Skip to main content

Advertisement

Log in

Interactions between erectile dysfunction, cardiovascular disease and cardiovascular drugs

  • Review Article
  • Published:

From Nature Reviews Cardiology

View current issue Sign up to alerts

Abstract

Sexual health has a fundamental role in overall health and well-being, and a healthy and dynamic sex life can make an important contribution to a good quality of life. Sexual dysfunction, and especially erectile dysfunction (ED) in men, is highly prevalent in patients with cardiovascular disease (CVD). CVD and ED have shared risk factors and pathophysiological links, such as endothelial dysfunction, inflammation and low plasma testosterone levels. ED has been shown to be an independent and early harbinger of future CVD events, providing an important window to initiate preventive measures. Therefore, screening and diagnosing ED is essential for the primary and secondary prevention of CVD because the assessment of ED offers an easy and low-cost prognostic tool that is an alternative to other investigational cardiovascular biomarkers. Moreover, ED is a major contributing factor to the discontinuation of, or poor adherence to, cardiovascular therapy. Cardiovascular drugs have divergent effects on erectile function, with diuretics and β-blockers having the worst profiles, and renin–angiotensin–aldosterone system inhibitors and nebivolol having the best profiles. Pharmacological treatment of ED has an equivocal effect on the risk of CVD, suggesting a complex interaction between ED and drugs for CVD. In this Review, we discuss how sexual function could be incorporated into the patient history taken by physicians treating individuals with CVD, not merely as part of the diagnostic work-up but as a means to pursue tangible and essential benefits in quality of life and cardiovascular outcomes.

Key points

  • Erectile dysfunction (ED) is common, especially with advancing age, and shares risk factors and pathophysiological mechanisms with cardiovascular disease (CVD).

  • ED is highly prevalent in men with CVD, often precedes a CVD event by 2–5 years and is a marker of general vascular disease.

  • ED predicts cardiovascular events and all-cause mortality especially in men with an intermediate CVD risk score, who need further evaluation for CVD.

  • Some CVD medications, such as β-blockers and diuretics, have a deleterious effect on erectile function, and physicians should be aware of these adverse effects.

  • Phosphodiesterase type 5 inhibitors are not only safe for the cardiovascular system but also seem to have beneficial effects on the vasculature that could explain promising results in prognostic studies.

  • Testosterone replacement therapy has shown conflicting results in terms of CVD risk and should be administered with close monitoring for possible adverse effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1: The shared pathways leading to ED and CVD.
Fig. 2: An algorithm for managing ED associated with cardiovascular drug therapy.
Fig. 3: Evaluation of ED and risk assessment for sexual activity in patients with CVD.

Similar content being viewed by others

References

  1. Shah, J. Erectile dysfunction through the ages. BJU Int. 90, 433–441 (2002).

    CAS  PubMed  Google Scholar 

  2. Goldstein, I., Burnett, A. L., Rosen, R. C., Park, P. W. & Stecher, V. J. The serendipitous story of sildenafil: an unexpected oral therapy for erectile dysfunction. Sex. Med. Rev. 7, 115–128 (2019).

    PubMed  Google Scholar 

  3. Feldman, H. A., Goldstein, I., Hatzichristou, D. G., Krane, R. J. & McKinlay, J. B. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J. Urol. 151, 54–61 (1994).

    CAS  PubMed  Google Scholar 

  4. Vlachopoulos, C., Ioakeimidis, N., Terentes-Printzios, D. & Stefanadis, C. The triad: erectile dysfunction–endothelial dysfunction–cardiovascular disease. Curr. Pharm. Des. 14, 3700–3714 (2008).

    CAS  PubMed  Google Scholar 

  5. Miner, M. M. Erectile dysfunction: a harbinger or consequence: does its detection lead to a window of curability? J. Androl. 32, 125–134 (2011).

    PubMed  Google Scholar 

  6. Arnett, D. K. et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J. Am. Coll. Cardiol. 74, e177–e232 (2019).

    PubMed  PubMed Central  Google Scholar 

  7. Vlachopoulos, C., Jackson, G., Stefanadis, C. & Montorsi, P. Erectile dysfunction in the cardiovascular patient. Eur. Heart J. 34, 2034–2046 (2013).

    PubMed  Google Scholar 

  8. Piepoli, M. F. et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts). Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur. Heart J. 37, 2315–2381 (2016).

    PubMed  PubMed Central  Google Scholar 

  9. Viigimaa, M. et al. Update of the position paper on arterial hypertension and erectile dysfunction. J. Hypertens. 38, 1220–1234 (2020).

    CAS  PubMed  Google Scholar 

  10. Vlachopoulos, C., Terentes-Printzios, D., Ioakeimidis, N., Rokkas, K. & Stefanadis, C. PDE5 inhibitors in non-urological conditions. Curr. Pharm. Des. 15, 3521–3539 (2009).

    CAS  PubMed  Google Scholar 

  11. Shamloul, R. & Ghanem, H. Erectile dysfunction. Lancet 381, 153–165 (2013).

    CAS  PubMed  Google Scholar 

  12. Yafi, F. A. et al. Erectile dysfunction. Nat. Rev. Dis. Prim. 2, 16003 (2016).

    PubMed  Google Scholar 

  13. Montorsi, P., Montorsi, F. & Schulman, C. C. Is erectile dysfunction the “tip of the iceberg” of a systemic vascular disorder? Eur. Urol. 44, 352–354 (2003).

