Vitamin D supplementation does not prevent the testosterone decline in males with advanced heart failure: the EVITA trial

PurposeObservational studies indicate a positive association between circulating 25-hydroxyvitamin D (25OHD) and testosterone (T) concentrations. Because low 25OHD concentrations and T deficiency are considered to be a generalized phenomenon in patients with advanced heart failure (HF), we aimed to investigate whether vitamin D supplementation has beneficial effects on T indices in these patients.MethodsIn a pre-specified secondary analysis of the EVITA (effect of vitamin D on mortality in heart failure) randomized controlled trial, we analyzed in male subjects with 25OHD concentrations<75nmol/L the effect of a daily vitamin D-3 supplement of 4000IU for 3years (n=71) vs. placebo (n=62) on total T (TT), sex hormone-binding globulin (SHBG), free T (fT), and bioactive T (BAT). We assessed changes from baseline until study termination and between-group differences at study termination.Results25OHD increased in the placebo group from 36.6nmol/L by 9.2nmol/L (95% CI 3.2-15.1nmol/L; P=0.003) and in the vitamin D group from 36.5nmol/L by 63.9nmol/L (95% CI 52.6-75.3nmol/L; P<0.001), with a significant between-group difference at study termination (P<0.001). TT and SHBG concentrations did not change significantly, neither in the placebo group nor in the vitamin D group (P=0.845-0.082), but concentrations of fT and BAT declined significantly in both groups (P=0.025-0.008). At study termination, there were no between-group differences in TT (P=0.612), SHBG (P=0.393), fT (P=0.861), or BAT (P=0.960).ConclusionsIn male patients with advanced HF and low 25OHD concentrations, a daily vitamin D-3 supplement of 4000IU for 3years did not prevent the decline in testosterone indices.