The role of testosterone in cardiovascular health
Testosterone and the cardiovascular system: a comprehensive review of the clinical literature. Mesbah Oskui P, French W, Herring M, et al. J Am Heart Assoc 2013; 2: e000272
This summary gives an overview of a comprehensive review of studies that have examined the association between testosterone levels and cardiovascular health.1 The review focuses on the role of testosterone in cardiovascular diseases, including the incidence of coronary artery disease (CAD), congestive heart failure (CHF), and heart-rate-corrected QT (QTc) length prolongation. The role of testosterone on risk factors for atherosclerosis, including type 2 diabetes mellitus (T2DM), obesity, and inflammation, are also reviewed. Findings from studies that investigated the use of testosterone therapy on cardiovascular diseases in men with testosterone deficiency (TD) are summarized and possible mechanisms of action (MoA) for testosterone with respect to these outcomes are discussed.
What is known
Despite an increasing incidence of hypogonadism in the USA,34 the relationship between testosterone levels and cardiovascular health is not fully understood. Low levels of testosterone are associated with comorbidities known to increase cardiovascular mortality, such as T2DM and obesity.23 In a meta-analysis of seven population-based studies, low levels of testosterone showed a trend towards an association with increased cardiovascular mortality.35 Although statistical significance was not attained, the study showed that a decrease of 2.1 standard deviations in total testosterone levels was associated with a 25% increase in cardiovascular mortality risk. Two further studies have analyzed the association between testosterone and cardiovascular mortality.36,37 Menke et al. showed that a reduction of testosterone levels from the 90th to the 10th percentile correlated with a significant increase in cardiovascular mortality.36 In agreement with Menke et al., Malkin et al. demonstrated that levels of bioavailable testosterone > 2.6 nmol/L were associated with improved survival from vascular mortality (death from atherosclerosis, heart failure, or cardiac arrest) in 930 men with CAD.37 The association between testosterone and cardiovascular diseases is well documented; however, the exact mechanisms behind this are currently unknown. Further investigation is required to fully elucidate the MoA of testosterone in the cardiovascular system and develop further treatment targets.
What this study adds
A comprehensive review of the clinical literature shows that patients with CAD,2,3 CHF,11 T2DM,14,15 and obesity23 have low testosterone levels. Furthermore, levels of testosterone in hypogonadal men were associated with the severity of CAD2,3 and CHF.11 testosterone therapy in hypogonadal men improves a number of cardiovascular health factors. In hypogonadal men with CAD, testosterone therapy improved exercise-induced 1-mm ST-segment depression,4,5 a measure of myocardial ischemia, and vasodilation and coronary artery blood flow.6 In patients with CHF, testosterone therapy significantly improved components of exercise capacity, a fundamental feature of CHF.12 Furthermore, testosterone therapy improved a number of risk factors for atherosclerosis, including T2DM,15,17-21 obesity,15,20 and QTc length.32 Overall, these findings suggest that testosterone plays an important role in the cardiovascular system and maintaining cardiovascular health.
The exact mechanisms of testosterone that influence the cardiovascular system are not yet fully elucidated. Conflicting evidence for possible underlying mechanisms are from experimental in-vitro, animal, and pilot studies, such as Angelova et al.22 This highlights how in-vitro studies play a key role in determining the positive effects of testosterone on the cardiovascular system. Despite the growing evidence for the important role of testosterone on the cardiovascular system, the Endocrine Society guidelines make no recommendations for screening of hypogonadism in patients with heart disease.38 Furthermore, using testosterone therapy in patients with heart disease to improve survival is not recommended. As such, longitudinal, placebo-controlled, randomized trials of testosterone therapy in hypogonadal men are warranted to understand the role of testosterone in cardiovascular diseases.