    PubMed  Google Scholar 

  14. Gutterman, D. D. et al. The human microcirculation: regulation of flow and beyond. Circ. Res. 118, 157–172 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Meldrum, D. R. et al. The link between erectile and cardiovascular health: the canary in the coal mine. Am. J. Cardiol. 108, 599–606 (2011).

    PubMed  Google Scholar 

  16. Vlachopoulos, C. et al. Prediction of cardiovascular events with aortic stiffness in patients with erectile dysfunction. Hypertension 64, 672–678 (2014).

    CAS  PubMed  Google Scholar 

  17. Corona, G. et al. Pulse pressure independently predicts major cardiovascular events in younger but not in older subjects with erectile dysfunction. J. Sex. Med. 8, 247–254 (2011).

    PubMed  Google Scholar 

  18. Rastrelli, G., Corona, G., Mannucci, E. & Maggi, M. Vascular and chronological age in men with erectile dysfunction: a longitudinal study. J. Sex. Med. 13, 200–208 (2016).

    PubMed  Google Scholar 

  19. Vlachopoulos, C. et al. Unfavourable endothelial and inflammatory state in erectile dysfunction patients with or without coronary artery disease. Eur. Heart J. 27, 2640–2648 (2006).

    CAS  PubMed  Google Scholar 

  20. Climie, R. E., Bruno, R. M., Hametner, B., Mayer, C. C. & Terentes-Printzios, D. Vascular age is not only atherosclerosis, it is also arteriosclerosis. J. Am. Coll. Cardiol. 76, 229–230 (2020).

    PubMed  Google Scholar 

  21. Vita, J. A. et al. Brachial artery vasodilator function and systemic inflammation in the Framingham Offspring Study. Circulation 110, 3604–3609 (2004).

    CAS  PubMed  Google Scholar 

  22. Vlachopoulos, C. et al. Acute systemic inflammation increases arterial stiffness and decreases wave reflections in healthy individuals. Circulation 112, 2193–2200 (2005).

    PubMed  Google Scholar 

  23. Vlachopoulos, C., Rokkas, K., Ioakeimidis, N. & Stefanadis, C. Inflammation, metabolic syndrome, erectile dysfunction, and coronary artery disease: common links. Eur. Urol. 52, 1590–1600 (2007).

    CAS  PubMed  Google Scholar 

  24. Reis, F. M. & Reis, A. M. Angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7) and Mas receptor in gonadal and reproductive functions. Clin. Sci. 134, 2929–2941 (2020).

    CAS  Google Scholar 

  25. de Oliveira, A. A. & Nunes, K. P. Hypertension and erectile dysfunction: breaking down the challenges. Am. J. Hypertens. 34, 134–142 (2021).

    PubMed  Google Scholar 

  26. Kloner, R. A., Carson, C. 3rd, Dobs, A., Kopecky, S. & Mohler, E. R. 3rd Testosterone and cardiovascular disease. J. Am. Coll. Cardiol. 67, 545–557 (2016).

    CAS  PubMed  Google Scholar 

  27. Vlachopoulos, C. et al. Plasma total testosterone and incident cardiovascular events in hypertensive patients. Am. J. Hypertens. 26, 373–381 (2013).

    CAS  PubMed  Google Scholar 

  28. Corona, G. et al. Endogenous testosterone levels and cardiovascular risk: meta-analysis of observational studies. J. Sex. Med. 15, 1260–1271 (2018).

    PubMed  Google Scholar 

  29. Hannan, J. L. et al. Impact of hypertension, aging, and antihypertensive treatment on the morphology of the pudendal artery. J. Sex. Med. 8, 1027–1038 (2011).

    CAS  PubMed  Google Scholar 

  30. Rogers, J. H. et al. Zotarolimus-eluting peripheral stents for the treatment of erectile dysfunction in subjects with suboptimal response to phosphodiesterase-5 inhibitors. J. Am. Coll. Cardiol. 60, 2618–2627 (2012).

    CAS  PubMed  Google Scholar 

  31. Sangiorgi, G. et al. Endovascular therapy for erectile dysfunction: a state of the art review. Minerva Cardioangiol. https://doi.org/10.23736/S0026-4725.20.05136-1 (2020).

    Article  PubMed  Google Scholar 

  32. Corona, G. et al. Erectile dysfunction and cardiovascular risk: a review of current findings. Expert. Rev. Cardiovasc. Ther. 18, 155–164 (2020).

    CAS  PubMed  Google Scholar 

  33. Saigal, C. S. et al. Predictors and prevalence of erectile dysfunction in a racially diverse population. Arch. Intern. Med. 166, 207–212 (2006).

    PubMed  Google Scholar 

  34. Polonsky, T. S. et al. The association between erectile dysfunction and peripheral arterial disease as determined by screening ankle-brachial index testing. Atherosclerosis 207, 440–444 (2009).

    CAS  PubMed  Google Scholar 

  35. Böhm, M. et al. Sexual function, satisfaction, and association of erectile dysfunction with cardiovascular disease and risk factors in cardiovascular high-risk patients: substudy of the ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNT Study in ACE-INtolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND). Am. Heart J. 154, 94–101 (2007).

    PubMed  Google Scholar 

  36. Montorsi, F. et al. Erectile dysfunction prevalence, time of onset and association with risk factors in 300 consecutive patients with acute chest pain and angiographically documented coronary artery disease. Eur. Urol. 44, 360–364 (2003).

    PubMed  Google Scholar 

  37. Montorsi, P. et al. Association between erectile dysfunction and coronary artery disease. Role of coronary clinical presentation and extent of coronary vessels involvement: the COBRA trial. Eur. Heart J. 27, 2632–2639 (2006).

