Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anabolic steroids are synthetic derivatives of testosterone that were developed as adjunct therapy for a variety of medical conditions. Today they are most commonly used to enhance athletic performance and muscular development. Both illicit and medically indicated anabolic steroid use have been temporally associated with many subsequent defects within each of the body systems. Testosterone is the preferred ligand of the human androgen receptor in the myocardium and directly modulates transcription, translation, and enzyme function. Consequent alterations of cellular pathology and organ physiology are similar to those seen with heart failure and cardiomyopathy. Hypertension, ventricular remodeling, myocardial ischemia, and sudden cardiac death have each been temporally and causally associated with anabolic steroid use in humans. These effects persist long after use has been discontinued and have significant impact on subsequent morbidity and mortality. The mechanisms of cardiac disease as a result of anabolic steroid use are discussed in this review.
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PMID:The cardiac toxicity of anabolic steroids. 971 56

The effects of testosterone on cardiac electrophysiology are poorly described. In this study we report the effect of physiologic testosterone therapy in 2 cohorts of men, the first with stable coronary disease and the second with congestive heart failure. Testosterone reduced QT dispersion in the heart failure cohort; no other effects were observed.
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PMID:Effect of testosterone therapy on QT dispersion in men with heart failure. 1460 11

Recent clinical studies have reported that testosterone therapy reduces myocardial ischaemia in men with coronary artery disease, and the beneficial modulation of coronary vascular tone by testosterone has been proposed as an effector mechanism. Maintenance of a correct response to vasoconstrictive and vasodilatory agents is essential in the control of vascular tone. Endothelial dysfunction, most commonly manifested through an elevation in vascular tone, is implicated as an initiating factor in conditions such as hypertension and atherosclerosis. Increased sensitivity to vasoconstrictive stimuli is also proposed in the development of heart failure and hypertensive vascular remodelling, while increased coronary vascular reactivity to vasoconstrictive factors is likely further to restrict coronary blood flow through the partially occluded atherosclerotic vessel. Reduced vasodilatation and enhanced vasoconstriction can also lead to vasospasm and exacerbation of anginal symptoms. Testosterone is well known to elicit direct vasodilatation, but its influence upon responses induced by other vasoactive agents is less coherent, and may depend upon the underlying pathogenic process or gender. The aim of this review is to present the data obtained from both the patient and animal studies conducted to date, to ascertain any influence testosterone may have upon the regulation of vascular tone.
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PMID:The influence of testosterone upon vascular reactivity. 1524 19

Physiological testosterone therapy increases exercise capacity and reduces symptom scores in men with chronic heart failure (CHF). Tumour necrosis factor-alpha (TNF-alpha) exerts a significant pathologic activity in CHF, and physiologic testosterone replacement therapy is associated with reduced serum levels of TNF-alpha in hypogonadal men with concomitant coronary artery disease. It is unknown whether testosterone exerts a similar immunomodulatory action in men with CHF. Testosterone therapy administered in three placebo-controlled studies, for either 6 hours (two 30-mg buccal tablets, n=12) or 3 months (fortnightly 100 mg intra muscular injection, n=20; or daily 5 mg transdermally, n=62). The effects of testosterone were also assessed on lipopolysaccharide (LPS)-induced TNF- production in whole blood obtained from 27 men with CHF. Incubation with testosterone (10 nM, 1 M, and 100 M) resulted in a reduction in LPS-induced TNF- production from 12.6 +/- 1.3 to 11.2 +/- 1.1 (P = 0.053), 10.3 +/- 1.1 (P = 0.0046), and 9.2 +/- 1.1 (P = 0.000066) ng/ml, respectively. However in men with CHF, serum levels of TNF- were similar before and after treatment with testosterone or placebo, irrespective of the length of study or route of administration. The clinically beneficial actions of testosterone in men with CHF are unlikely to be mediated by reducing TNF-alpha.
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PMID:Physiologic testosterone therapy has no effect on serum levels of tumour necrosis factor-alpha in men with chronic heart failure. 1643 47

