The effect of testosterone on cardiovascular biomarkers in the testosterone trials

Emile R. Mohler, Susan S. Ellenberg, Cora E. Lewis, Nanette K. Wenger, Matthew J. Budoff, Michael R. Lewis, Elizabeth Barrett-Connor, Ronald S. Swerdloff, Alisa Stephens-Shields, Shalender Bhasin, Jane A. Cauley, Jill P. Crandall, Glenn R. Cunningham, Kristine E. Ensrud, Thomas M. Gill, Alvin M. Matsumoto, Mark E. Molitch, Marco Pahor, Peter E. Preston, Xiaoling HouDenise Cifelli, Peter J. Snyder

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Context: Studies of the possible cardiovascular risk of testosterone treatment are inconclusive. Objective: To determine the effect of testosterone treatment on cardiovascular biomarkers in older men with low testosterone. Design: Double-blind, placebo-controlled trial. Setting: Twelve academic medical centers in the United States. Participants: In all, 788 men > 65 years old with an average of two serum testosterone levels ,275 ng/dL who were enrolled in The Testosterone Trials. Intervention: Testosterone gel, the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. Main Outcome Measures: Serum markers of cardiovascular risk, including lipids and markers of glucose metabolism, fibrinolysis, inflammation, and myocardial damage. Results: Compared with placebo, testosterone treatment significantly decreased total cholesterol (adjustedmean difference,26.1mg/dL; P < 0.001), high-density lipoprotein cholesterol (adjusted mean difference, 22.0mg/dL; P < 0.001), and low-density lipoprotein cholesterol (adjustedmean difference, 22.3 mg/dL; P = 0.051) from baseline to month 12. Testosterone also slightly but significantly decreased fasting insulin (adjusted mean difference, 21.7 mIU/mL; P = 0.02) and homeostatic model assessment insulin resistance (adjusted mean difference, 20.6; P = 0.03). Testosterone did not change triglycerides, D-dimer, C-reactive protein, interleukin 6, troponin, glucose, or hemoglobin A1c levels more than placebo. Conclusions and Relevance: Testosterone treatment of 1 year in oldermen with lowtestosteronewas associated withsmall reductions in cholesterol and insulin but not with other glucosemarkers,markers of inflammation or fibrinolysis, or troponin. The clinical importance of these findings is unclear and requires a larger trial of clinical outcomes.

Original languageEnglish (US)
Pages (from-to)681-688
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume103
Issue number2
DOIs
StatePublished - Feb 1 2018

Fingerprint

Biomarkers
Testosterone
Placebos
Troponin
Fibrinolysis
Insulin
Gels
Cholesterol
Inflammation
Glucose
Dilatation and Curettage
Therapeutics
LDL Cholesterol
HDL Cholesterol
Metabolism
Insulin Resistance
C-Reactive Protein
Interleukin-6
Fasting
Reference Values

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Mohler, E. R., Ellenberg, S. S., Lewis, C. E., Wenger, N. K., Budoff, M. J., Lewis, M. R., ... Snyder, P. J. (2018). The effect of testosterone on cardiovascular biomarkers in the testosterone trials. Journal of Clinical Endocrinology and Metabolism, 103(2), 681-688. https://doi.org/10.1210/jc.2017-02243

The effect of testosterone on cardiovascular biomarkers in the testosterone trials. / Mohler, Emile R.; Ellenberg, Susan S.; Lewis, Cora E.; Wenger, Nanette K.; Budoff, Matthew J.; Lewis, Michael R.; Barrett-Connor, Elizabeth; Swerdloff, Ronald S.; Stephens-Shields, Alisa; Bhasin, Shalender; Cauley, Jane A.; Crandall, Jill P.; Cunningham, Glenn R.; Ensrud, Kristine E.; Gill, Thomas M.; Matsumoto, Alvin M.; Molitch, Mark E.; Pahor, Marco; Preston, Peter E.; Hou, Xiaoling; Cifelli, Denise; Snyder, Peter J.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 103, No. 2, 01.02.2018, p. 681-688.