    PubMed  Google Scholar 

  38. Terentes-Printzios, D., Vlachopoulos, C., Ioakeimidis, N., Aznaouridis, K. & Stefanadis, C. Erectile dysfunction severity and prediction of cardiovascular events and all-cause mortality: a systematic review and meta-analysis of cohort studies. Eur. Heart J. 34, 957–958 (2013).

    Google Scholar 

  39. Zhao, B. et al. Erectile dysfunction predicts cardiovascular events as an independent risk factor: a systematic review and meta-analysis. J. Sex. Med. 16, 1005–1017 (2019).

    PubMed  Google Scholar 

  40. Montorsi, P. et al. Common grounds for erectile dysfunction and coronary artery disease. Curr. Opin. Urol. 14, 361–365 (2004).

    PubMed  Google Scholar 

  41. Vlachopoulos, C. et al. Prevalence of asymptomatic coronary artery disease in men with vasculogenic erectile dysfunction: a prospective angiographic study. Eur. Urol. 48, 996–1002 (2005).

    PubMed  Google Scholar 

  42. Enbergs, A. et al. Prevalence of coronary artery disease in a general population without suspicion of coronary artery disease: angiographic analysis of subjects aged 40 to 70 years referred for catheter ablation therapy. Eur. Heart J. 21, 45–52 (2000).

    CAS  PubMed  Google Scholar 

  43. Terentes-Printzios, D. et al. The prevalence and predicitive role of erectile dysfunction in acute coronary syndrome patients [abstract]. Eur. Heart J. 37, 968 (2016).

    Google Scholar 

  44. Jackson, G. Erectile dysfunction and asymptomatic coronary artery disease: frequently detected by computed tomography coronary angiography but not by exercise electrocardiography. Int. J. Clin. Pract. 67, 1159–1162 (2013).

    CAS  PubMed  Google Scholar 

  45. Schonhofen, J. et al. Incidental findings during computed tomographic angiography diagnostic work-up in patients with arteriogenic erectile dysfunction. Swiss Med. Wkly 149, w20154 (2019).

    PubMed  Google Scholar 

  46. Feldman, D. I. et al. Subclinical vascular disease and subsequent erectile dysfunction: the Multiethnic Study of Atherosclerosis (MESA). Clin. Cardiol. 39, 291–298 (2016).

    PubMed  PubMed Central  Google Scholar 

  47. Jaarsma, T. Sexual function of patients with heart failure: facts and numbers. ESC. Heart Fail. 4, 3–7 (2017).

    PubMed  Google Scholar 

  48. Alberti, L. et al. Erectile dysfunction in heart failure patients: a critical reappraisal. Andrology 1, 177–191 (2013).

    CAS  PubMed  Google Scholar 

  49. Apostolo, A. et al. Erectile dysfunction in heart failure: correlation with severity, exercise performance, comorbidities, and heart failure treatment. J. Sex. Med. 6, 2795–2805 (2009).

    CAS  PubMed  Google Scholar 

  50. Baumhäkel, M. & Böhm, M. Erectile dysfunction correlates with left ventricular function and precedes cardiovascular events in cardiovascular high-risk patients. Int. J. Clin. Pract. 61, 361–366 (2007).

    PubMed  Google Scholar 

  51. Vural, A. et al. Effect of cardiac resynchronization therapy on libido and erectile dysfunction. Clin. Cardiol. 34, 437–441 (2011).

    PubMed  PubMed Central  Google Scholar 

  52. El-Sakka, A. I., Morsy, A. M. & Fagih, B. I. Severity of erectile dysfunction could predict left ventricular diastolic dysfunction in patients without overt cardiac complaint. J. Sex. Med. 8, 2590–2597 (2011).

    PubMed  Google Scholar 

  53. Koutsampasopoulos, K. et al. Right ventricular function and sexual function: exploring shadows in male and female patients with heart failure. J. Sex. Med. 16, 1199–1211 (2019).

    PubMed  Google Scholar 

  54. Gandaglia, G. et al. A systematic review of the association between erectile dysfunction and cardiovascular disease. Eur. Urol. 65, 968–978 (2014).

    PubMed  Google Scholar 

  55. Thompson, I. M. et al. Erectile dysfunction and subsequent cardiovascular disease. JAMA 294, 2996–3002 (2005).

    CAS  PubMed  Google Scholar 

  56. Banks, E. et al. Erectile dysfunction severity as a risk marker for cardiovascular disease hospitalisation and all-cause mortality: a prospective cohort study. PLoS Med. 10, e1001372 (2013).

    PubMed  PubMed Central  Google Scholar 

  57. Ioakeimidis, N. et al. Relationship of asymmetric dimethylarginine with penile Doppler ultrasound parameters in men with vasculogenic erectile dysfunction. Eur. Urol. 59, 948–955 (2011).

    CAS  PubMed  Google Scholar 

  58. Ioakeimidis, N. et al. Dynamic penile peak systolic velocity predicts major adverse cardiovascular events in hypertensive patients with erectile dysfunction. J. Hypertens. 34, 860–868 (2016).

    CAS  PubMed  Google Scholar 

  59. Corona, G. et al. Male sexuality and cardiovascular risk. A cohort study in patients with erectile dysfunction. J. Sex. Med. 7, 1918–1927 (2010).

