Testosterone treatment and coronary artery plaque volume in older men with low testosterone

Matthew J. Budoff, Susan S. Ellenberg, Cora E. Lewis, Emile R. Mohler, Nanette K. Wenger, Shalender Bhasin, Elizabeth Barrett-Connor, Ronald S. Swerdloff, Alisa Stephens-Shields, Jane A. Cauley, Jill P. Crandall, Glenn R. Cunningham, Kristine E. Ensrud, Thomas M. Gill, Alvin M. Matsumoto, Mark E. Molitch, Rine Nakanishi, Negin Nezarat, Suguru Matsumoto, Xiaoling HouShehzad Basaria, Susan J. Diem, Christina Wang, Denise Cifelli, Peter J. Snyder

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Importance: Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk. Objective: To test the hypothesis that testosterone treatment of older men with low testosterone slows progression of noncalcified coronary artery plaque volume. Design, Setting, and Participants: Double-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014. Intervention: Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. Main Outcomes and Measures: The primary outcomewas noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis). Results: Of 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81%were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95%CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm3 to 318 mm3 in the testosterone group vs from 499 mm3 to 541 mm3 in the placebo group (estimated difference, 47 mm3; 95%CI, 13 to 80 mm3; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 503 Agatston units in the placebo group (estimated difference, -27 Agatston units; 95%CI, -80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group. Conclusions and Relevance: Among older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding.

Original languageEnglish (US)
Pages (from-to)708-716
Number of pages9
JournalJAMA - Journal of the American Medical Association
Volume317
Issue number7
DOIs
StatePublished - Feb 21 2017

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Testosterone
Coronary Vessels
Placebos
Therapeutics
Hypogonadism
Gels
Atherosclerosis
Angiography
Reference Values
Outcome Assessment (Health Care)
Calcium

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Budoff, M. J., Ellenberg, S. S., Lewis, C. E., Mohler, E. R., Wenger, N. K., Bhasin, S., ... Snyder, P. J. (2017). Testosterone treatment and coronary artery plaque volume in older men with low testosterone. JAMA - Journal of the American Medical Association, 317(7), 708-716. https://doi.org/10.1001/jama.2016.21043

Testosterone treatment and coronary artery plaque volume in older men with low testosterone. / Budoff, Matthew J.; Ellenberg, Susan S.; Lewis, Cora E.; Mohler, Emile R.; Wenger, Nanette K.; Bhasin, Shalender; Barrett-Connor, Elizabeth; Swerdloff, Ronald S.; Stephens-Shields, Alisa; Cauley, Jane A.; Crandall, Jill P.; Cunningham, Glenn R.; Ensrud, Kristine E.; Gill, Thomas M.; Matsumoto, Alvin M.; Molitch, Mark E.; Nakanishi, Rine; Nezarat, Negin; Matsumoto, Suguru; Hou, Xiaoling; Basaria, Shehzad; Diem, Susan J.; Wang, Christina; Cifelli, Denise; Snyder, Peter J.

In: JAMA - Journal of the American Medical Association, Vol. 317, No. 7, 21.02.2017, p. 708-716.

