ORIGINAL RESEARCH
Testosterone Deficiency in Patients with Erectile Dysfunction: When Should a Higher Cardiovascular Risk Be Considered?

https://doi.org/10.1111/jsm.12596Get rights and content

Abstract

Introduction

Low testosterone levels (low T) increase the cardiovascular (CV) risk of men with erectile dysfunction (ED). T levels associated with a higher CV risk are unknown.

Aim

To determine the prevalence of CV risk factors associated with low T as defined by European Guidelines and their contribution to low T, overall and at different ages.

Methods

Multicenter, cross‐sectional, observational study conducted in Spain among men with ED aged ≥18 years visiting Urology/Andrology offices for sexual dysfunction. Anthropometric, clinical, and laboratory data, including total T (TT) values, were collected for 1,278 men.

Main Outcome Measures

Risk factors were assessed in men with TT ≤8, 8–12, and ≥12 nmol/L, and two‐group comparisons were made. Bivariate and multivariate logistic regression analyses were performed to calculate odds ratios for low T after adjusting for possible confounding factors.

Results

Mean age (standard deviation) was 58.0 (9.2) years. Age and prevalence of CV risk factors was similar in men with TT ≤8 nmol/L or 8–12 nmol/L and significantly higher than in men with TT >12 nmol/L. Low T was therefore considered as TT ≤12 nmol/L, with a prevalence of 33.3%. Obesity, hypertension, hyperlipidemia, and severe ED were the variables most strongly associated with low T: obesity in middle‐aged men; hyperlipidemia, and hypertension in older men. Severe ED was a risk factor in both groups. Hypolipidemic therapy had the greater effect in young men. Multivariate analysis showed that severe ED and obesity were the strongest predictors of low T.

Conclusion

T levels associated with increased CV risk could go as high as 12 nmol/L in men with ED, with distribution of risk factors showing differences according to age. Obesity and severe ED are the best predictors of low T‐related CV risk. Martínez‐Jabaloyas JM. Testosterone deficiency in patients with erectile dysfunction: when should a higher cardiovascular risk be considered? J Sex Med 2014;11:2083–2091.

Introduction

Erectile dysfunction (ED) is a common disorder in aging men affecting over 50% of men aged 40–70 years [1]. ED is frequently associated with modifiable risk factors such as diabetes, hypertension, hyperlipidemia, obesity, smoking, and a sedentary lifestyle 1, 2, 3, 4. ED has shown to increase the risk for cardiovascular (CV) events and all‐cause mortality, showing also a trend to increase the risk for CV mortality [5]. ED nearly doubles the risk for CV events in men with diabetes [6]. Men with ED are therefore advised to undergo a detailed medical assessment for early intervention on cardiovascular health 7, 8.

ED is one of the most common symptoms of testosterone deficiency syndrome (TDS), a condition associated with advancing age that is characterized by low levels of serum testosterone (low T) and the presence of compatible symptoms that are not specific of the condition 9, 10. The relationship between ED and low T has been recently reviewed [11].

Low T is thought to be associated with diabetes, metabolic syndrome (MetS), and CV disease [12]. A meta‐analysis of epidemiological data has shown that MetS is associated with lower levels of total T (TT) [13]. Longitudinal evidence has also shown that low T is associated with a higher risk for developing MetS, although it is unclear which is the cause and which is the consequence [14]. Some authors also support that low T might be a fundamental component of MetS [15].

Association between MetS and low T levels has shown to be more evident in men with ED [13], which may result in increased CV risk in these men. Comorbidities such as diabetes, hypertension, and obesity have been found to be associated with increased CV diseases in men with low T, independently of age [14]. Looking for low T among men with CV comorbidities and, conversely, identifying CV comorbidities when hypogonadism is found, is therefore of great importance [14].

Among symptoms associated with low T, ED is an important reason to seek medical advice. Most guidelines recommend the determination of serum T in men with ED signs 9, 10; however, a biochemical threshold for the definition of low T is still lacking, with differences among professional societies. Determining T thresholds may be of value as a reference to start testosterone replacement therapy (TRT) but also to adopt more intensive measures, beyond lifestyle modifications, to reduce CV risk. European Guidelines recommend TRT in men with ED and low T (defined as TT ≤8 nmol/L; 230 ng/dL) and also in those with “borderline” T levels (8–12 nmol/L) and a clinical picture of low T, where a short trial is advisable [9]. However, the T level associated with an increased CV risk in men with ED is unknown.

Section snippets

Aim

We analyzed the prevalence of common CV risk factors in a large cohort of men with ED with the aims of (i) analyzing which TT threshold, using the two thresholds proposed by European guidelines (8 and 12 nmol/L) as a reference, is associated with a higher prevalence of CV risk factors; and (ii) identifying which of these CV risk factors is associated with a higher likelihood for low T. The relative weight of each risk factor across the lifespan was also assessed.

Method

This was a multicenter, cross‐sectional, observational study conducted in Spain with the objective of assessing the relationship of ED and cardiovascular risk factors, including the prevalence of low T levels, among men seeking specialized medical attention due to sexual dysfunction. Patients aged ≥18 years were consecutively recruited by 394 urologists and andrologists from January to September 2009. Inclusion criteria included a diagnosis of ED according to the Erectile Function domain of the

Subjects' Characteristics

Participants were mainly white (98.4%), heterosexual (97.1%), with a stable partner (89.9%), with primary education, high school, or college degree (93.8%), and actively employed (64.5%). ED was diagnosed at the screening visit in 74.3% of subjects; a similar number of men (69%) had one or more comorbidities (hyperlipidemia, diabetes, or hypertension), with 46% of them having two or more comorbidities. Besides hypolipidemic therapy (16.7%), 36.9% of men were on antihypertensive therapy.

Testosterone Levels and Erectile Dysfunction

Discussion

Low T is known to be common among men consulting for ED [21]. Our study has revealed a prevalence of low T levels among men with ED ranging from 13.7% to 33.3% when thresholds are set at 8 or 12 nmol/L, respectively. Obesity and severe ED would be the strongest predictors of low T. In addition, we found that several CV risk factors that are commonly observed in men with ED 1, 2, 3, 4 are more prevalent not only in formal hypogonadic men according to European Guidelines [9], but also in those

Conclusion

T levels associated with increased CV risk could go as high as 12 nmol/L in men with ED, with distribution of risk factors showing differences according to age. Obesity and severe ED are the best predictors of low T‐related CV risk.

Conflict of Interest

José M. Martínez‐Jabaloyas is a scientific study/trial investigator for Bayer, Pfizer Inc, Lilly and GlaxoSmithKline.

Category 1

  • (a)

    Conception and Design

    José M. Martínez‐Jabaloyas

  • (b)

    Acquisition of Data

    José M. Martínez‐Jabaloyas

  • (c)

    Analysis and Interpretation of Data

    José M. Martínez‐Jabaloyas

Category 2

  • (a)

    Drafting the Article

    José M. Martínez‐Jabaloyas

  • (b)

    Revising It for Intellectual Content

    José M. Martínez‐Jabaloyas

Category 3

  • (a)

    Final Approval of the Completed Article

    José M. Martínez‐Jabaloyas

Acknowledgments

The author wishes to thank all members of the DE‐SDT study for their contribution. This research was supported by an unrestricted grant from Bayer Hispania SL. The authors wish to thank Beatriz Viejo, PhD, for her help in the writing of the manuscript and for her editorial support.

References (41)

  • T.S. Kóhler et al.

    Prevalence of androgen deficiency in men with erectile dysfunction

    Urology

    (2008)
  • R. Shabsigh et al.

    Health issues of men: Prevalence and correlates of erectile dysfunction

    J Urol

    (2005)
  • G. Corona 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)
  • G. Corona et al.

    Pulse pressure independently predicts major cardiovascular events in younger but not in older subjects with erectile dysfunction

    J Sex Med

    (2011)
  • G. Corona et al.

    Low levels of androgens in men with erectile dysfunction and obesity

    J Sex Med

    (2008)
  • G. Corona et al.

    NCEP‐ATPIII‐defined metabolic syndrome, type 2 diabetes mellitus, and prevalence of hypogonadism in male patients with sexual dysfunction

    J Sex Med

    (2007)
  • J. Buvat et al.

    Testosterone deficiency in men: Systematic review and standard operating procedures for diagnosis and treatment

    J Sex Med

    (2013)
  • R.C. Rosen et al.

    The multinational Men's Attitudes to Life Events and Sexuality (MALES) study: I. prevalence of erectile dysfunction and related health concerns in the general population

    Curr Med Res Opin

    (2004)
  • T. Yamada et al.

    Erectile dysfunction and cardiovascular events in diabetic men: A meta‐analysis of observational studies

    PLoS ONE

    (2012)
  • G. Jackson et al.

    Erectile dysfunction and coronary artery disease prediction: Evidence‐based guidance and consensus

    J Clin Pract

    (2010)
  • Cited by (0)

    View full text