRef

45.

Hu L, Qi S, Zhang K, Fu Q. Essential role of brain-derived neurotrophic factor (bdnf) in diabetic erectile dysfunction. Andrologia. 2018;50(3). https://doi.org/10.1111/and.12924.

46.

Shan H, Chen F, Zhang T, He S, Xu L, Wei A. Stem cell therapy for erectile dysfunction of cavernous nerve injury rats: a systematic review and meta-analysis. PLoS ONE. 2015;10(4):e0121428. https://doi.org/10.1371/journal.pone.0121428.CrossRefPubMedPubMedCentral

47.

Aversa A, Isidori AM, De Martino MU, et al. Androgens and penile erection: evidence for a direct relationship between free testosterone and cavernous vasodilation in men with erectile dysfunction. Clin Endocrinol. 2000;53(4):517–22.CrossRef

48.

Yu J, Akishita M, Eto M, Ogawa S, Son BK, Kato S, et al. Androgen receptor-dependent activation of endothelial nitric oxide synthase in vascular endothelial cells: role of phosphatidylinositol 3-kinase/akt pathway. Endocrinology. 2010;151(4):1822–8. https://doi.org/10.1210/en.2009-1048.CrossRefPubMed

49.

Cui K, Li R, Liu K, Wang T, Liu J, Rao K. Testosterone preserves endothelial function through regulation of S1P1/Akt/FOXO3a signalling pathway in the rat corpus cavernosum. Andrologia. 2018:e13173. https://doi.org/10.1111/and.13173.

50.

Alves-Lopes RU, Neves KB, Silva MA, Olivon VC, Ruginsk SG, Antunes-Rodrigues J, et al. Functional and structural changes in internal pudendal arteries underlie erectile dysfunction induced by androgen deprivation. Asian J Androl. 2017;19(5):526–32. https://doi.org/10.4103/1008-682X.173935.CrossRefPubMed

51.

Yildiz O, Seyrek M, Irkilata HC, Yildirim I, Tahmaz L, Dayanc M. Testosterone might cause relaxation of human corpus cavernosum by potassium channel opening action. Urology. 2009;74(1):229–32. https://doi.org/10.1016/j.urology.2008.12.022.CrossRefPubMed

52.

Yamamoto H, Sasaki S, Tatsura H, Umemoto Y, Kubota H, Kamiya H, et al. Penile apoptosis in association with p53 under lack of testosterone. Urol Res. 2004;32(1):9–13. https://doi.org/10.1007/s00240-003-0358-6.CrossRefPubMed

53.

Traish AM, Toselli P, Jeong S-J, Kim NN. Adipocyte accumulation in penile corpus cavernosum of the orchiectomized rabbit: a potential mechanism for veno-occlusive dysfunction in androgen deficiency. J Androl. 2005;26(2):242–8.CrossRef

54.

Shen Z-J, Zhou X-L, Lu Y-L, Chen Z-D. Effect of androgen deprivation on penile ultrastructure. Asian J Androl. 2003;5(1):33–6.PubMed

55.

Traish AM, Munarriz R, O’Connell L, et al. Effects of medical or surgical castration on erectile function in an animal model. J Androl. 2003;24(3):381–7.CrossRef

56.

Corona G, Mannucci E, Mansani R, Petrone L, Bartolini M, Giommi R, et al. Organic, relational and psychological factors in erectile dysfunction in men with diabetes mellitus. Eur Urol. 2004;46(2):222–8. https://doi.org/10.1016/j.eururo.2004.03.010.CrossRefPubMed

57.

Bhasin S, Enzlin P, Coviello A, Basson R. Sexual dysfunction in men and women with endocrine disorders. Lancet Lond Engl. 2007;369(9561):597–611. https://doi.org/10.1016/S0140-6736(07)60280-3.CrossRef

58.

Zamorano-Leon JJ, Segura A, Lahera V, et al. Relationship between erectile dysfunction, diabetes and dyslipidemia in hypertensive-treated men. Urol J. 2018;15(6):370–5. https://doi.org/10.22037/uj.v0i0.4068.CrossRefPubMed

59.

Chen C, Zhai H, Huang G, Cheng J, Xia F, Zhao L, et al. Is lower low-density lipoprotein cholesterol associated with lower androgen and erectile dysfunction in men? Nutr Metab Cardiovasc Dis NMCD. 2018;28(12):1304–10. https://doi.org/10.1016/j.numecd.2018.08.006.CrossRefPubMed

60.

