Skip to main content

Advertisement

Log in

Testosterone and cardiovascular risk in patients with erectile dysfunction

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Background: The relationship between cardiovascular (CV) diseases (CVD) and testosterone (T) levels in men has not been completely clarified. Aim: To evaluate the association between T levels and CV risk in subjects with erectile dysfunction (ED) and to verify whether their body mass index might (BMI) represents a possible confounder in T-related CV stratification. Material and methods: A consecutive series of 2269 male patients attending the Outpatient Clinic for ED was studied. The assessment of CV risk was evaluated using the engine derived from the Progetto Cuore study. Results: After adjustment and for BMI and associated morbidities, SHBG-bound and -unbound T levels decreased as a function of CV risk assessed thorough Progetto Cuore risk engine. In addition, a higher prevalence of hypogonadism related symptoms and signs was associated with a higher CV risk. Among factors included in the Progetto Cuore risk engine age, total and HDL cholesterol and diabetes were all significantly associated with CV risk-dependent modification of total and calculated free-T levels. When the relationship between SHBG bound and unbound T and CV risk was evaluated as a function of obesity (BMI>30 kg/m2), all the aforementioned associations were confirmed only in non obese patients. Conclusions: Hypogonadism could be associated either with an increased or reduced CV risk, depending on the characteristics of subjects. Low T observed in obese patients might represent the result of higher CV risk rather than a direct pathogenetic mechanism.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Corona G, Rastrelli G, Vignozzi L, Mannucci E, Maggi M. Testoster-one, cardiovascular disease and the metabolic syndrome. Best Pract Res Clin Endocrinol Metab 2011, 25: 337–53.

    Article  PubMed  Google Scholar 

  2. Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med 2010, 363: 109–22.

    Article  PubMed Central  PubMed  Google Scholar 

  3. La Vignera S, Condorelli RA, Vicari E, D’Agata R, Calogero AE. New immunophenotype of blood endothelial progenitor cells and endothelial microparticles in patients with arterial erectile dysfunction and late-onset hypogonadism. J Androl 2011, 32: 509–17.

    Article  PubMed  Google Scholar 

  4. Lerner DJ, Kannel WB. Patterns of coronary heart disease morbidity and mortality in the sexes: a 26-year follow-up of the Framing-ham population. Am Heart J 1986, 111: 383–90.

    Article  PubMed  Google Scholar 

  5. Sullivan ML, Martinez CM, Gennis P, Gallagher EJ. The cardiac toxicity of anabolic steroids. Prog Cardiovasc Dis 1998, 41: 1–15.

    Article  PubMed  Google Scholar 

  6. Ruige JB, Mahmoud AM, De Bacquer D, Kaufman JM. Endogenous testosterone and cardiovascular disease in healthy men: a meta-analysis. Heart 2011, 97: 870–5.

    Article  PubMed  Google Scholar 

  7. Corona G, Monami M, Boddi V, et al. Low testosterone is associated with an increased risk of MACE lethality in subjects with erectile dysfunction. The J Sex Med 2010, 7: 1557–64.

    Article  Google Scholar 

  8. Tomlinson JW, Holden N, Hills RK, et al. Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group. Lancet 2001, 357: 425–31.

    Article  PubMed  Google Scholar 

  9. Bojesen A, Juul S, Birkebaek N & Gravholt CH. Increased mortality in Klinefelter syndrome. J Clin Endocrinol Metab 2004, 89: 3830–4.

    Article  PubMed  Google Scholar 

  10. Hamilton JB, Mestler GE. Mortality and survival: comparison of eunuchs with intact men and women in a mentally retarded population. J Gerontol 1969, 24: 395–411.

    Article  PubMed  Google Scholar 

  11. Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans. Arch Intern Med 2006, 166: 1660–5.

    Article  PubMed  Google Scholar 

  12. Akishita M, Hashimoto M, Ohike Y, et al. Low testosterone level as a predictor of cardiovascular events in Japanese men with coronary risk factors. Atherosclerosis 2010, 210: 232–6.

    Article  PubMed  Google Scholar 

  13. Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity asan independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation 1983, 67: 968–77.

    Article  PubMed  Google Scholar 

  14. Flegal KM, Graubard BI, Williamson DF, Gail MH. Cause-specific excess deaths associated with underweight, overweight, and obesity. JAMA 2007, 298: 2028–37.

    Article  PubMed  Google Scholar 

  15. Schulte H, Cullen P, Assmann G. Obesity, mortality and cardiovascular disease in the Münster Heart Study (PROCAM). Atherosclerosis 1999, 144: 199–209.

    Article  PubMed  Google Scholar 

  16. Corona G, Monami M, Boddi V, et al. Is obesity a further cardiovascular risk factor in patients with erectile dysfunction? J Sex Med 2010, 7: 2538–46.

    PubMed  Google Scholar 

  17. Corona G, Mannucci E, Fisher AD, et al. Low levels of androgens in men with erectile dysfunction and obesity. J Sex Med 2008, 5: 2454–63.