    PubMed  Google Scholar 

  60. Gazzaruso, C. et al. 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. 51, 2040–2044 (2008).

    PubMed  Google Scholar 

  61. Ma, R. C. et al. Erectile dysfunction predicts coronary heart disease in type 2 diabetes. J. Am. Coll. Cardiol. 51, 2045–2050 (2008).

    PubMed  Google Scholar 

  62. Batty, G. D. et al. Erectile dysfunction and later cardiovascular disease in men with type 2 diabetes: prospective cohort study based on the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation) trial. J. Am. Coll. Cardiol. 56, 1908–1913 (2010).

    PubMed  PubMed Central  Google Scholar 

  63. Turek, S. J., Hastings, S. M., Sun, J. K., King, G. L. & Keenan, H. A. Sexual dysfunction as a marker of cardiovascular disease in males with 50 or more years of type 1 diabetes. Diabetes Care 36, 3222–3226 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Yamada, T., Hara, K., Umematsu, H., Suzuki, R. & Kadowaki, T. Erectile dysfunction and cardiovascular events in diabetic men: a meta-analysis of observational studies. PLoS ONE 7, e43673 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Böhm, M. et al. Erectile dysfunction predicts cardiovascular events in high-risk patients receiving telmisartan, ramipril, or both: The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (ONTARGET/TRANSCEND) Trials. Circulation 121, 1439–1446 (2010).

    PubMed  Google Scholar 

  66. Hebert, K. et al. Peripheral vascular disease and erectile dysfunction as predictors of mortality in heart failure patients. J. Sex. Med. 6, 1999–2007 (2009).

    PubMed  Google Scholar 

  67. Ponholzer, A., Gutjahr, G., Temml, C. & Madersbacher, S. Is erectile dysfunction a predictor of cardiovascular events or stroke? A prospective study using a validated questionnaire. Int. J. Impot. Res. 22, 25–29 (2010).

    CAS  PubMed  Google Scholar 

  68. Hotaling, J. M. et al. Erectile dysfunction is not independently associated with cardiovascular death: data from the vitamins and lifestyle (VITAL) study. J. Sex. Med. 9, 2104–2110 (2012).

    PubMed  Google Scholar 

  69. Rosen, R. C., Cappelleri, J. C., Smith, M. D., Lipsky, J. & Pena, B. M. Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int. J. Impot. Res. 11, 319–326 (1999).

    CAS  PubMed  Google Scholar 

  70. Vlachopoulos, C. V., Terentes-Printzios, D. G., Ioakeimidis, N. K., Aznaouridis, K. A. & Stefanadis, C. I. Prediction of cardiovascular events and all-cause mortality with erectile dysfunction: a systematic review and meta-analysis of cohort studies. Circ. Cardiovasc. Qual. Outcomes 6, 99–109 (2013).

    PubMed  Google Scholar 

  71. Terentes-Printzios, D. et al. Cardiovascular risk factors accelerate progression of vascular aging in the general population: results from the CRAVE study (Cardiovascular Risk Factors Affecting Vascular Age). Hypertension 70, 1057–1064 (2017).

    CAS  PubMed  Google Scholar 

  72. Araujo, A. B. et al. Does erectile dysfunction contribute to cardiovascular disease risk prediction beyond the Framingham risk score? J. Am. Coll. Cardiol. 55, 350–356 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Dong, J. Y., Zhang, Y. H. & Qin, L. Q. Erectile dysfunction and risk of cardiovascular disease: meta-analysis of prospective cohort studies. J. Am. Coll. Cardiol. 58, 1378–1385 (2011).

    PubMed  Google Scholar 

  74. Osondu, C. U. et al. The relationship of erectile dysfunction and subclinical cardiovascular disease: a systematic review and meta-analysis. Vasc. Med. 23, 9–20 (2018).

    PubMed  Google Scholar 

  75. Guo, W. et al. Erectile dysfunction and risk of clinical cardiovascular events: a meta-analysis of seven cohort studies. J. Sex. Med. 7, 2805–2816 (2010).

    PubMed  Google Scholar 

  76. Fan, Y., Hu, B., Man, C. & Cui, F. Erectile dysfunction and risk of cardiovascular and all-cause mortality in the general population: a meta-analysis of cohort studies. World J. Urol. 36, 1681–1689 (2018).

    PubMed  Google Scholar 

  77. Zhao, B. & Zhang, W. Does erectile dysfunction independently predict cardiovascular events? It’s time to act on the evidence. Eur. J. Prev. Cardiol. 25, 1307–1311 (2018).

    PubMed  Google Scholar 

  78. Dahabreh, I. J. & Paulus, J. K. Association of episodic physical and sexual activity with triggering of acute cardiac events: systematic review and meta-analysis. JAMA 305, 1225–1233 (2011).

    PubMed  PubMed Central  Google Scholar 

  79. Levine, G. N. et al. Sexual activity and cardiovascular disease: a scientific statement from the American Heart Association. Circulation 125, 1058–1072 (2012).

    PubMed  Google Scholar 

  80. Lindau, S. T. et al. Sexual activity and counseling in the first month after acute myocardial infarction among younger adults in the United States and Spain: a prospective, observational study. Circulation 130, 2302–2309 (2014).

    PubMed  PubMed Central  Google Scholar 

  81. Steinke, E. E., Mosack, V. & Hill, T. J. Change in sexual activity after a cardiac event: the role of medications, comorbidity, and psychosocial factors. Appl. Nurs. Res. 28, 244–250 (2015).