Research output: Contribution to journalArticle

Mohler, ER, Ellenberg, SS, Lewis, CE, Wenger, NK, Budoff, MJ, Lewis, MR, Barrett-Connor, E, Swerdloff, RS, Stephens-Shields, A, Bhasin, S, Cauley, JA, Crandall, JP, Cunningham, GR, Ensrud, KE, Gill, TM, Matsumoto, AM, Molitch, ME, Pahor, M, Preston, PE, Hou, X, Cifelli, D & Snyder, PJ 2018, 'The effect of testosterone on cardiovascular biomarkers in the testosterone trials', Journal of Clinical Endocrinology and Metabolism, vol. 103, no. 2, pp. 681-688. https://doi.org/10.1210/jc.2017-02243
Mohler, Emile R. ; Ellenberg, Susan S. ; Lewis, Cora E. ; Wenger, Nanette K. ; Budoff, Matthew J. ; Lewis, Michael R. ; Barrett-Connor, Elizabeth ; Swerdloff, Ronald S. ; Stephens-Shields, Alisa ; Bhasin, Shalender ; Cauley, Jane A. ; Crandall, Jill P. ; Cunningham, Glenn R. ; Ensrud, Kristine E. ; Gill, Thomas M. ; Matsumoto, Alvin M. ; Molitch, Mark E. ; Pahor, Marco ; Preston, Peter E. ; Hou, Xiaoling ; Cifelli, Denise ; Snyder, Peter J. / The effect of testosterone on cardiovascular biomarkers in the testosterone trials. In: Journal of Clinical Endocrinology and Metabolism. 2018 ; Vol. 103, No. 2. pp. 681-688.
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abstract = "Context: Studies of the possible cardiovascular risk of testosterone treatment are inconclusive. Objective: To determine the effect of testosterone treatment on cardiovascular biomarkers in older men with low testosterone. Design: Double-blind, placebo-controlled trial. Setting: Twelve academic medical centers in the United States. Participants: In all, 788 men > 65 years old with an average of two serum testosterone levels ,275 ng/dL who were enrolled in The Testosterone Trials. Intervention: Testosterone gel, the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. Main Outcome Measures: Serum markers of cardiovascular risk, including lipids and markers of glucose metabolism, fibrinolysis, inflammation, and myocardial damage. Results: Compared with placebo, testosterone treatment significantly decreased total cholesterol (adjustedmean difference,26.1mg/dL; P < 0.001), high-density lipoprotein cholesterol (adjusted mean difference, 22.0mg/dL; P < 0.001), and low-density lipoprotein cholesterol (adjustedmean difference, 22.3 mg/dL; P = 0.051) from baseline to month 12. Testosterone also slightly but significantly decreased fasting insulin (adjusted mean difference, 21.7 mIU/mL; P = 0.02) and homeostatic model assessment insulin resistance (adjusted mean difference, 20.6; P = 0.03). Testosterone did not change triglycerides, D-dimer, C-reactive protein, interleukin 6, troponin, glucose, or hemoglobin A1c levels more than placebo. Conclusions and Relevance: Testosterone treatment of 1 year in oldermen with lowtestosteronewas associated withsmall reductions in cholesterol and insulin but not with other glucosemarkers,markers of inflammation or fibrinolysis, or troponin. The clinical importance of these findings is unclear and requires a larger trial of clinical outcomes.",
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T1 - The effect of testosterone on cardiovascular biomarkers in the testosterone trials

AU - Mohler, Emile R.

AU - Ellenberg, Susan S.

AU - Lewis, Cora E.

AU - Wenger, Nanette K.

AU - Budoff, Matthew J.

AU - Lewis, Michael R.

AU - Barrett-Connor, Elizabeth

AU - Swerdloff, Ronald S.