Testosterone is reported to have an acute vasodilating action in vitro, an effect that may impart a favourable haemodynamic response in patients with chronic heart failure. However, the effect of chronic testosterone exposure on general vascular reactivity is poorly described. In the present study, fresh subcutaneous resistance arteries were obtained from patients with heart failure (n=10), healthy controls (n=9) and men with androgen-deficiency (n=17). All arteries were studied using a wire myograph to examine the effect of cumulative additions of testosterone (1 nmol/l-100 micromol/l) compared with vehicle control following maximal pre-constriction with KCl (1-100 micromol/l). The vascular reactivity of arteries from androgen-deficient patients was examined further by recording tension concentration curves to cumulative additions of noradrenaline (1 nmol/l-100 micromol/l) and U46619 (1-300 nmol/l), followed by relaxation concentration curves to additions of ACh (acetylcholine; 10 nmol/l-30 micromol/l) and SNP (sodium nitroprusside; 10 nmol-30 micromol/l) respectively. In all cases, statistical analysis was performed by ANOVA. Patients with proven androgen-deficiency were treated according to clinical recommendations for a minimum of 3 months and further arteries (n=19) were taken for experimentation using the same protocol. In all groups, testosterone was confirmed to be an acute concentration-dependent vasodilator at concentrations > or =1 micromol/l (P=0.0001). The dilating effect of testosterone was augmented in patients with androgen-deficiency prior to treatment, and this effect was abrogated following appropriate testosterone replacement. Testosterone therapy significantly reduced the normal vascular dilating response to ACh and SNP (P<0.01) and significantly increased the contractile response to noradrenaline (P<0.01), but not U46619. Testosterone is an acute dose-dependent vasodilator of resistance arteries. Physiological testosterone replacement attenuates general vascular reactivity in androgen-deficient subjects. The numerous perceived benefits of testosterone replacement may be offset by a decline in vascular reactivity and, therefore, further studies and careful monitoring of patients is recommended.
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PMID:Effect of testosterone on ex vivo vascular reactivity in man. 1668 61

Resistance to insulin occurs in chronic heart failure (CHF) and is related to prognosis. Studies of testosterone in non-(CHF) males suggest that physiological testosterone therapy improves insulin sensitivity. This was a single-blind placebo controlled crossover trial to determine the effect of testosterone replacement on insulin sensitivity in 13 men with moderate to severe CHF (ejection fraction 30.5+/-1.3). The primary outcome was the homeostatic model index (HOMA-IR) of fasting insulin sensitivity and secondary outcomes were body composition as measured by bioelectrical impedance and glucose tolerance to a standard 75 g oral glucose load. Analysis was performed on the delta values with the treatment effect of placebo compared with that of testosterone. At baseline HOMA-IR correlated with measures of body fat [% fat mass (rP=0.84, p=0.0001) and body mass index (rP=0.79, p=0.01)] but not with CHF severity. Testosterone reduced HOMA-IR (-1.9+/-0.8, p=0.03) indicating improved fasting insulin sensitivity. Testosterone also increased total mass (+1.5+/-0.5 kg, p=0.008) and decreased body fat (-0.8+/-0.3%, p=0.02). Testosterone improves fasting insulin sensitivity in men with CHF and may also increase lean body mass, these data suggest a favourable effect of testosterone on an important metabolic component of CHF.
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PMID:The effect of testosterone on insulin sensitivity in men with heart failure. 1702 36

Increased longevity and population aging will increase the number of men with relative testosterone deficiency, as systemic levels of testosterone decrease by about 1% each year. Androgen deficiency should only be diagnosed in men with definite signs and symptoms, accompanied by low total testosterone levels measured in the morning by a reliable assay. Although clinical trials data are limited, current practice guidelines recommend testosterone replacement therapy for symptomatic men with low testosterone levels to improve bone mineral density, muscle mass and strength, sexual function, and quality of life. Testosterone replacement is not recommended for all older men with low testosterone levels, and should be avoided in patients with prostate or breast cancer, hyperviscosity, erythrocytosis, untreated obstructive sleep apnea, or severe heart failure. The goal of all available testosterone treatment modalities (intramuscular injections, nongenital patch or gel, bioadhesive buccal and oral testosterone, and pellets) is to achieve serum testosterone levels in the mid-normal range during treatment. Cost varies widely among these preparations and may limit their use. Patients receiving testosterone replacement therapy should be re-evaluated 3 months after testosterone initiation and at least annually thereafter.
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PMID:Considerations for the diagnosis and treatment of testosterone deficiency in elderly men. 1790 50

