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

  • Armin Zittermann
  • Jana B. Ernst
  • Sylvana Prokop
  • Uwe Fuchs
  • Jens Dreier
  • Joachim Kuhn
  • Cornelius Knabbe
  • Heiner K. Berthold
  • Ioanna Gouni-Berthold
  • Jan F. Gummert
  • Jochen Börgermann
  • Stefan Pilz
Original Contribution



Observational 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.


In 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 < 75 nmol/L the effect of a daily vitamin D3 supplement of 4000 IU for 3 years (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.


25OHD increased in the placebo group from 36.6 nmol/L by 9.2 nmol/L (95% CI 3.2–15.1 nmol/L; P = 0.003) and in the vitamin D group from 36.5 nmol/L by 63.9 nmol/L (95% CI 52.6–75.3 nmol/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).


In male patients with advanced HF and low 25OHD concentrations, a daily vitamin D3 supplement of 4000 IU for 3 years did not prevent the decline in testosterone indices.


Vitamin D Testosterone Free testosterone Bioactive testosterone Sex hormone Heart failure Randomized controlled trial 



The study was sponsored by the Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Germany. The Friede Springer Herz Stiftung (Berlin, Germany) and Merck KGaA (Darmstadt, Germany, EMR200109-616) provided funding for the study. Merck KGaA also provided the study medication and DiaSorin (Dietzenbach, Germany) provided the 25OHD test kits. The funding sources were not involved in the study design, collection, analysis, or interpretation of data, or in preparation or submission of the manuscript for publication. We thank Birgit Drawe and Bärbel Kammel, Institute for Laboratory and Transfusion Medicine, Heart- and Diabetes Center NRW, Ruhr-University of Bochum, Bad Oeynhausen, Germany, for their excellent technical assistance.

Compliance with ethical standards

Conflict of interest

Armin Zittermann has received speaker honoraria from DiaSorin, Germany. Jana B. Ernst, Sylvana Prokop, Uwe Fuchs, Jens Dreier, Joachim Kuhn, Heiner K Berthold, Ioanna Gouni-Berthold, Jan F. Gummert, Jochen Börgermann, and Stefan Pilz declare that they have no conflict of interest.

Supplementary material

394_2018_1666_MOESM1_ESM.doc (56 kb)
Supplementary material 1 (DOC 55 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Armin Zittermann
    • 1
  • Jana B. Ernst
    • 1
  • Sylvana Prokop
    • 1
  • Uwe Fuchs
    • 1
  • Jens Dreier
    • 2
  • Joachim Kuhn
    • 2
  • Cornelius Knabbe
    • 2
  • Heiner K. Berthold
    • 3
  • Ioanna Gouni-Berthold
    • 4
  • Jan F. Gummert
    • 1
  • Jochen Börgermann
    • 1
  • Stefan Pilz
    • 5
  1. 1.Clinic for Thoracic and Cardiovascular SurgeryHerz- und Diabeteszentrum NRWBad OeynhausenGermany
  2. 2.Institute for Laboratory and Transfusion MedicineHerz- und Diabeteszentrum NRW, Ruhr University BochumBad OeynhausenGermany
  3. 3.Department of Internal Medicine and GeriatricsBethel Clinic (EvKB)BielefeldGermany
  4. 4.Polyclinic for Endocrinology, Diabetes and Preventive Medicine (PEDP)University of CologneCologneGermany
  5. 5.Division of Endocrinology and Diabetology, Department of Internal MedicineMedical University of GrazGrazAustria

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