Cho JW, Duffy JF. Sleep, sleep disorders, and sexual dysfunction. World J Mens Health. 2018. https://doi.org/10.5534/wjmh.180045.

61.

Yang G, Muzepper M. Platelet indices and erectile dysfunction: a systematic review and meta-analysis. Andrologia. 2019;51(5):e13248. https://doi.org/10.1111/and.13248.CrossRefPubMed

62.

Tangal S, Ozayar A, Ener K, Gokçe MI, Haliloglu AH. Does mean platelet volume (MPV) have a role in evaluation of erectile dysfunction and its severity? Rev Int Androl. 2018. https://doi.org/10.1016/j.androl.2018.07.007.

63.

• El Taieb MA, Hegazy EM, Maklad SM, Khairy R. Platelet Indices as a marker for early prediction of erectile dysfunction in diabetic patients. Andrologia. 2019;51(1):e13163. https://doi.org/10.1111/and.13163Platelet indices may be used to predict diabetic vasculogenic ED.CrossRefPubMed

64.

• 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. 2018. https://doi.org/10.1007/s00345-018-2583-1On-demand vardenafil and mirodenafil may have higher efficacy with lower adverse events in diabetic men than other PDE5i's.

65.

Buvat J, Montorsi F, Maggi M, Porst H, Kaipia A, Colson MH, et al. Hypogonadal men nonresponders to the PDE5 inhibitor tadalafil benefit from normalization of testosterone levels with a 1% hydroalcoholic testosterone gel in the treatment of erectile dysfunction (TADTEST Study). J Sex Med. 2011;8(1):284–93. https://doi.org/10.1111/j.1743-6109.2010.01956.x.CrossRefPubMed

66.

Hackett G, Cole N, Bhartia M, et al. Testosterone replacement therapy improves metabolic parameters in hypogonadal men with type 2 diabetes but not in men with coexisting depression: the BLAST study. J Sex Med. 2014;11(3):840–56. https://doi.org/10.1111/jsm.12404.CrossRefPubMed

67.

Hackett G, Cole N, Bhartia M, Kennedy D, Raju J, Wilkinson P, et al. The response to testosterone undecanoate in men with type 2 diabetes is dependent on achieving threshold serum levels (the BLAST study). Int J Clin Pract. 2014;68(2):203–15. https://doi.org/10.1111/ijcp.12235.CrossRefPubMed

68.

Man L, Li G. Low-intensity extracorporeal shock wave therapy for erectile dysfunction: a systematic review and meta-analysis. Urology. 2018;119:97–103. https://doi.org/10.1016/j.urology.2017.09.011.CrossRefPubMed

69.

Spivak L, Shultz T, Appel B, Verze P, Yagudaev D, Vinarov A. Low-intensity extracorporeal shockwave therapy for erectile dysfunction in diabetic patients. Sex Med Rev. 2019. https://doi.org/10.1016/j.sxmr.2019.06.007.

70.

Matz EL, Terlecki R, Zhang Y, Jackson J, Atala A. Stem Cell Therapy for erectile dysfunction. Sex Med Rev. 2019;7(2):321–8. https://doi.org/10.1016/j.sxmr.2017.12.008.CrossRefPubMed

71.

Scott S, Roberts M, Chung E. Platelet-rich plasma and treatment of erectile dysfunction: critical review of literature and global trends in platelet-rich plasma clinics. Sex Med Rev. 2019;7(2):306–12. https://doi.org/10.1016/j.sxmr.2018.12.006.CrossRefPubMed

72.

SMSNA Position statement on restorative therapies for ED. http://www.smsna.org/V1/about/position-statements. Accessed December 24, 2018.

73.

Singh R, Artaza JN, Taylor WE, Gonzalez-Cadavid NF, Bhasin S. Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology. 2003;144(11):5081–8. https://doi.org/10.1210/en.2003-0741.CrossRefPubMed

74.

Bhasin S, Storer TW, Berman N, et al. Testosterone replacement increases fat-free mass and muscle size in hypogonadal men. J Clin Endocrinol Metab. 1997;82(2):407–13. https://doi.org/10.1210/jcem.82.2.3733.CrossRefPubMed

75.