Testosterone (T) has been shown to cause vasodilation in rabbit coronary arteries through a nongenomic pathway. Part of this T-induced relaxation was shown to be mediated by opening voltage dependent K(+) channels. T infusion also reduces peripheral resistance in human males with heart failure. The effects of T or its active metabolite 5-alpha dihydrotestosterone (DHT) are not well studied. This study investigates the effect of T and DHT on contraction in guinea pig gallbladder strips. T or DHT induced a concentration-dependent relaxation of cholecystokinin octapeptide (CCK)-induced tension. Pretreatment of the strips with PKA inhibitor 14-22 amide myristolated had no significant effect on the relaxation induced by either T or DHT. Pretreatment of strips with 2-APB, an inhibitor of IP(3) induced Ca(2+) release, produced a significant (p<0.001) reduction in the T- or DHT-induced relaxation. Bisindolymaleimide IV and chelerythrine Cl(-) when used in combination had no significant effect on the amount of CCK-induced tension, but significantly (p<0.01) decreased the amount of T- or DHT-induced relaxation. The flavone chrysin, an aromatase inhibitor, and genistein, an isoflavone, each produced a significant (p<0.01) reduction in CCK-induced tension. Chrysin significantly (p<0.05) increased T-induced relaxation; however, genistein had no effect on T-induced relaxation. It is concluded that T and DHT inhibits gallbladder motility rapidly by nongenomic actions of the hormones. Multiple pathways that include inhibition of intracellular Ca(2+) release, inhibition of extracellular Ca(2+) entry, and the actions of PKC may mediate this effect.
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PMID:Testosterone and dihydrotestosterone inhibit gallbladder motility through multiple signalling pathways. 1858 91

Chronic heart failure is common and can be described as a syndrome characterized by impairment of cardiac function associated with a maladaptive metabolic and neurohormonal axis. The thesis that testosterone replacement therapy may be helpful as a treatment for chronic heart failure may seem at first to be unlikely. Testosterone therapy is widely believed to be deleterious to the cardiovascular system and there is a common misconception that the excess of ischaemic heart disease in young and middle-aged males compared to females is a direct effect of endogenous serum testosterone levels. In this chapter we will present the published evidence of the effects of endogenous and therapeutic testosterone on the heart and the human cardiovascular system with an emphasis on the pathologic syndrome of chronic heart failure. There is developing evidence that of all morbid populations, patients with chronic heart failure in particular are likely to benefit from testosterone treatment since the natural history is that of progressive disordered metabolism with catabolic excess and androgen imbalance.
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PMID:Testosterone in chronic heart failure. 1901 Dec 97

Male gender is a major risk factor for premature cardiovascular death, a relationship not yet explained. Low testosterone in men is a risk factor for the metabolic syndrome and type 2 diabetes and is associated independently with individual components of the metabolic syndrome--visceral obesity, insulin resistance, hyperglycemia, hypertension and dyslipidemia. Epidemiological studies report increased mortality in men with low testosterone. Testosterone replacement in the short-term reduces waist circumference, cholesterol and circulating pro-inflammatory cytokines and improves insulin sensitivity and glycemic control in diabetics. Testosterone also has beneficial effects on cardiac ischemia, angina and chronic heart failure. This manuscript reviews the current evidence supporting a link between low testosterone and cardiovascular disease, highlighting the need for larger, longer-term studies.
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PMID:Testosterone deficiency: a risk factor for cardiovascular disease? 2038 74


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