title: Effect of testosterone treatment on cardiac biomarkers in a randomized controlled trial of men with type 2 diabetes.
abstract: OBJECTIVE
  To assess the effect of testosterone treatment on cardiac biomarkers in men with type 2 diabetes (T2D).
  
  
  METHODS
  Randomized double-blind, parallel, placebo-controlled trial.
  
  
  METHODS
  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%). Eighty-eight participants were randomly assigned to 40 weeks of intramuscular testosterone undecanoate (n = 45) or matching placebo (n = 43).
  
  
  METHODS
  N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT).
  
  
  RESULTS
  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). Six men, three in each group experienced an adverse cardiac event, displaying already higher baseline NT-proBNP (P < 0·01) and hs-cTnT levels (P = 0·01). At baseline, 10-year UKPDS CHD risk was associated positively with NT-proBNP (τ = 0·21, P = 0·004) and hs-cTnT (τ = 0·23, P = 0·003) and inversely with testosterone (total testosterone τ = -0·18, P = 0·02, calculated free testosterone τ = -0·19, P = 0·01), but there was no significant association between testosterone and cardiac biomarkers (P > 0·05).
  
  
  CONCLUSIONS
  In this trial of men with T2D and high cardiovascular risk, testosterone treatment reduced NT-proBNP and did not change hs-cTnT. Further studies should determine whether men with increased cardiac biomarkers prior to testosterone therapy are at higher risk of testosterone treatment-associated adverse cardiac events.
authors.affiliation: Department of Medicine Austin Health, Austin Health, University of Melbourne, Heidelberg, Vic., Australia.|Endocrine Unit, Austin Health, University of Melbourne, Heidelberg, Vic., Australia.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Gianatti
authors.affiliation: Department of Medicine Austin Health, Austin Health, University of Melbourne, Heidelberg, Vic., Australia.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Hoermann
authors.affiliation: Department of Biochemistry, Austin Health, University of Melbourne, Heidelberg, Vic., Australia.
authors.forename: Que
authors.initials: Q
authors.lastname: Lam
authors.affiliation: Department of Medicine Austin Health, Austin Health, University of Melbourne, Heidelberg, Vic., Australia.|Endocrine Unit, Austin Health, University of Melbourne, Heidelberg, Vic., Australia.
authors.forename: Philippe
authors.initials: P
authors.lastname: Dupuis
authors.affiliation: Department of Medicine Austin Health, Austin Health, University of Melbourne, Heidelberg, Vic., Australia.|Endocrine Unit, Austin Health, University of Melbourne, Heidelberg, Vic., Australia.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Zajac
authors.affiliation: Department of Medicine Austin Health, Austin Health, University of Melbourne, Heidelberg, Vic., Australia.|Endocrine Unit, Austin Health, University of Melbourne, Heidelberg, Vic., Australia.
authors.forename: Mathis
authors.initials: M
authors.lastname: Grossmann
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D003327:Coronary Disease / Q000097:blood / Q000150:complications / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D010446:Peptide Fragments / Q000097:blood; D011446:Prospective Studies; D012307:Risk Factors; D013739:Testosterone / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D013997:Time Factors; D020107:Troponin T / Q000097:blood; D006113:United Kingdom
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D013739:Testosterone; C010792:testosterone undecanoate