Effect of Exercise Training and Testosterone Replacement on Skeletal Muscle Wasting in Patients With Heart Failure With Testosterone Deficiency

Santos, Marcelo Rodrigues dos; Sayegh, Ana Luiza Carrari; Bacurau, Aline Villa Nova; Arap, Marco Antônio; Brum, Patrícia Chakur; Pereira, Rosa Maria Rodrigues; Takayama, Liliam; Barretto, Antônio Carlos Pereira; Negräo, Carlos Eduardo; Alves, Maria Janieire de Nazaré Nunes

doi:10.1016/j.mayocp.2016.02.014

Cited by 52 publications

(49 citation statements)

References 34 publications

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“…Testosterone treatment improved insulin resistance and glucose metabolism, increased total body mass, and decreased FM [36] . The reported increase in disability, comorbidities, and death rates among frail older individuals with testosterone deficiency warrants providing testosterone treatment to attenuate the impact of sarcopenia, to reduce disability, and to increase functional independence.…”

Section: Discussionmentioning

confidence: 94%

“…Testosterone treatment brings about a significant increase in muscle strength in older men. More importantly, it is compelling that men with heart failure had significant improvements with testosterone treatment in a multitude of physical functions [36] . As shown by Hyde et al [10] and Krasnoff et al [11] , low free testosterone was independently associated with frailty and worsening of mobility limitations in older men.…”

Section: Discussionmentioning

confidence: 99%

“…The reported increase in disability, comorbidities, and death rates among frail older individuals with testosterone deficiency warrants providing testosterone treatment to attenuate the impact of sarcopenia, to reduce disability, and to increase functional independence. Testosterone treatment coupled with exercise in patients with and those without heart failure showed improvements in LBM and functional capacity [17,36] . This suggests that testosterone treatment with exercise attenuates muscle sympathetic hyperactivity and muscle wasting, thus improving functional capacity in hypogonadal patients with heart failure.…”

Section: Discussionmentioning

confidence: 99%

“…Testosterone treatment contributes to significant increases in muscle mass and strength in older men, especially in those with heart failure [36] . The frailty index (a composite of a large number of components representing signs, symptoms, and functional impairments that accumulate with age) is significantly associated with lower total testosterone, free testosterone, and DHEAS levels even after adjustment for confounders such as BMI and age.…”

Section: Effects Of Testosterone Deficiency and Testosterone Treatmenmentioning

confidence: 99%

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Testosterone Deficiency and Testosterone Treatment in Older Men

et al. 2016

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Frailty is a clinical condition related to changes in metabolism, to sarcopenia, and to decline in muscle mass and strength, bone mineral density, and physical function with aging. The pathophysiology of frailty is multifactorial and associated with comorbidities. Testosterone is implicated in regulating metabolic functions, maintenance of muscle and bone, and inhibition of adipogenesis. In older individuals, reduced testosterone is thought to contribute to an altered state of metabolism, loss of muscle and bone, and increased fat, leading to sarcopenia, sarcopenic obesity, and frailty. While no direct relationship between testosterone deficiency (commonly known as hypogonadism) and frailty has been established (due to the multifactorial nature of frailty), clinical evidence suggests that testosterone deficiency is associated with increased sarcopenia and obesity. Testosterone treatment in frail older men with limited mobility and with testosterone deficiency improved insulin resistance, glucose metabolism, and body composition. These changes contribute to better physical function and improved quality of life. Because frailty increases disability, comorbidities, and the risk of hospitalization, institutionalization, and mortality in older men, it is warranted to explore the potential usefulness of testosterone treatment in frail men with hypogonadism in order to attenuate the progression of sarcopenia and frailty. In this paper, we will discuss the impact of testosterone deficiency on frailty and the potential role of testosterone treatment in ameliorating and reducing the progression of frailty. Such an approach may reduce disability and the risk of hospitalization and increase functional independence and quality of life.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Effects Of Testosterone Deficiency and Testosterone Treatmenmentioning

confidence: 99%

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Testosterone Deficiency and Testosterone Treatment in Older Men

et al. 2016

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“…Given emerging evidence from basic-science models, it is reasonable to assume that TRT positively affects the exercise capacity of CHF patients via a peripheral mechanism, such as promoting increased type I muscle fiber proliferation. 27 Four authors have investigated the effects of TRT on exercise capacity in men with CHF. Toma et al performed a meta-analysis of these studies and discovered that there was a net pooled improvement of 0.52 standard deviations in exercise capacity among those who received TRT.…”

Section: Congestive Heart Failurementioning

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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