Wang C, Swerdloff RS, Iranmanesh A, et al. Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. J Clin Endocrinol Metab. 2000;85(8):2839–53. https://doi.org/10.1210/jcem.85.8.6747.CrossRefPubMed

76.

Isidori AM, Giannetta E, Greco EA, Gianfrilli D, Bonifacio V, Isidori A, et al. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol. 2005;63(3):280–93. https://doi.org/10.1111/j.1365-2265.2005.02339.x.CrossRef

77.

• Dhindsa S, Ghanim H, Batra M, et al. Insulin resistance and inflammation in hypogonadotropic hypogonadism and their reduction after testosterone replacement in men with type 2 diabetes. Diabetes Care. 2016;39(1):82–91. https://doi.org/10.2337/dc15-1518After 24 weeks of testosterone therapy, hypogonadal diabetic men had improved insulin sensitivity and body composition. CrossRefPubMed

78.

Osuna JA, Gómez-Pérez R, Arata-Bellabarba G, Villaroel V. Relationship between BMI, total testosterone, sex hormone-binding-globulin, leptin, insulin and insulin resistance in obese men. Arch Androl. 2006;52(5):355–61. https://doi.org/10.1080/01485010600692017.CrossRefPubMed

79.

Traish AM, Saad F, Guay A. The dark side of testosterone deficiency: II. type 2 diabetes and insulin resistance. J Androl. 2008;30(1):23–32. https://doi.org/10.2164/jandrol.108.005751.CrossRefPubMed

80.

Selvin E, Feinleib M, Zhang L, et al. Androgens and diabetes in men: results from the Third National Health and Nutrition Examination Survey (NHANES III). Diabetes Care. 2007;30(2):234–8. https://doi.org/10.2337/dc06-1579.CrossRefPubMed

81.

Sarnak MJ, Tighiouart H, Manjunath G, et al. Anemia as a risk factor for cardiovascular disease in the atherosclerosis risk in communities (aric) study. J Am Coll Cardiol. 2002;40(1):27–33. https://doi.org/10.1016/S0735-1097(02)01938-1.CrossRefPubMed

82.

Bhatia V, Chaudhuri A, Tomar R, Dhindsa S, Ghanim H, Dandona P. Low testosterone and high C-reactive protein concentrations predict low hematocrit in type 2 diabetes. Diabetes Care. 2006;29(10):2289–94. https://doi.org/10.2337/dc06-0637.CrossRefPubMed

83.

Grossmann M, Panagiotopolous S, Sharpe K, MacIsaac R, Clarke S, Zajac JD, et al. Low testosterone and anaemia in men with type 2 diabetes. Clin Endocrinol. 2009;70(4):547–53. https://doi.org/10.1111/j.1365-2265.2008.03357.x.CrossRef

84.

Roy CN, Snyder PJ, Stephens-Shields AJ, Artz AS, Bhasin S, Cohen HJ, et al. Association of testosterone levels with anemia in older men: a controlled clinical trial. JAMA Intern Med. 2017;177(4):480–90. https://doi.org/10.1001/jamainternmed.2016.9540.CrossRefPubMedPubMedCentral

85.

Bachman E, Travison TG, Basaria S, Davda MN, Guo W, Li M, et al. Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point. J Gerontol A Biol Sci Med Sci. 2014;69(6):725–35. https://doi.org/10.1093/gerona/glt154.CrossRefPubMed

86.

Pastuszak AW, Kohn TP, Estis J, Lipshultz LI. Low plasma testosterone is associated with elevated cardiovascular disease biomarkers. J Sex Med. 2017;14(9):1095–103. https://doi.org/10.1016/j.jsxm.2017.06.015.CrossRefPubMedPubMedCentral

87.

• Farias JM, Tinetti M, Khoury M, Umpierrez GE, et al. J Clin Endocrinol Metab. 2014;99(12):4698–703. https://doi.org/10.1210/jc.2014-2585In middle-aged diabetic men, low testosterone associated with increased levels of atherosclerotic disease parameters. CrossRefPubMedPubMedCentral

88.

Daka B, Langer RD, Larsson CA, Rosén T, Jansson PA, Råstam L, et al. Low concentrations of serum testosterone predict acute myocardial infarction in men with type 2 diabetes mellitus. BMC Endocr Disord. 2015;15:35–7. https://doi.org/10.1186/s12902-015-0034-1.CrossRefPubMedPubMedCentral

89.

Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab. 2008;93(1):68–75. https://doi.org/10.1210/jc.2007-1792.CrossRefPubMed

90.

Muraleedharan V, Marsh H, Kapoor D, Channer KS, Jones TH. Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Eur J Endocrinol. 2013;169(6):725–33. https://doi.org/10.1530/EJE-13-0321.CrossRefPubMed

91.

Tomar R, Dhindsa S, Chaudhuri A, Mohanty P, Garg R, Dandona P. Contrasting testosterone concentrations in type 1 and type 2 diabetes. Diabetes Care. 2006;29(5):1120–2. https://doi.org/10.2337/dc06-0197.CrossRefPubMed

92.

Corona G, Rastrelli G, Monami M, Saad F, Luconi M, Lucchese M, et al. Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis. Eur J Endocrinol. 2013;168(6):829–43. https://doi.org/10.1530/EJE-12-0955.CrossRefPubMed

93.

Bekaert M, Van Nieuwenhove Y, Calders P, et al. Determinants of testosterone levels in human male obesity. Endocrine. 2015;50(1):202–11. https://doi.org/10.1007/s12020-015-0563-4.CrossRefPubMedPubMedCentral

94.

Mogri M, Dhindsa S, Quattrin T, Ghanim H, Dandona P. Testosterone concentrations in young pubertal and post-pubertal obese males. Clin Endocrinol. 2013;78(4):593–9. https://doi.org/10.1111/cen.12018.CrossRef

95.

Dhindsa S, Furlanetto R, Vora M, Ghanim H, Chaudhuri A, Dandona P. Low estradiol concentrations in men with subnormal testosterone concentrations and type 2 diabetes. Diabetes Care. 2011;34(8):1854–9. https://doi.org/10.2337/dc11-0208.CrossRefPubMedPubMedCentral

96.

Tajar A, Forti G, O’Neill TW, et al. Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. J Clin Endocrinol Metab. 2010;95(4):1810–8. https://doi.org/10.1210/jc.2009-1796.CrossRefPubMed

97.

Esser N, Legrand-Poels S, Piette J, Scheen AJ, Paquot N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract. 2014;105(2):141–50. https://doi.org/10.1016/j.diabres.2014.04.006.CrossRefPubMed

98.

Bobjer J, Katrinaki M, Tsatsanis C, Lundberg Giwercman Y, Giwercman A. Negative association between testosterone concentration and inflammatory markers in young men: a nested cross-sectional study. PLoS One. 2013;8(4):e61466. https://doi.org/10.1371/journal.pone.0061466.CrossRefPubMedPubMedCentral

99.

Tsatsanis C, Dermitzaki E, Avgoustinaki P, Malliaraki N, Mytaras V, Margioris AN. The impact of adipose tissue-derived factors on the hypothalamic-pituitary-gonadal (HPG) axis. Hormones. 2015;14(4):549–62. https://doi.org/10.14310/horm.2002.1649.CrossRefPubMed

100.

Landry D, Cloutier F, Martin LJ. Implications of leptin in neuroendocrine regulation of male reproduction. Reprod Biol. 2013;13(1):1–14. https://doi.org/10.1016/j.repbio.2012.12.001.CrossRefPubMed

101.

Sáinz N, Barrenetxe J, Moreno-Aliaga MJ, Martínez JA. Leptin resistance and diet-induced obesity: central and peripheral actions of leptin. Metabolism. 2015;64(1):35–46. https://doi.org/10.1016/j.metabol.2014.10.015.CrossRefPubMed

102.

Brüning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, et al. Role of brain insulin receptor in control of body weight and reproduction. Science. 2000;289(5487):2122–5.CrossRef

103.

Salvi R, Castillo E, Voirol M-J, et al. Gonadotropin-releasing hormone-expressing neurons immortalized conditionally are activated by insulin: implication of the mitogen-activated protein kinase pathway. Endocrinology. 2006;147(2):816–26. https://doi.org/10.1210/en.2005-0728.CrossRefPubMed

104.

Kullmann S, Heni M, Hallschmid M, Fritsche A, Preissl H, Häring H-U. Brain insulin resistance at the crossroads of metabolic and cognitive disorders in humans. Physiol Rev. 2016;96(4):1169–209. https://doi.org/10.1152/physrev.00032.2015.CrossRefPubMed

105.

