Effect of testosterone treatment on cardiac biomarkers in a randomized controlled trial of men with type 2 diabetes

The Endocrine Society's 97th Annual Meeting & Expo (ENDO 2015)EJ Gianatti, R Hoermann, Q Lam, P Dupuis, JD Zajac, M Grossmann | March 06, 2015

Summary: In men with type 2 diabetes (T2D), researchers conducted this randomized, double-blind, parallel, placebo-controlled study to assess the effect of testosterone treatment on cardiac biomarkers. Testosterone treatment reduced N-terminal pro B-type natriuretic peptide (NT-proBNP), they concluded, but did not change high-sensitivity cardiac troponin T (hs-cTnT). They called for further studies to determine whether men with increased cardiac biomarkers prior to testosterone therapy are at higher risk of testosterone-treatment associated adverse cardiac events.

Methods:

  • Researchers included men aged 35-70 years with T2D and a total testosterone level <12.0 nmol/L (346 ng/dl) at high risk of cardiovascular events, median 10-year United Kingdom Prospective Diabetes Study (UKPDS) coronary heart disease (CHD) risk 21% (IQR 16%, 27%).
  • They randomly assigned 88 participants to 40 weeks of intramuscular testosterone undecanoate (n= 45) or matching placebo (n=43).
  • Main outcome measures included NT-proBNP and hs-cTnT.

Results:

  • Researchers observed that testosterone treatment reduced NT-proBNP (mean adjusted difference (MAD) in change over 40 weeks across the testosterone and placebo groups, -17.9 ng/L (95% CI -32.4, -3.5; P=0.047), but did not change hs-cTnT (MAD, 0.41 ng/L [95% CI -0.56, 1.39; P=0.62]).
  • In total, 6 men (3 in the testosterone, and 3 in the placebo group) experienced an adverse cardiac event (P=1.00).
  • Testosterone-treated men who experienced a cardiovascular event had higher baseline NT-proBNP (p=0.004) and hs-cTnT levels (P=0.01) as compared with men who did not.
  • At baseline, 10-year UKPDS CHD risk was associated positively with NT-proBNP (tau=0.21, P=0.004) and hs-cTnT (tau=0.23, P=0.003), and inversely with testosterone (total testosterone tau=-0.18, P=0.02, calculated free testosterone tau=-0.19, P=0.01), but there was no significant association between testosterone and cardiac biomarkers (P>0.05).

This is an investigator initiated research trial with funding and trial medications provided by Bayer Healthcare.  Bayer Healthcare was not involved in design, conduct or analysis of this trial. EG was supported by NHMRC Postgraduate Fellowship (#1018196), CVL Research Grant Pfizer Australia (#CR05.09), RACP/Osteoporosis Australia Research Entry Grant and University of Melbourne Postgraduate Scholarship. PD was supported by Bourse du CMDP (Comité des Médecins, Dentistes et Pharmaciens) du CHUQ (Centre Hospitalier Universitaire de Québec) et de la Fondation du CHUQ - CMDP 2011-2012. MG was supported by an NHMRC Career Development Fellowship (#1024139).