    PubMed  Google Scholar 

  82. Brandis Kepler, S., Hasin, T., Benyamini, Y., Goldbourt, U. & Gerber, Y. Frequency of sexual activity and long-term survival after acute myocardial infarction. Am. J. Med. 133, 100–107 (2020).

    PubMed  Google Scholar 

  83. Rundblad, L. et al. Perceived sexual difficulties and sexual counseling in men and women across heart diagnoses: a nationwide cross-sectional study. J. Sex. Med. 14, 785–796 (2017).

    PubMed  Google Scholar 

  84. Steptoe, A., Jackson, S. E. & Wardle, J. Sexual activity and concerns in people with coronary heart disease from a population-based study. Heart 102, 1095–1099 (2016).

    PubMed  Google Scholar 

  85. Hoekstra, T. et al. Sexual problems in elderly male and female patients with heart failure. Heart 98, 1647–1652 (2012).

    PubMed  Google Scholar 

  86. Berg, S. K. et al. Sexual concerns and practices after ICD implantation: findings of the COPE-ICD rehabilitation trial. Eur. J. Cardiovasc. Nurs. 12, 468–474 (2013).

    PubMed  Google Scholar 

  87. Lukkarinen, H. & Lukkarinen, O. Sexual satisfaction among patients after coronary bypass surgery or percutaneous transluminal angioplasty: eight-year follow-up. Heart Lung 36, 262–269 (2007).

    PubMed  Google Scholar 

  88. Hasin, T. et al. Sexual function in patients supported with left ventricular assist device and with heart transplant. ESC. Heart Fail. 1, 103–109 (2014).

    PubMed  Google Scholar 

  89. Imprialos, K. P. et al. Sexual dysfunction, cardiovascular risk and effects of pharmacotherapy. Curr. Vasc. Pharmacol. 16, 130–142 (2018).

    CAS  PubMed  Google Scholar 

  90. Doumas, M. et al. Factors affecting the increased prevalence of erectile dysfunction in Greek hypertensive compared with normotensive subjects. J. Androl. 27, 469–477 (2006).

    PubMed  Google Scholar 

  91. Korhonen, P. E., Ettala, O., Kautiainen, H. & Kantola, I. Factors modifying the effect of blood pressure on erectile function. J. Hypertens. 33, 975–980 (2015).

    CAS  PubMed  Google Scholar 

  92. Ioakeimidis, N. et al. Association between office blood pressure, antihypertensive medication use and male sexual dysfunction: a penile Doppler study. Eur. Heart J. 41(Suppl. 2), ehaa946.2797 (2020).

    Google Scholar 

  93. Scranton, R. E., Goldstein, I. & Stecher, V. J. Erectile dysfunction diagnosis and treatment as a means to improve medication adherence and optimize comorbidity management. J. Sex. Med. 10, 551–561 (2013).

    CAS  PubMed  Google Scholar 

  94. Thomopoulos, C., Parati, G. & Zanchetti, A. Effects of blood-pressure-lowering treatment in hypertension: 9. Discontinuations for adverse events attributed to different classes of antihypertensive drugs: meta-analyses of randomized trials. J. Hypertens. 34, 1921–1932 (2016).

    CAS  PubMed  Google Scholar 

  95. Foy, C. G. et al. Blood pressure, sexual activity, and erectile function in hypertensive men: baseline findings from the systolic blood pressure intervention trial (SPRINT). J. Sex. Med. 16, 235–247 (2019).

    PubMed  PubMed Central  Google Scholar 

  96. Foy, C. G. et al. Effect of intensive vs standard blood pressure treatment upon erectile function in hypertensive men: findings from the Systolic Blood Pressure Intervention Trial. J. Sex. Med. 17, 238–248 (2020).

    CAS  PubMed  Google Scholar 

  97. Farmakis, I. T. et al. Effects of major antihypertensive drug classes on erectile function: a network meta-analysis. Cardiovasc. Drugs Ther. https://doi.org/10.1007/s10557-021-07197-9 (2021).

    Article  PubMed  Google Scholar 

  98. Silvestri, A. et al. Report of erectile dysfunction after therapy with beta-blockers is related to patient knowledge of side effects and is reversed by placebo. Eur. Heart J. 24, 1928–1932 (2003).

    CAS  PubMed  Google Scholar 

  99. Doumas, M. et al. Beneficial effects of switching from beta-blockers to nebivolol on the erectile function of hypertensive patients. Asian J. Androl. 8, 177–182 (2006).

    CAS  PubMed  Google Scholar 

  100. Baumhäkel, M., Schlimmer, N., Büyükafsar, K., Arikan, O. & Böhm, M. Nebivolol, but not metoprolol, improves endothelial function of the corpus cavernosum in apolipoprotein E-knockout mice. J. Pharmacol. Exp. Ther. 325, 818–823 (2008).

    PubMed  Google Scholar 

  101. Baumhäkel, M., Schlimmer, N. & Böhm, M., DO-IT Investigators. Effect of irbesartan on erectile function in patients with hypertension and metabolic syndrome. Int. J. Impot. Res. 20, 493–500 (2008).

    PubMed  Google Scholar 

  102. Kirby, R. S. et al. Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial. Urology 61, 119–126 (2003).

    PubMed  Google Scholar 

  103. McConnell, J. D. et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N. Engl. J. Med. 349, 2387–2398 (2003).

    CAS  PubMed  Google Scholar 

  104. Grimm, R. H. Jr. et al. Long-term effects on sexual function of five antihypertensive drugs and nutritional hygienic treatment in hypertensive men and women. Treatment of Mild Hypertension Study (TOMHS). Hypertension 29, 8–14 (1997).

