Testosterone and the Heart

Abstract

Testosterone (T) is the principal male sex hormone, secreted primarily by the testes and transported in the blood by the carrier protein, sex-hormone binding globulin (SHBG). Only 1% to 2% of testosterone circulates in blood as unbound "free" testosterone, but this fraction exhibits the most potent biological activity. Dihydrotestosterone (DHT), the most biologically active androgen, is synthesized from testosterone by 5a-reductase and exerts its effects via a family of androgen receptors. Some biological effects of testosterone may result from its aromatization to estradiol and subsequent interaction with the estrogen receptor. In addition to developing primary and secondary sex characteristics, androgens have diverse anabolic functions such as increasing muscle mass and bone density.1 Testosterone has also demonstrated a number of important effects on the cardiovascular system. In men, T levels begin to decrease after age 40, and this decrease has been associated with an increase in all-cause mortality and cardiovascular risk.2,3 However, whether low T causes negative cardiovascular events or is simply associated with them has yet to be determined. 4 This review highlights the evidence underlying the major interrelationships between androgens and the cardiovascular system. Testosterone Actions on Cardiovascular CellsTestosterone and the more potent DHT bind to cytoplasmic androgen receptors (AR) that are chaperoned by heat shock proteins. Once bound, the DHT-AR complex migrates to the nucleus, dimerizes with another DHT-AR complex, associates with coactivator proteins, and transactivates a family of genes with androgen response elements that alter myocardial and vascular cell behavior.1 Evidence also supports a direct rapid membrane effect of T on G-protein-coupled receptors, with an increase in inositol trisphosphate and diacylglycerol and subsequent alterations in cytoplasmic calcium and potassium channel activity. 5 Cardiovascular Risk in Testosterone Deficiency DefinitionTestosterone deficiency (TD) is a well-established major medical condition that negatively impacts male sexuality, general health, and quality of life. Symptoms include decreased libido, erectile dysfunction, decreased energy, depressed mood, irritability, and decreased sense of well-being. In the correct clinical setting, the diagnosis of TD is usually confirmed by low serum concentrations of total T (e.g., < 200 ng/mL) drawn in the early morning. However, there is no specific value that reliably distinguishes men who experience signs and symptoms of TD from those who do not nor those who will likely respond to treatment. Interpretation of total T concentrations is confounded by variation between individuals, variation in serum SHBG, and variation in androgen sensitivity. 6 Furthermore, considerable controversy has arisen regarding the accuracy of currently available commercial testosterone assays, especially those showing T levels at the lower end of the "normal" range. 4 Free testosterone level may be a more reliable indicator of androg...

Vascular Pathways of Testosterone: Clinical Implications

“…The most common cause of HF and impaired left ventricular dysfunction is coronary artery disease (CAD) with resulting cardiac ischemia, leading to decreased contractility and weakness of the heart muscle. It is common for men with HF to have low T levels and this leads to increased mortality [135] as they are associated with reduced heart function, loss of lean muscle mass and strength, chronic anaemia and insulin resistance [126]. Some studies have suggested that there also appears to be an inverse relationship between total and T-free levels and HF grade [69], in which case the prevalence of hypogonadism is greater than 40% [136].…”

Allostatic load and executive functions in overweight adults

“…The ups-and-downs 2 of testosterone are well known because, by one hand, it presents anti-inflammatory properties as 3 it exerts an inhibitory effect on adipocyte maturation (Bianchi, 2019). However, testosterone also 4 shows a strong link with cardiovascular diseases in ageing men (Goodale et al, 2017). In the same 5 way, it has been pointed out that estradiol might have protective effects on cognition (Luine, 2014).…”

“…This supplementary analysis is motivated due to the potential differences in how females and males 3 could react to chronic stress exposure. Briefly, and despite testosterone naturally has anti-4 inflammatory properties as it exerts an inhibitory effect on adipose tissue formation and maturation 5 (Bianchi, 2019), testosterone is also linked to greater incidence of cardiovascular diseases among 6 ageing males (Goodale et al, 2017). Equally, it has also been broadly discussed whether estradiol 7 might exert as a protective factor over cognition (Luine, 2014).…”

Conjugated Linoleic Acid Supplemented Diet Influences Serum Markers in Orchidectomized Sprague‐Dawley Rats

“…In addition, HS‐CRP concentrations also increased, which is an inflammatory marker associated with cardiac risk, especially myocardial infarction . The cardioprotective action of androgens may be exerted by acting directly on the cardiac muscle, triggering morphological and biochemical changes in the behaviour of vascular and myocardial cells; or indirectly by increasing the cardiovascular risk markers (atherogenic lipid profile, inflammation, obesity, diabetes mellitus, and atherosclerosis) . The CLA diet showed a cardioprotective action to prevent the increase in CK, LDH, and HS‐CRP concentrations caused by testosterone deficiency, although it did not change the CK‐MB concentration.…”