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Men with erectile dysfunction and low testosterone levels have an increased risk of dying from cardiovascular disease

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Citation: Low testosterone is associated with an increased risk of MACE lethality in subjects with erectile dysfunction. Corona G, Monami M, Boddi V, et al. J Sex Med 2010;7(4 Pt 1):1557-1564.

A consecutive series of 1687 patients attending an andrology clinic for erectile dysfunction (ED) was followed for a mean of 4.3 ± 2.6 years to investigate whether low testosterone levels predict incident fatal or nonfatal major adverse cardiovascular events (MACE) in men with ED. Patients in this prospective cohort study were interviewed using the structured interview on erectile dysfunction (SIEDY) and the ANDROTEST structured interview to measure aspects of ED and hypogonadal-related symptoms. Total testosterone was evaluated at baseline and information on MACE was obtained from registry database records.1

Key Points

The nested case-control study showed:

  • At baseline, over 20% of men were hypogonadal, according to a widely accepted lower limit for normal total testosterone levels1
  • Hypogonadism ranged from 5.2% to 13.8% and 22.4% depending on the threshold used (total testosterone less than 8, 10.4 and 12 nmol/L, respectively*)1
  • During follow-up, 139 of the patients had a major cardiac event, such as ischaemic heart disease, cerebrovascular events (stroke or transient ischaemic attack) or peripheral artery disease1
  • MACE were fatal in 15 men1
  • Although low testosterone in itself was not associated with MACE, those patients with total testosterone levels below 10.4 nmol/L who had a major cardiac event were significantly more likely to die than those with higher testosterone levels1
  • When adjusted for Chronic Diseases Score (an index of comorbidities) the risk of death was increased by a factor of seven (hazard ratio [HR] 7.1) in men with testosterone below 8 nmol/L1
  • Of interest, fatal MACE were associated with a higher ANDROTEST score measuring hypogonadal-related symptoms and signs (HR = 1.2 for each ANDROTEST score increment; P = 0.05).1

What is known

There is an increasing body of evidence to indicate that ED may be an early surrogate marker of a number of disease states, such as hypertension, metabolic syndrome, diabetes mellitus, depression and coronary heart disease.2-6This suggests that a referral for ED provides a good opportunity to screen for comorbidities. Hypogonadism is an accepted contributor to ED, and testosterone replacement therapy has been shown to benefit sexual function and improve the efficacy of phosphodiesterase type 5 inhibitor therapy for ED.3,7,8 Recent European consensus guidelines recognize that men with total testosterone levels below 8 nmol/L will usually benefit from testosterone replacement therapy; additional investigation is recommended for men with levels between 8 and 12 nmol/L.9 Although there are suggestions that testosterone is a protective factor against the development of atherosclerosis,10 there is very sparse data on the effects of low testosterone and the incidence of MACE, particularly in men with ED

This study is the first to investigate whether low testosterone levels in men with ED predicts incident fatal or nonfatal MACE.

What this study adds

The study provides evidence that low testosterone levels are associated with a significantly higher mortality from MACE in men with erectile dysfunction. The identification of low testosterone levels should therefore alert the clinician to the possibility of increased risk of dying from a cardiovascular event.

Dr Giovanni Corona from the University of Florence, who led the research team, said that, although the findings need to be confirmed by larger studies, “…this is the first time that low testosterone has been associated with higher death rates from heart disease in men with erectile dysfunction. Our work shows that screening for testosterone deficiency in men with erectile dysfunction may help clinicians identify those at higher risk from cardiovascular events. However, at the moment we can't say whether low testosterone levels are the cause or the consequence of this higher risk.” While screening the testosterone levels of men with ED may be a worthwhile way of identifying those at most risk from heart disease, the numbers affected will be small, and large-scale studies are needed to look at whether testosterone replacement therapy in at-risk men can help prevent unnecessary deaths from cardiovascular disease.1


*8, 10.4 and 12 nmol/L = 230, 300 and 350 ng/dL, respectively.


References

1. Corona G, Monami M, Boddi V, et al. Low testosterone is associated with an increased risk of MACE lethality in subjects with erectile dysfunction. J Sex Med 2010;7(4 Pt 1):1557-1564.
2. Jackson G. Prevention of cardiovascular disease by the early identification of erectile dysfunction. Int J Impot Res 2008;20 Suppl 2:S9-14.
3. 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(4):193-199.
4. Montorsi P, Ravagnani PM, Galli S, et al. Association between erectile dysfunction and coronary artery disease: Matching the right target with the right test in the right patient. Eur Urol 2006;50(4):721-731.
5. Corona G, Fagioli G, Mannucci E, et al. Penile doppler ultrasound in patients with erectile dysfunction (ED): role of peak systolic velocity measured in the flaccid state in predicting arteriogenic ED and silent coronary artery disease. J Sex Med 2008;5(11):2623-2634.
6. Ma RC, So WY, Yang X, et al. Erectile dysfunction predicts coronary heart disease in type 2 diabetes. J Am Coll Cardiol 2008;51(21):2045-2050.
7. Maggi M, Schulman C, Quinton R, et al. The burden of testosterone deficiency syndrome in adult men: economic and quality-of-life impact. J Sex Med 2007;4(4 Pt 1):1056-1069.
8. Isidori AM, Giannetta E, Gianfrilli D, et al. Effects of testosterone on sexual function in men: results of a meta-analysis. Clin Endocrinol (Oxf) 2005;63(4):381-394.
9. Wang C, Nieschlag E, Swerdloff R, et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. Eur Urol 2009;55(1):121-130.
10. Malkin CJ, Pugh PJ, Jones RD, et al. Testosterone as a protective factor against atherosclerosis--immunomodulation and influence upon plaque development and stability. J Endocrinol 2003;178(3):373-380.

Last updated: 2018
G.MKT.GM.MH.01.2018.0500