•• Ghanim H, Dhindsa S, Abuaysheh S, et al. Diminished androgen and estrogen receptors and aromatase levels in hypogonadal diabetic men: reversal with testosterone. Eur J Endocrinol. 2018;178(3):277–83. https://doi.org/10.1530/EJE-17-0673Randomized double-blind placebo-controlled trial demonstrating that hypogonadal diabetics have decreased aromatase, androgen receptor, and estrogen receptor expression rather than the hypothesized compensatory increased expression. This was reversed with testosterone therapy. CrossRefPubMed

106.

Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423–32. https://doi.org/10.1016/j.juro.2018.03.115.CrossRefPubMed

107.

Dean JD, McMahon CG, Guay AT, Morgentaler A, Althof SE, Becher EF, et al. The International Society for Sexual Medicine’s process of care for the assessment and management of testosterone deficiency in adult men. J Sex Med. 2015;12(8):1660–86. https://doi.org/10.1111/jsm.12952.CrossRefPubMed

108.

• Hackett G, Heald AH, Sinclair A, Jones PW, Strange RC, Ramachandran S. Serum testosterone, testosterone replacement therapy and all-cause mortality in men with type 2 diabetes: retrospective consideration of the impact of PDE5 inhibitors and statins. Int J Clin Pract. 2016;70(3):244–53. https://doi.org/10.1111/ijcp.12779Retrospective analysis demonstrating that testosterone therapy was independently associated with decreased mortality in diabetic men. In addition, PDE5i usage was independently associated with reduced mortality regardless of testosterone therapy usage. CrossRefPubMed

109.

•• Hackett G, Cole N, Mulay A, Strange RC, Ramachandran S. Long-term testosterone therapy in type 2 diabetes is associated with reduced mortality without improvement in conventional cardiovascular risk factors. BJU Int. 2019;123(3):519–29. https://doi.org/10.1111/bju.14536Analysis of men in the BLAST trial demonstrating that long-term testosterone therapy in men with DM2 associated with reduced mortality unrelated to improvement in traditional CVD risk factors. CrossRefPubMed

110.

Contraceptive efficacy of testosterone-induced azoospermia in normal men. World Health Organization Task Force on methods for the regulation of male fertility. Lancet Lond Engl. 1990;336(8721):955–9.

111.

Gui Y-L, He C-H, Amory JK, et al. Male hormonal contraception: suppression of spermatogenesis by injectable testosterone undecanoate alone or with levonorgestrel implants in chinese men. J Androl. 2004;25(5):720–7.CrossRef

112.

McBride JA, Coward RM. Recovery of spermatogenesis following testosterone replacement therapy or anabolic-androgenic steroid use. Asian J Androl. 2016;18(3):373–80. https://doi.org/10.4103/1008-682X.173938.CrossRefPubMedPubMedCentral

113.

Wenker EP, Dupree JM, Langille GM, et al. The use of HCG-based combination therapy for recovery of spermatogenesis after testosterone use. J Sex Med. 2015;12(6):1334–7. https://doi.org/10.1111/jsm.12890.CrossRefPubMed

114.

Wheeler KM, Smith RP, Kumar RA, Setia S, Costabile RA, Kavoussi PK. A comparison of secondary polycythemia in hypogonadal men treated with clomiphene citrate versus testosterone replacement: a multi-institutional study. J Urol. 2017;197(4):1127–31. https://doi.org/10.1016/j.juro.2016.10.068.CrossRefPubMed

115.

Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, et al. Effects of testosterone treatment in older men. N Engl J Med. 2016;374(7):611–24. https://doi.org/10.1056/NEJMoa1506119.CrossRefPubMedPubMedCentral

116.

Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, et al. Lessons from the testosterone trials. Endocr Rev. 2018;39(3):369–86. https://doi.org/10.1210/er.2017-00234.CrossRefPubMedPubMedCentral

117.

Morgentaler A, Miner MM, Caliber M, Guay AT, Khera M, Traish AM. Testosterone therapy and cardiovascular risk: advances and controversies. Mayo Clin Proc. 2015;90(2):224–51. https://doi.org/10.1016/j.mayocp.2014.10.011.CrossRefPubMed

118.

