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 I² statistics. A fixed-effect model was used if the heterogeneity was not significant (I² < 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.

Keywords: exercise capacity; heart failure; meta-analysis; randomized controlled trials; testosterone.