    CAS  PubMed  Google Scholar 

  105. Nicolai, M. P. et al. A review of the positive and negative effects of cardiovascular drugs on sexual function: a proposed table for use in clinical practice. Neth. Heart J. 22, 11–19 (2014).

    CAS  PubMed  Google Scholar 

  106. Bruckert, E., Giral, P., Heshmati, H. M. & Turpin, G. Men treated with hypolipidaemic drugs complain more frequently of erectile dysfunction. J. Clin. Pharm. Ther. 21, 89–94 (1996).

    CAS  PubMed  Google Scholar 

  107. Elgendy, A. Y. et al. Statin use in men and new onset of erectile dysfunction: a systematic review and meta-analysis. Am. J. Med. 131, 387–394 (2018).

    PubMed  Google Scholar 

  108. Vlachopoulos, C. et al. Arterial function and intima-media thickness in hypertensive patients with erectile dysfunction. J. Hypertens. 26, 1829–1836 (2008).

    CAS  PubMed  Google Scholar 

  109. Gupta, S. et al. A possible mechanism for alteration of human erectile function by digoxin: inhibition of corpus cavernosum sodium/potassium adenosine triphosphatase activity. J. Urol. 159, 1529–1536 (1998).

    CAS  PubMed  Google Scholar 

  110. Lin, H. et al. Inhibitory effect of digoxin on testosterone secretion through mechanisms involving decreases of cyclic AMP production and cytochrome P450scc activity in rat testicular interstitial cells. Br. J. Pharmacol. 125, 1635–1640 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Hellenbart, E. L., Griffin, T. & DiDomenico, R. J. Beyond heart failure and ischemic heart disease: a scoping review of novel uses of ivabradine in adults. Pharmacotherapy 40, 544–564 (2020).

    PubMed  Google Scholar 

  112. Chen, L. W. & Yin, H. L. A literature review of antithrombotic and anticoagulating agents on sexual function. Andrologia 49, e12784 (2017).

    Google Scholar 

  113. Shiri, R. et al. Cardiovascular drug use and the incidence of erectile dysfunction. Int. J. Impot. Res. 19, 208–212 (2007).

    CAS  PubMed  Google Scholar 

  114. Corona, G. et al. Male and female sexual dysfunction in diabetic subjects: focus on new antihyperglycemic drugs. Rev. Endocr. Metab. Disord. 21, 57–65 (2020).

    PubMed  Google Scholar 

  115. Angelis, A. et al. The Mediterranean diet benefit on cardiovascular hemodynamics and erectile function in chronic heart failure male patients by decoding central and peripheral vessel rheology. Nutrients 13, 108 (2020).

    PubMed Central  Google Scholar 

  116. Gupta, B. P. et al. The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction: a systematic review and meta-analysis. Arch. Intern. Med. 171, 1797–1803 (2011).

    PubMed  Google Scholar 

  117. Allen, M. S. & Walter, E. E. Health-related lifestyle factors and sexual dysfunction: a meta-analysis of population-based research. J. Sex. Med. 15, 458–475 (2018).

    PubMed  Google Scholar 

  118. Steinke, E. E. et al. Sexual counselling for individuals with cardiovascular disease and their partners: a consensus document from the American Heart Association and the ESC Council on Cardiovascular Nursing and Allied Professions (CCNAP). Eur. Heart J. 34, 3217–3235 (2013).

    PubMed  Google Scholar 

  119. Nehra, A. et al. The Princeton III consensus recommendations for the management of erectile dysfunction and cardiovascular disease. Mayo Clin. Proc. 87, 766–778 (2012).

    PubMed  PubMed Central  Google Scholar 

  120. Chung, E. A review of current and emerging therapeutic options for erectile dysfunction. Med. Sci. 7, 91 (2019).

    CAS  Google Scholar 

  121. Kloner, R. A., Goldstein, I., Kirby, M. G., Parker, J. D. & Sadovsky, R. Cardiovascular safety of phosphodiesterase type 5 inhibitors after nearly 2 decades on the market. Sex. Med. Rev. 6, 583–594 (2018).

    PubMed  Google Scholar 

  122. Mittleman, M. A., Maclure, M. & Glasser, D. B. Evaluation of acute risk for myocardial infarction in men treated with sildenafil citrate. Am. J. Cardiol. 96, 443–446 (2005).

    CAS  PubMed  Google Scholar 

  123. Kloner, R. A. et al. A new perspective on the nitrate-phosphodiesterase type 5 inhibitor interaction. J. Cardiovasc. Pharmacol. Ther. 23, 375–386 (2018).

    CAS  PubMed  Google Scholar 

  124. Lowe, G. & Costabile, R. A. 10-Year analysis of adverse event reports to the Food and Drug Administration for phosphodiesterase type-5 inhibitors. J. Sex. Med. 9, 265–270 (2012).

    PubMed  Google Scholar 

  125. Barnes, H., Brown, Z., Burns, A. & Williams, T. Phosphodiesterase 5 inhibitors for pulmonary hypertension. Cochrane Database Syst. Rev. 1, CD012621 (2019).

    PubMed  Google Scholar 

  126. Redfield, M. M. et al. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA 309, 1268–1277 (2013).

    CAS  PubMed  Google Scholar 

  127. Vlachopoulos, C., Ioakeimidis, N., Rokkas, K. & Stefanadis, C. Cardiovascular effects of phosphodiesterase type 5 inhibitors. J. Sex. Med. 6, 658–674 (2009).