    PubMed  Google Scholar 

  18. Wu FC, Tajar A, Pye SR, et al; European Male Aging Study Group. Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab 2008, 93: 2737–45.

    Article  PubMed  Google Scholar 

  19. Petrone L, Mannucci E, Corona G, et al. Structured interview on erectile dysfunction (SIEDY): a new, multidimensional instrument for quantification of pathogenetic issues on erectile dysfunction. Int J Impot Res 2003, 15: 210–20.

    Article  PubMed  Google Scholar 

  20. Corona G, Jannini EA, Maggi M. Inventories for male and female sexual dysfunctions. Int J Impot Res 2006, 18: 236–50.

    Article  PubMed  Google Scholar 

  21. Corona G, Mannucci E, Petrone L, et al. ANDROTEST: a structured interview for the screening of hypogonadism in patients with sexual dysfunction. J Sex Med 2006, 3: 706–15.

    Article  PubMed  Google Scholar 

  22. Palmieri L, Panico S, Vanuzzo D, et al; Gruppo di Ricerca del Progetto CUORE. Evaluation of the global cardiovascular absolute risk: the Progetto CUORE individual score. Ann Ist Super Sanita 2004, 40: 393–9.

    PubMed  Google Scholar 

  23. McGregor JC, Kim PW, Perencevich EN, et al. Utility of the Chronic Disease Score and Charlson Comorbidity Index as comorbidity measures for use in epidemiologic studies of antibiotic-resistant organisms. Am J Epidemiol 2005, 161: 483–93.

    Article  PubMed  Google Scholar 

  24. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999, 84: 3666–72.

    Article  PubMed  Google Scholar 

  25. Corona G, Lee DM, Forti G, et al; EMAS Study Group. Age-related changes in general and sexual health in middle-aged and older men: results from the European Male Ageing Study (EMAS). J Sex Med 2010, 7: 1362–80.

    Article  PubMed  Google Scholar 

  26. Jannini EA, Screponi E, Carosa E, et al. Lack of sexual activity from erectile dysfunction is associated with a reversible reduction in serum testosterone. Int J Androl 1999, 22: 385–92.

    Article  PubMed  Google Scholar 

  27. Carosa E, Benvenga S, Trimarchi F, et al. Sexual inactivity results in reversible reduction of LH bioavailability. Int J Impot Res 2002, 14: 93–9.

    Article  PubMed  Google Scholar 

  28. Carosa E, Martini P, Brandetti F, et al. Type V phosphodiesterase inhibitor treatments for erectile dysfunction increase testosterone levels. Clin Endocrinol (Oxf) 2004, 61: 382–6.

    Article  Google Scholar 

  29. Corona G, Mannucci E, Lotti F, et al. Impairment of couple relationship in male patients with sexual dysfunction is associated with overt hypogonadism. J Sex Med 2009, 6: 2591–600.

    Article  PubMed  Google Scholar 

  30. Corona G, Rastrelli G, Monami M, et al. Body mass index regulates hypogonadism-associated CV risk: results from a cohort of subjects with erectile dysfunction. J Sex Med 2011, 8: 2098–105.

    Article  PubMed  Google Scholar 

  31. Bartalena L, Bogazzi F, Brogioni S, Grasso L, Martino E. Role of cytokines in the pathogenesis of the euthyroid sick syndrome. Eur J Endocrinol 1998, 138: 603–14.

    Article  PubMed  Google Scholar 

  32. Völzke H, Schwahn C, Wallaschofski H, Dörr M. Review: The association of thyroid dysfunction with all-cause and circulatory mortality: is there a causal relationship? J Clin Endocrinol Metab 2007, 92: 2421–9.

    Article  PubMed  Google Scholar 

  33. Corona G, Mannucci E, Petrone L, et al. Psychobiological correlates of smoking in patients with erectile dysfunction. Int J Impot Res 2005, 17: 527–34.

    Article  PubMed  Google Scholar 

  34. Giagulli VA, Kaufman JM, Vermeulen A. Pathogenesis of the decreased androgen levels in obese men. J Clin Endocrinol Metab 1994, 79: 997–1000.

    PubMed  Google Scholar 

  35. Vermeulen A, Kaufman JM, Deslypere JP, Thomas G. Attenuated luteinizing hormone (LH) pulse amplitude but normal LH pulse frequency, and its relation to plasma androgens in hypogonadism of obese men. J Clin Endocrinol Metab 1993, 76: 1140–6.

    PubMed  Google Scholar 

  36. Loves S, Ruinemans-Koerts J, de Boer H. Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism. Eur J Endocrinol 2008, 158: 741–7.

    Article  PubMed  Google Scholar 

  37. Corona G, Forti G, Maggi M. Why can patients with erectile dysfunction be considered lucky? The association with testosterone deficiency and metabolic syndrome. Aging Male 2008, 11: 193–9.

    Article  PubMed  Google Scholar 

  38. Corona G, Mannucci E, Forti G, Maggi M. Hypogonadism, ED, metabolic syndrome and obesity: a pathological link supporting cardiovascular diseases. Int J Androl 2009, 32: 587–98.