AU - Stephens-Shields, Alisa

AU - Bhasin, Shalender

AU - Cauley, Jane A.

AU - Crandall, Jill P.

AU - Cunningham, Glenn R.

AU - Ensrud, Kristine E.

AU - Gill, Thomas M.

AU - Matsumoto, Alvin M.

AU - Molitch, Mark E.

AU - Pahor, Marco

AU - Preston, Peter E.

AU - Hou, Xiaoling

AU - Cifelli, Denise

AU - Snyder, Peter J.

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N2 - Context: Studies of the possible cardiovascular risk of testosterone treatment are inconclusive. Objective: To determine the effect of testosterone treatment on cardiovascular biomarkers in older men with low testosterone. Design: Double-blind, placebo-controlled trial. Setting: Twelve academic medical centers in the United States. Participants: In all, 788 men > 65 years old with an average of two serum testosterone levels ,275 ng/dL who were enrolled in The Testosterone Trials. Intervention: Testosterone gel, the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. Main Outcome Measures: Serum markers of cardiovascular risk, including lipids and markers of glucose metabolism, fibrinolysis, inflammation, and myocardial damage. Results: Compared with placebo, testosterone treatment significantly decreased total cholesterol (adjustedmean difference,26.1mg/dL; P < 0.001), high-density lipoprotein cholesterol (adjusted mean difference, 22.0mg/dL; P < 0.001), and low-density lipoprotein cholesterol (adjustedmean difference, 22.3 mg/dL; P = 0.051) from baseline to month 12. Testosterone also slightly but significantly decreased fasting insulin (adjusted mean difference, 21.7 mIU/mL; P = 0.02) and homeostatic model assessment insulin resistance (adjusted mean difference, 20.6; P = 0.03). Testosterone did not change triglycerides, D-dimer, C-reactive protein, interleukin 6, troponin, glucose, or hemoglobin A1c levels more than placebo. Conclusions and Relevance: Testosterone treatment of 1 year in oldermen with lowtestosteronewas associated withsmall reductions in cholesterol and insulin but not with other glucosemarkers,markers of inflammation or fibrinolysis, or troponin. The clinical importance of these findings is unclear and requires a larger trial of clinical outcomes.

AB - Context: Studies of the possible cardiovascular risk of testosterone treatment are inconclusive. Objective: To determine the effect of testosterone treatment on cardiovascular biomarkers in older men with low testosterone. Design: Double-blind, placebo-controlled trial. Setting: Twelve academic medical centers in the United States. Participants: In all, 788 men > 65 years old with an average of two serum testosterone levels ,275 ng/dL who were enrolled in The Testosterone Trials. Intervention: Testosterone gel, the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. Main Outcome Measures: Serum markers of cardiovascular risk, including lipids and markers of glucose metabolism, fibrinolysis, inflammation, and myocardial damage. Results: Compared with placebo, testosterone treatment significantly decreased total cholesterol (adjustedmean difference,26.1mg/dL; P < 0.001), high-density lipoprotein cholesterol (adjusted mean difference, 22.0mg/dL; P < 0.001), and low-density lipoprotein cholesterol (adjustedmean difference, 22.3 mg/dL; P = 0.051) from baseline to month 12. Testosterone also slightly but significantly decreased fasting insulin (adjusted mean difference, 21.7 mIU/mL; P = 0.02) and homeostatic model assessment insulin resistance (adjusted mean difference, 20.6; P = 0.03). Testosterone did not change triglycerides, D-dimer, C-reactive protein, interleukin 6, troponin, glucose, or hemoglobin A1c levels more than placebo. Conclusions and Relevance: Testosterone treatment of 1 year in oldermen with lowtestosteronewas associated withsmall reductions in cholesterol and insulin but not with other glucosemarkers,markers of inflammation or fibrinolysis, or troponin. The clinical importance of these findings is unclear and requires a larger trial of clinical outcomes.

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