    CAS  PubMed  Google Scholar 

  128. Vlachopoulos, C. et al. Type 5 phosphodiesterase inhibition by sildenafil abrogates acute smoking-induced endothelial dysfunction. Am. J. Hypertens. 17, 1040–1044 (2004).

    CAS  PubMed  Google Scholar 

  129. Vlachopoulos, C., Hirata, K. & O’Rourke, M. F. Effect of sildenafil on arterial stiffness and wave reflection. Vasc. Med. 8, 243–248 (2003).

    PubMed  Google Scholar 

  130. Vlachopoulos, C. et al. Acute effect of sildenafil on inflammatory markers/mediators in patients with vasculogenic erectile dysfunction. Int. J. Cardiol. 182, 98–101 (2015).

    PubMed  Google Scholar 

  131. Hirata, K., Adji, A., Vlachopoulos, C. & O’Rourke, M. F. Effect of sildenafil on cardiac performance in patients with heart failure. Am. J. Cardiol. 96, 1436–1440 (2005).

    CAS  PubMed  Google Scholar 

  132. Hutchings, D. C., Anderson, S. G., Caldwell, J. L. & Trafford, A. W. Phosphodiesterase-5 inhibitors and the heart: compound cardioprotection? Heart 104, 1244–1250 (2018).

    CAS  PubMed  Google Scholar 

  133. Tzoumas, N., Farrah, T. E., Dhaun, N. & Webb, D. J. Established and emerging therapeutic uses of PDE type 5 inhibitors in cardiovascular disease. Br. J. Pharmacol. 177, 5467–5488 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Andersson, D. P. et al. Association between treatment for erectile dysfunction and death or cardiovascular outcomes after myocardial infarction. Heart 103, 1264–1270 (2017).

    PubMed  Google Scholar 

  135. Andersson, D. P. et al. Association of phosphodiesterase-5 inhibitors versus alprostadil with survival in men with coronary artery disease. J. Am. Coll. Cardiol. 77, 1535–1550 (2021).

    CAS  PubMed  Google Scholar 

  136. Anderson, S. G. et al. Phosphodiesterase type-5 inhibitor use in type 2 diabetes is associated with a reduction in all-cause mortality. Heart 102, 1750–1756 (2016).

    CAS  PubMed  Google Scholar 

  137. Hackett, G. et al. 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. 70, 244–253 (2016).

    CAS  PubMed  Google Scholar 

  138. Finkle, W. D. et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS ONE 9, e85805 (2014).

    PubMed  PubMed Central  Google Scholar 

  139. Gagliano-Juca, T. & Basaria, S. Testosterone replacement therapy and cardiovascular risk. Nat. Rev. Cardiol. 16, 555–574 (2019).

    PubMed  Google Scholar 

  140. Vlachopoulos, C. et al. Inverse association of total testosterone with central haemodynamics and left ventricular mass in hypertensive men. Atherosclerosis 250, 57–62 (2016).

    CAS  PubMed  Google Scholar 

  141. Vlachopoulos, C. et al. Testosterone deficiency: a determinant of aortic stiffness in men. Atherosclerosis 233, 278–283 (2014).

    CAS  PubMed  Google Scholar 

  142. Basaria, S. et al. Adverse events associated with testosterone administration. N. Engl. J. Med. 363, 109–122 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Budoff, M. J. et al. Testosterone treatment and coronary artery plaque volume in older men with low testosterone. JAMA 317, 708–716 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Basaria, S. et al. Effects of testosterone administration for 3 years on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels: a randomized clinical trial. JAMA 314, 570–581 (2015).

    CAS  PubMed  Google Scholar 

  145. Doumas, M., Viigimaa, M. & Papademetriou, V. Combined antihypertensive therapy and sexual dysfunction: terra incognita. Cardiology 125, 232–234 (2013).

    CAS  PubMed  Google Scholar 

  146. Blumentals, W. A., Gomez-Caminero, A., Joo, S. & Vannappagari, V. Is erectile dysfunction predictive of peripheral vascular disease? Aging Male 6, 217–221 (2003).

    CAS  PubMed  Google Scholar 

  147. Blumentals, W. A., Gomez-Caminero, A., Joo, S. & Vannappagari, V. Should erectile dysfunction be considered as a marker for acute myocardial infarction? Results from a retrospective cohort study. Int. J. Impot. Res. 16, 350–353 (2004).

    CAS  PubMed  Google Scholar 

  148. Schouten, B. W. et al. Erectile dysfunction prospectively associated with cardiovascular disease in the Dutch general population: results from the Krimpen study. Int. J. Impot. Res. 20, 92–99 (2008).

    CAS  PubMed  Google Scholar 

  149. Inman, B. A. et al. A population-based, longitudinal study of erectile dysfunction and future coronary artery disease. Mayo Clin. Proc. 84, 108–113 (2009).

    PubMed  PubMed Central  Google Scholar 

  150. Araujo, A. B. et al. Erectile dysfunction and mortality. J. Sex. Med. 6, 2445–2454 (2009).

    PubMed  PubMed Central  Google Scholar 

  151. Chung, S. D., Chen, Y. K., Lin, H. C. & Lin, H. C. Increased risk of stroke among men with erectile dysfunction: a nationwide population-based study. J. Sex. Med. 8, 240–246 (2011).

    PubMed  Google Scholar 

  152. Chung, R. Y. et al. Erectile dysfunction is associated with subsequent cardiovascular and respiratory mortality in cohort of 1,436 Chinese elderly men. J. Sex. Med. 12, 1568–1576 (2015).