Research output: Contribution to journalArticle

Budoff, MJ, Ellenberg, SS, Lewis, CE, Mohler, ER, Wenger, NK, Bhasin, S, Barrett-Connor, E, Swerdloff, RS, Stephens-Shields, A, Cauley, JA, Crandall, JP, Cunningham, GR, Ensrud, KE, Gill, TM, Matsumoto, AM, Molitch, ME, Nakanishi, R, Nezarat, N, Matsumoto, S, Hou, X, Basaria, S, Diem, SJ, Wang, C, Cifelli, D & Snyder, PJ 2017, 'Testosterone treatment and coronary artery plaque volume in older men with low testosterone', JAMA - Journal of the American Medical Association, vol. 317, no. 7, pp. 708-716. https://doi.org/10.1001/jama.2016.21043
Budoff, Matthew J. ; Ellenberg, Susan S. ; Lewis, Cora E. ; Mohler, Emile R. ; Wenger, Nanette K. ; Bhasin, Shalender ; Barrett-Connor, Elizabeth ; Swerdloff, Ronald S. ; Stephens-Shields, Alisa ; Cauley, Jane A. ; Crandall, Jill P. ; Cunningham, Glenn R. ; Ensrud, Kristine E. ; Gill, Thomas M. ; Matsumoto, Alvin M. ; Molitch, Mark E. ; Nakanishi, Rine ; Nezarat, Negin ; Matsumoto, Suguru ; Hou, Xiaoling ; Basaria, Shehzad ; Diem, Susan J. ; Wang, Christina ; Cifelli, Denise ; Snyder, Peter J. / Testosterone treatment and coronary artery plaque volume in older men with low testosterone. In: JAMA - Journal of the American Medical Association. 2017 ; Vol. 317, No. 7. pp. 708-716.
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abstract = "Importance: Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk. Objective: To test the hypothesis that testosterone treatment of older men with low testosterone slows progression of noncalcified coronary artery plaque volume. Design, Setting, and Participants: Double-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014. Intervention: Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. Main Outcomes and Measures: The primary outcomewas noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis). Results: Of 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81{\%}were white. At baseline, 70 men (50.7{\%}) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95{\%}CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm3 to 318 mm3 in the testosterone group vs from 499 mm3 to 541 mm3 in the placebo group (estimated difference, 47 mm3; 95{\%}CI, 13 to 80 mm3; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 503 Agatston units in the placebo group (estimated difference, -27 Agatston units; 95{\%}CI, -80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group. Conclusions and Relevance: Among older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding.",
author = "Budoff, {Matthew J.} and Ellenberg, {Susan S.} and Lewis, {Cora E.} and Mohler, {Emile R.} and Wenger, {Nanette K.} and Shalender Bhasin and Elizabeth Barrett-Connor and Swerdloff, {Ronald S.} and Alisa Stephens-Shields and Cauley, {Jane A.} and Crandall, {Jill P.} and Cunningham, {Glenn R.} and Ensrud, {Kristine E.} and Gill, {Thomas M.} and Matsumoto, {Alvin M.} and Molitch, {Mark E.} and Rine Nakanishi and Negin Nezarat and Suguru Matsumoto and Xiaoling Hou and Shehzad Basaria and Diem, {Susan J.} and Christina Wang and Denise Cifelli and Snyder, {Peter J.}",
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TY - JOUR

T1 - Testosterone treatment and coronary artery plaque volume in older men with low testosterone

AU - Budoff, Matthew J.

AU - Ellenberg, Susan S.

AU - Lewis, Cora E.

AU - Mohler, Emile R.

AU - Wenger, Nanette K.

AU - Bhasin, Shalender

AU - Barrett-Connor, Elizabeth

AU - Swerdloff, Ronald S.

AU - Stephens-Shields, Alisa

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 - Nakanishi, Rine

AU - Nezarat, Negin

AU - Matsumoto, Suguru

AU - Hou, Xiaoling

AU - Basaria, Shehzad

AU - Diem, Susan J.

AU - Wang, Christina

AU - Cifelli, Denise

AU - Snyder, Peter J.

PY - 2017/2/21

Y1 - 2017/2/21

N2 - Importance: Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk. Objective: To test the hypothesis that testosterone treatment of older men with low testosterone slows progression of noncalcified coronary artery plaque volume. Design, Setting, and Participants: Double-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014. Intervention: Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. Main Outcomes and Measures: The primary outcomewas noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis). Results: Of 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81%were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95%CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm3 to 318 mm3 in the testosterone group vs from 499 mm3 to 541 mm3 in the placebo group (estimated difference, 47 mm3; 95%CI, 13 to 80 mm3; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 503 Agatston units in the placebo group (estimated difference, -27 Agatston units; 95%CI, -80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group. Conclusions and Relevance: Among older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding.

AB - Importance: Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk. Objective: To test the hypothesis that testosterone treatment of older men with low testosterone slows progression of noncalcified coronary artery plaque volume. Design, Setting, and Participants: Double-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014. Intervention: Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. Main Outcomes and Measures: The primary outcomewas noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis). Results: Of 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81%were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95%CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm3 to 318 mm3 in the testosterone group vs from 499 mm3 to 541 mm3 in the placebo group (estimated difference, 47 mm3; 95%CI, 13 to 80 mm3; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 503 Agatston units in the placebo group (estimated difference, -27 Agatston units; 95%CI, -80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group. Conclusions and Relevance: Among older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding.

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