Biomarkers and Noncalcified Coronary Artery Plaque Progression in Older Men Treated With Testosterone

J Clin Endocrinol Metab. 2020 Jul 1;105(7):2142-2149. doi: 10.1210/clinem/dgz242.


Objective: Recent results from the Cardiovascular Trial of the Testosterone Trials showed that testosterone treatment of older men with low testosterone was associated with greater progression of noncalcified plaque (NCP). We evaluated the effect of anthropometric measures and cardiovascular biomarkers on plaque progression in individuals in the Testosterone Trial.

Methods: The Cardiovascular part of the trial included 170 men aged 65 years or older with low testosterone. Participants received testosterone gel or placebo gel for 12 months. The primary outcome was change in NCP volume from baseline to 12 months, as determined by coronary computed tomography angiography (CCTA). We assayed several markers of cardiovascular risk and analyzed each marker individually in a model as predictive variables and change in NCP as the dependent variable.

Results: Of 170 enrollees, 138 (73 testosterone, 65 placebo) completed the study and were available for the primary analysis. Of 10 markers evaluated, none showed a significant association with the change in NCP volume, but a significant interaction between treatment assignment and waist-hip ratio (WHR) (P = 0.0014) indicated that this variable impacted the testosterone effect on NCP volume. The statistical model indicated that for every 0.1 change in the WHR, the testosterone-induced 12-month change in NCP volume increased by 26.96 mm3 (95% confidence interval, 7.72-46.20).

Conclusion: Among older men with low testosterone treated for 1 year, greater WHR was associated with greater NCP progression, as measured by CCTA. Other biomarkers and anthropometric measures did not show statistically significant association with plaque progression.

Trial registration: NCT00799617.

Keywords: coronary artery disease; noncalcified coronary artery plaque; testosterone replacement.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anthropometry
  • Biomarkers / blood
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / chemically induced*
  • Coronary Artery Disease / diagnosis*
  • Disease Progression
  • Heart Disease Risk Factors
  • Hormone Replacement Therapy / adverse effects*
  • Humans
  • Hypogonadism / complications
  • Hypogonadism / drug therapy*
  • Male
  • Plaque, Atherosclerotic / blood
  • Plaque, Atherosclerotic / chemically induced
  • Plaque, Atherosclerotic / diagnosis
  • Testosterone / adverse effects*
  • Testosterone / therapeutic use


  • Biomarkers
  • Testosterone

Associated data