    PubMed  Google Scholar 

  153. Loprinzi, P. D. & Nooe, A. Erectile dysfunction and mortality in a national prospective cohort study. J. Sex. Med. 12, 2130–2133 (2015).

    PubMed  Google Scholar 

  154. Uddin, S. M. I. et al. Erectile dysfunction as an independent predictor of future cardiovascular events: the multi-ethnic study of atherosclerosis. Circulation 138, 540–542 (2018).

    PubMed  Google Scholar 

  155. Frantzen, J., Speel, T. G., Kiemeney, L. A. & Meuleman, E. J. Cardiovascular risk among men seeking help for erectile dysfunction. Ann. Epidemiol. 16, 85–90 (2006).

    CAS  PubMed  Google Scholar 

  156. Speel, T. G., Kiemeney, L. A., Thien, T., Smits, P. & Meuleman, E. J. Long-term effect of inhibition of the angiotensin-converting enzyme (ACE) on cavernosal perfusion in men with atherosclerotic erectile dysfunction: a pilot study. J. Sex. Med. 2, 207–212 (2005).

    CAS  PubMed  Google Scholar 

  157. Brixius, K., Middeke, M., Lichtenthal, A., Jahn, E. & Schwinger, R. H. Nitric oxide, erectile dysfunction and beta-blocker treatment (MR NOED study): benefit of nebivolol versus metoprolol in hypertensive men. Clin. Exp. Pharmacol. Physiol. 34, 327–331 (2007).

    CAS  PubMed  Google Scholar 

  158. Cordero, A. et al. Erectile dysfunction in high-risk hypertensive patients treated with beta-blockade agents. Cardiovasc. Ther. 28, 15–22 (2010).

    CAS  PubMed  Google Scholar 

  159. Omvik, P. et al. Double-blind, parallel, comparative study on quality of life during treatment with amlodipine or enalapril in mild or moderate hypertensive patients: a multicentre study. J. Hypertens. 11, 103–113 (1993).

    CAS  PubMed  Google Scholar 

  160. Yang, L. et al. The effect of combined antihypertensive treatment (felodipine with either irbesartan or metoprolol) on erectile function: a randomized controlled trial. Cardiology 125, 235–241 (2013).

    CAS  PubMed  Google Scholar 

  161. Chang, S. W. et al. The impact of diuretic therapy on reported sexual function. Arch. Intern. Med. 151, 2402–2408 (1991).

    CAS  PubMed  Google Scholar 

  162. [No authors listed] MRC trial of treatment of mild hypertension: principal results. Medical research council working party. Br. Med. J. (Clin. Res. Ed.) 291, 97–104 (1985).

  163. Burgess, E. D. et al. Long-term safety and efficacy of the selective aldosterone blocker eplerenone in patients with essential hypertension. Clin. Ther. 25, 2388–2404 (2003).

    CAS  PubMed  Google Scholar 

  164. Parthasarathy, H. K. et al. A double-blind, randomized study comparing the antihypertensive effect of eplerenone and spironolactone in patients with hypertension and evidence of primary aldosteronism. J. Hypertens. 29, 980–990 (2011).

    CAS  PubMed  Google Scholar 

  165. Dadkhah, F. et al. Atorvastatin improves the response to sildenafil in hypercholesterolemic men with erectile dysfunction not initially responsive to sildenafil. Int. J. Impot. Res. 22, 51–60 (2010).

    CAS  PubMed  Google Scholar 

  166. Joseph, P. et al. Long-term effects of statins, blood pressure-lowering, and both on erectile function in persons at intermediate risk for cardiovascular disease: a substudy of the heart outcomes prevention evaluation-3 (HOPE-3) randomized controlled trial. Can. J. Cardiol. 34, 38–44 (2018).

    PubMed  Google Scholar 

  167. Trivedi, D. et al. Can simvastatin improve erectile function and health-related quality of life in men aged ≥40 years with erectile dysfunction? Results of the Erectile Dysfunction and Statins Trial [ISRCTN66772971]. BJU Int. 111, 324–333 (2013).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

All the authors researched data for the article. D.T.-P., N.I. and C.V. discussed the content of the article and wrote the manuscript. All the authors reviewed and edited the article before submission.

Corresponding author

Correspondence to Dimitrios Terentes-Printzios.

Ethics declarations

Competing interests

K.R. reports travel grants and honoraria from Bayer, Eli Lilly, Menarini and Pfizer. C.V. reports study and travel grants and honoraria from Bayer, Eli Lilly, Menarini and Pfizer. The other authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Cardiology thanks G. Corona, J. Hannan and M. Miner for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Vasculogenic ED

ED diagnosed using penile Doppler ultrasonography when the peak systolic velocity is <35 cm/s and/or when the end-diastolic velocity is >5 cm/s.

Vascular ageing biomarkers

Biomarkers that originate from changes in the function or structure of blood vessels with age, such as aortic stiffness, carotid intima–media thickness, coronary artery calcification and endothelial function.

Arterial stiffness

Reduced capacity of an artery to expand in response to changes in blood pressure.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Terentes-Printzios, D., Ioakeimidis, N., Rokkas, K. et al. Interactions between erectile dysfunction, cardiovascular disease and cardiovascular drugs. Nat Rev Cardiol 19, 59–74 (2022). https://doi.org/10.1038/s41569-021-00593-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41569-021-00593-6

  • Springer Nature Limited

This article is cited by

Navigation