    Article  PubMed  Google Scholar 

  39. Corona G, Mannucci E, Fisher AD, et al. Low levels of androgens in men with erectile dysfunction and obesity. J Sex Med 2008, 5: 2454–63.

    PubMed  Google Scholar 

  40. Corona G, Rastrelli G, Morelli A, Vignozzi L, Mannucci E, Maggi M. Hypogonadism and metabolic syndrome. J Endocrinol Invest 2011, 34: 557–67.

    PubMed  Google Scholar 

  41. Corona G, Monami M, Rastrelli G, et al. Type 2 diabetes mellitus and testosterone: a meta-analysis study. Int J Androl 2011, 34: 528–40.

    Article  PubMed  Google Scholar 

  42. Ding EL, Song Y, Malik VS, Liu S. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 2006, 295: 1288–99.

    Article  PubMed  Google Scholar 

  43. Feng Y, Zhu Y, Chen X, Sha J, Fan L, Chen Q. Effects of diet-induced hypercholesterolemia on testosterone-regulated protein expression in mice liver. J Nanosci Nanotechnol 2005, 5: 1273–6.

    Article  PubMed  Google Scholar 

  44. Martínez-Martos JM, Arrazola M, Mayas MD, Carrera-González MP, García MJ, Ramírez-Expósito MJ. Diet-induced hypercholesterolemia impaired testicular steroidogenesis in mice through the renin-angiotensin system. Gen Comp Endocrinol 2011, 173: 15–9.

    Article  PubMed  Google Scholar 

  45. Ploumidou K, Kyroudi-Voulgari A, Perea D, Anastasiou I, Mitropoulos D. Effect of a hypercholesterolemic diet on serum lipid profile, plasma sex steroid levels, and prostate structure in rats. Urology 2010, 76: 1517.e1–5.

    Article  Google Scholar 

  46. Kaplan SA, Lin J, Johnson-Levonas AO, Shah AK, Meehan AG. Increased occurrence of marked elevations of lipoprotein(a) in ageing, hypercholesterolaemic men with low testosterone. Aging Male 2010, 13: 40–3.

    Article  PubMed  Google Scholar 

  47. Chearskul S, Charoenlarp K, Thongtang V, Nitiyanant W. Study of plasma hormones and lipids in healthy elderly Thais compared to patients with chronic diseases: diabetes mellitus, essential hypertension and coronary heart disease. J Med Assoc Thai 2000, 83: 266–77.

    PubMed  Google Scholar 

  48. Ponholzer A, Madersbacher S, Rauchenwald M, Jungwirth S, Fischer P, Tragl KH. Vascular risk factors and their association to serum androgen levels in a population-based cohort of 75-year-old men over 5 years: results of the VITA study. World J Urol 2010, 28: 209–14.

    Article  PubMed  Google Scholar 

  49. Stanworth RD, Kapoor D, Channer KS, Jones TH. Statin therapy is associated with lower total but not bioavailable or free testosterone in men with type 2 diabetes. Diabetes Care 2009, 32: 541–6.

    Article  PubMed Central  PubMed  Google Scholar 

  50. Corona G, Boddi V, Balercia G, et al. The effect of statin therapy on testosterone levels in subjects consulting for erectile dysfunction. J Sex Med 2010, 7: 1547–56.

    Article  PubMed  Google Scholar 

  51. Isidori AM, Giannetta E, Greco EA, et al. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol (Oxf) 2005, 63: 280–93.

    Article  Google Scholar 

  52. Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab 2004, 89: 3313–8.

    Article  PubMed  Google Scholar 

  53. Kapoor D, Goodwin E, Channer KS, Jones TH. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol 2006, 154: 899–906.

    Article  PubMed  Google Scholar 

  54. Hughes GS, Mathur RS, Margolius HS. Sex steroid hormones are altered in essential hypertension. J Hypertens 1989, 7: 181–7.

    Article  PubMed  Google Scholar 

  55. Svartberg J, von Mühlen D, Schirmer H, Barrett-Connor E, Sundfjord J, Jorde R. Association of endogenous testosterone with blood pressure and left ventricular mass in men. The Tromsø Study. Eur J Endocrinol 2004, 150: 65–71.

    Article  PubMed  Google Scholar 

  56. Labropoulos B, Velonakis E, Oekonomakos P, Laskaris J, Katsimades D. Serum sex hormones in patients with coronary disease and their relationship to known factors causing atherosclerosis. Cardiology 1982, 69: 98–103.

    Article  PubMed  Google Scholar 

  57. Corona G, Mannucci E, Lotti F, et al. Pulse pressure, an index of arterial stiffness, is associated with androgen deficiency and impaired penile blood flow in men with ED. J Sex Med 2009, 6: 285–9.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. Maggi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Corona, G., Rastrelli, G., Balercia, G. et al. Testosterone and cardiovascular risk in patients with erectile dysfunction. J Endocrinol Invest 35, 809–816 (2012). https://doi.org/10.3275/8063

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.3275/8063

Key-words

Navigation