Testosterone and the Cardiovascular System: A Comprehensive Review of the Clinical Literature

Oskui, Peyman Mesbah; French, William J.; Herring, Michael J.; Mayeda, Guy S.; Burstein, Steven; Kloner, Robert A.

doi:10.1161/jaha.113.000272

Cited by 191 publications

(175 citation statements)

References 166 publications

(304 reference statements)

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“…Moreover, diastolic dysfunction was found in patients with type 2 diabetes with low testosterone level compared with similar patients with normal testosterone levels (Tinetti et al 2015). Furthermore, patients suffering from congestive heart failure (Jankowska et al 2006) and coronary artery disease (Li et al 2012) have been shown to have lower levels of testosterone compared with healthy men, and the severity of these conditions had a strong correlation with the degree of testosterone deficiency (Li et al 2012, Oskui et al 2013. Recent clinical studies demonstrated that testosterone replacement could improve insulin sensitivity, increase lean mass, and decrease subcutaneous fat (Dhindsa et al 2016) and also improve cardiometabolic parameters in type 2 diabetes men with testosterone deprivation (Hackett et al 2014) and in hypogonadal men with metabolic syndrome (Saad et al 2016).…”

Section: Metabolic Disturbancementioning

confidence: 99%

“…This state can be found in aging male individuals. The prevalence of testosterone deficiency increases substantially with age (Araujo et al 2007) and is associated with the development of several disorders including obesity, dyslipidemia, insulin resistance, metabolic syndrome, and cardiovascular disease (Grossmann et al 2008, Oskui et al 2013. Moreover, testosterone deprivation alone significantly induces left ventricular (LV) contractile dysfunction and cardiac sympathovagal imbalance in orchiectomized rats (Pongkan et al 2015).…”

Section: Introductionmentioning

confidence: 99%

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Testosterone deprivation accelerates cardiac dysfunction in obese male rats

Pongkan

Pintana

Sivasinprasasn

et al. 2016

Journal of Endocrinology

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Low testosterone level is associated with increased risks of cardiovascular diseases. As obese-insulin-resistant condition could impair cardiac function and that the incidence of obesity is increased in aging men, a condition of testosterone deprivation could aggravate the cardiac dysfunction in obese-insulin-resistant subjects. However, the mechanism underlying this adverse effect is unclear. This study investigated the effects of obesity on metabolic parameters, heart rate variability (HRV), left ventricular (LV) function, and cardiac mitochondrial function in testosterone-deprived rats. Orchiectomized or sham-operated male Wistar rats (n=36per group) were randomly divided into groups and were given either a normal diet (ND, 19.77% of energy fat) or a high-fat diet (HFD, 57.60% of energy fat) for 12weeks. Metabolic parameters, HRV, LV function, and cardiac mitochondrial function were determined at 4, 8, and 12weeks after starting each feeding program. We found that insulin resistance was observed after 8weeks of the consumption of a HFD in both sham (HFS) and orchiectomized (HFO) rats. Neither the ND sham (NDS) group nor ND orchiectomized (NDO) rats developed insulin resistance. The development of depressed HRV, LV contractile dysfunction, and increased cardiac mitochondrial reactive oxygen species production was observed earlier in orchiectomized (NDO and HFO) rats at week 4, whereas HFS rats exhibited these impairments later at week 8. These findings suggest that testosterone deprivation accelerates the impairment of cardiac autonomic regulation and LV function via increased oxidative stress and impaired cardiac mitochondrial function in obese-orchiectomized male rats.

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Section: Metabolic Disturbancementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Testosterone deprivation accelerates cardiac dysfunction in obese male rats

Pongkan

Pintana

Sivasinprasasn

et al. 2016

Journal of Endocrinology

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“…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.…”

Section: The Endocrinology Of Testosteronementioning

confidence: 99%

Testosterone and the Heart

Goodale

Sadhu

Petak

et al. 2017

Methodist DeBakey Cardiovascular Journal

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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...

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“…Many studies have shown the protective role of estrogen considering cardiovascular system in women during reproductive age (11,12), while lately there are many studies indicating that the testosterone deficiency is related to the outbreak of cardiovascular risk factors (13). It is well known that sex hormones are involved in adipocyte metabolism and fat distribution (14).…”

mentioning

confidence: 99%

Sex-related Differences in Correlation of Overweight/Obesity Markers to Blood Pressure in Prepubertal Children in Osijek-Baranja County – a Cross-sectional Study

Rašić

Zrinušić²,

Drenjančević³

2017

Per Biol

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Background:The aim was to assess prevalence of overweight/obesity and evaluate their relations to blood pressure and blood glucose concentrations in prepubertal school children. Design and method: Third grade elementary school children were included (total 111-53 girls, 58 boys; 9±1 years). Height, weight, body mass index (BMI), waist circumference (WC), upper arm and thigh skin fold (ASF, TSF) and systolic (SBP) and diastolic blood pressure (DBP) and fasting blood glucose concentrations (fBGC) were measured.Results: 13.51% subjects were overweight (BMI>85th percentile; 3 girls and 12 boys) and 15.32% subjects were obese (BMI>95th percentile;7 girls and 10 boys). Boys had significantly higher SBP than girls. Overweight/obese boys had significantly thicker ASF and TSF, higher SB, higher DBP (and higher fBGC compared to normal-weight boys; 5 boys and 4 girls were hypertensive (SBP>95th percentile). In boys, there were significant positive correlations of BMI and WC with SBP, DBP, ASF and TSF. Overweight/ obese girls had significantly thicker ASF and TSF and greater WC compared to normal-weight girls. SBP, DBP or fBGC were not significantly different between OW/OB and normal-weight girls. In girls, BMI and WC significantly positively correlated with ASF and TSF, but no correlations to BP were observed. WC positively correlated to fBGC in both, boys and girls. Conclusions: Significant association of OW/OB to arterial BP levels in prepubertal boys and a lack of associations among OW/OB markers and arterial BP levels in girls suggest that OW/OB might not be as important risk factors in development of hypertension in adulthood in females as in males.IntroductIon O verweight and obesity in children, young adults and adults becomes problem nationwide (1). Many recent studies showed that the childhood obesity is a global issue: in 77% of the countries examined, at least 10% of youth were overweight and in 20% of the countries at least 3% of children were obese (2). In these studies, adiposity status is assessed in the clinical setting using simple anthropometric measures such as the body mass index (BMI) and waist circumference (WC). While BMI is a common measure, nowadays criticized as not descriptive enough in children, waist circumference is showing its' utility in iden- (8,9,10). This gives the opportunity to prevent or alleviate risks of developing cardiovascular diseases in adulthood.It is well known that sex hormones have influence on cardiovascular risk factors. Many studies have shown the protective role of estrogen considering cardiovascular system in women during reproductive age (11,12), while lately there are many studies indicating that the testosterone deficiency is related to the outbreak of cardiovascular risk factors (13). It is well known that sex hormones are involved in adipocyte metabolism and fat distribution (14). Estrogen has anabolic effect on fat, especially subcutaneous fat. Decrease in estrogen levels in menopausal women is associated with the loss of subcutaneous fat and increas...

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Testosterone and the Cardiovascular System: A Comprehensive Review of the Clinical Literature

Cited by 191 publications

References 166 publications

Testosterone deprivation accelerates cardiac dysfunction in obese male rats

Testosterone deprivation accelerates cardiac dysfunction in obese male rats

Testosterone and the Heart

Sex-related Differences in Correlation of Overweight/Obesity Markers to Blood Pressure in Prepubertal Children in Osijek-Baranja County – a Cross-sectional Study

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