Author + information
- Viktor Čulić, MD, PhD∗ ()
- ↵∗Department of Cardiology, University Hospital Center Split, Šoltanska 1, 21000 Split, Croatia
The role of testosterone in health and disease has become the subject of widely increasing interest. Kloner et al. (1) reviewed the basic endocrinology and pathophysiologic mechanisms that may link low levels of endogenous testosterone to cardiovascular disease in men. They mentioned that testosterone, by reducing peripheral vascular resistance, may increase cardiac output and lower left ventricular end-diastolic pressure. However, they overlooked clinical and experimental data suggesting mechanisms of the influence of testosterone on left ventricular diastolic function.
Several recent studies have linked circulating testosterone levels with echocardiographic parameters of the left ventricular diastolic dysfunction (DD). In asymptomatic men with type 2 diabetes mellitus, lower free testosterone within the normal range has been associated with DD independent of other cardiovascular risk factors (2). Also in male patients with type 2 diabetes with no structural heart disease, low total testosterone has been associated with a higher left ventricular filling pressure and more dire parameters of diastolic function (3). Last, we have reported that circulating levels of total testosterone are related inversely to the severity of DD, but only among patients without previous myocardial infarction (4).
Several mechanisms have been implicated in the association between testosterone and DD (5). In normal rat hearts, testosterone inhibited cardiac fibroblast migration and proliferation, and myofibroblast differentiation induced by transforming growth factor-β1. Additionally, the antifibrotic effect of testosterone may be the modulation of cell signaling and response of cardiac fibroblasts through a decreased production of collagen after stimulation by transforming growth factor-β1 and angiotensin II. Furthermore, androgens may provide protection from the toxicity of oxidative stress, another stimulus for cardiac fibroblast proliferation through increased production of transforming growth factor-β1. In contrast to these putative favorable effects, exogenous testosterone showed adverse effects on myocardial remodeling and worsened cardiac dysfunction after myocardial infarction in both sexes in a rat model (5).
These examples of clinical and experimental observations are in line with the hypothesis that testosterone poses beneficial biological effects on relatively normal hearts without a significant pathologic cardiovascular burden or process, whereas in hearts already affected by pathologic myocardial remodeling, testosterone may be associated with adverse effects (5). However, there is a need for further clarification of the role of testosterone on the left ventricular diastolic function, particularly concerning oxidative, proliferative, and fibrotic processes in the myocardium, both with normal aging and under conditions such as diabetes mellitus, myocardial infarction, or other pathologic stimuli or structural heart disease.
Please note: Dr. Čulić has reported that he has no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation