Testosterone Supplementation in Patients With Chronic Heart Failure: A Meta-Analysis of Randomized Controlled Trials

Abstract

Background: The effect of testosterone supplementation in patients with chronic heart failure (CHF) remains uncertain.Methods: A meta-analysis of randomized controlled trials (RCTs) was performed. RCTs that evaluate the chronic effect of testosterone supplementation on exercise capacity and cardiac function in CHF were identified via searching of PubMed, Embase, and the Cochrane's Library databases. Heterogeneity was evaluated by the Cochrane's Q test and I 2 statistics. A fixed-effect model was used if the heterogeneity was not significant (I 2 < 50%); otherwise, a random-effect model was applied.Results: Eight studies including 170 patients in the testosterone supplementation group and 162 in the control group were included. Overall, testosterone supplementation was not associated with an improved exercise capacity (walking test: standardized mean difference [SMD] = 0.36, p = 0.07). Sensitivity analyses limited to male patients showed similar results (SMD = 0.21, p = 0.15), and subgroup analyses also showed similar results in male HF patients with baseline total testosterone (TT) ≥ or < 10 nmol/L. However, patients with TT at endpoint ≥ 25 nmol/L was associated with improved exercise capacity (SMD = 1.12, p = 0.02), but not for those with TT at endpoint < 25 nmol/L (SMD = 0.24, p = 0.12). In addition, VO 2max (weight mean difference [WMD] = 0.85, p = 0.43), the functional classification (the New York Heart Association classification: WMD = −0.08, p = 0.16) and quality of life (Minnesota Living with Heart Failure [MLHF] questionnaire: WMD = −6.03, p = 0.12) were not significantly affected. Moreover, testosterone supplementation did not significantly affect left ventricular ejection fraction (WMD: −1.52%, p = 0.37), serum B-type natriuretic peptide (SMD: −0.19, p = 0.23), or a composite outcome of death or HF hospitalization (risk ratio [RR]: 1.02, p = 0.96). Although testosterone supplementation increased systolic blood pressure (BP) in CHF patients (WMD: 5.68 mmHg, p < 0.001), diastolic BP or heart rate was not significantly changed as compared to control.Conclusions: Testosterone supplementation within a physiological range is not associated with significantly improved exercise capacity, cardiac function, quality of life, or clinical outcome in CHF patients.

Late‐onset hypogonadism: Reductio ad absurdum of the cardiovascular risk‐benefit of testosterone replacement therapy

“…A 2012 meta‐analysis of randomized controlled trials strengthened the evidence of a beneficial effect of T treatment on exercise capacity and oxygen consumption in patients with CHF 164 . However, a more recent meta‐analysis showed that TRT did not improve the exercise capacity, cardiac function, quality of life, or clinical outcome of patients with CHF 165 . Taken together, current EAA guidelines recommend against the use of TRT in patients with severe CHF given the risk of polycythemia and VTE in a frail population 33 …”

“…164 However, a more recent meta-analysis showed that TRT did not improve the exercise capacity, cardiac function, quality of life, or clinical outcome of patients with CHF. 165 Taken together, current EAA guidelines recommend against the use of TRT in patients with severe CHF given the risk of polycythemia and VTE in a frail population. 33 Impaired skeletal muscle function and muscle atrophy are features of CHF that could be related to the state of chronic inflammation and insulin resistance characterizing these patients.…”

The Illusory Case for Treatment of an Invented Disease

“…In the absence of pathologic hypogonadism, clinical studies of safety for testosterone treatment for cardiovascular events [including heart failure ( 74 ) or venous thromboembolism ( 75 , 76 )] are reported as either observational cohorts ( 75 , 77 – 81 ) or meta-analyses of short-term placebo-controlled randomized clinical trials ( 74 , 77 , 82 – 90 ). The former lack cogency due to the intractable confounding of cardiovascular disease mechanisms with numerous risk factors having comparable or greater influence than testosterone as well as the inability of observational data alone to justify interventional treatment.…”

Cardiovascular risk and testosterone – from subclinical atherosclerosis to lipoprotein function to heart failure

“…Opposite conclusions were, however, reported in a updated meta-analysis showing that in FH patients, testosterone supplementation within a physiological dose-range does not improve exercise tolerance (shuttle walk test or the six-minute walk test), cardiac function, quality of life, or clinical outcome. Of note, a subgroup analysis highlighted that subjects who had reached testosterone levels ≥ 25 nmol/L benefitted the most in terms of improved exercise capacity, as evaluated by shuttle walk test or the six-minute walk test [ 138 ].…”