Sharma R, Oni OA, Chen G, Sharma M, Dawn B, Sharma R, et al. Association between testosterone replacement therapy and the incidence of DVT and pulmonary embolism: a retrospective cohort study of the Veterans Administration Database. Chest. 2016;150(3):563–71. https://doi.org/10.1016/j.chest.2016.05.007.CrossRefPubMed

119.

Kavoussi PK, Machen GL, Wenzel JL, Ellis AM, Kavoussi M, Kavoussi KM, et al. Medical treatments for hypogonadism do not significantly increase the risk of deep vein thrombosis over general population risk. Urology. 2019;124:127–30. https://doi.org/10.1016/j.urology.2018.11.009.CrossRefPubMed

120.

Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, et al. Testosterone therapy in men with hypogonadism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715–44. https://doi.org/10.1210/jc.2018-00229.CrossRefPubMed

121.

Tatem AJ, Beilan J, Kovac JR, Lipshultz LI. Management of anabolic steroid-induced infertility: novel strategies for fertility maintenance and recovery. World J Mens Health. 2019. https://doi.org/10.5534/wjmh.190002.

122.

Pelusi C, Giagulli VA, Baccini M, Fanelli F, Mezzullo M, Fazzini A, et al. Clomiphene citrate effect in obese men with low serum testosterone treated with metformin due to dysmetabolic disorders: a randomized, double-blind, placebo-controlled study. PLoS One. 2017;12(9):e0183369. https://doi.org/10.1371/journal.pone.0183369.CrossRefPubMedPubMedCentral

123.

Scovell JM, Khera M. Testosterone replacement therapy versus clomiphene citrate in the young hypogonadal male. Eur Urol Focus. 2018;4(3):321–3. https://doi.org/10.1016/j.euf.2018.07.033.CrossRefPubMed

124.

Dadhich P, Ramasamy R, Scovell J, Wilken N, Lipshultz L. Testosterone versus clomiphene citrate in managing symptoms of hypogonadism in men. Indian J Urol IJU J Urol Soc India. 2017;33(3):236–40. https://doi.org/10.4103/iju.IJU_372_16.CrossRef

125.

Habous M, Giona S, Tealab A, Aziz M, Williamson B, Nassar M, et al. Clomiphene citrate and human chorionic gonadotropin are both effective in restoring testosterone in hypogonadism: a short-course randomized study. BJU Int. 2018;122(5):889–97. https://doi.org/10.1111/bju.14401.CrossRefPubMed

126.

Raman JD, Schlegel PN. Aromatase inhibitors for male infertility. J Urol. 2002;167(2 Pt 1):624–9.CrossRef

Titel: The Complex Relationship Between Erectile Dysfunction and Hypogonadism in Diabetes Mellitus
verfasst von: Levi C. Holland, B.S.
Jonathan A. Beilan, M.D.
Alexander J. Tatem, M.D.
Larry I. Lipshultz, M.D.
Publikationsdatum: 06.11.2019
Verlag: Springer US
Erschienen in: Current Sexual Health Reports / Ausgabe 4/2019
Print ISSN: 1548-3584
Elektronische ISSN: 1548-3592
DOI: https://doi.org/10.1007/s11930-019-00216-9

The Significance of Sexual Debut in Women’s Lives

Female Sexual Dysfunction and Disorders (T Lorenz and R Nappi, Section Editors)

Premature Ejaculation: 2020 Update

Urology, Gynecology, and Endocrinology (J Simon and M Luria, Section Editors)

What Constitutes Mutilation? A Concern With Anti-Female Genital Mutilation Laws in Australia and the Question of Natural Function

Sociocultural Issues and Epidemiology (J Abdulcadir and C Johnson-Agbakwu, Section Editors)

Female Sexual Dysfunction as a Warning Sign of Chronic Disease Development

Female Sexual Dysfunction and Disorders (T Lorenz & R Nappi, Section Editors)

A Review of Genome Wide Association Studies for Erectile Dysfunction

Female Sexual Dysfunction and Disorders (A Pastuszak and N Thirumavalavan, Section Editors)

Recent Advances and Future Opportunities to Diagnose Male Infertility

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The Complex Relationship Between Erectile Dysfunction and Hypogonadism in Diabetes Mellitus

Abstract

Purpose of Review

Recent Findings

Summary

Weitere Artikel der Ausgabe 4/2019

The Significance of Sexual Debut in Women’s Lives

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