Association of testosterone levels with anemia in older men a controlled clinical trial

Cindy N. Roy, Peter J. Snyder, Alisa J. Stephens-Shields, Andrew S. Artz, Shalender Bhasin, Harvey J. Cohen, John T. Farrar, Thomas M. Gill, Bret Zeldow, David Cella, Elizabeth Barrett-Connor, Jane A. Cauley, Jill P. Crandall, Glenn R. Cunningham, Kristine E. Ensrud, Cora E. Lewis, Alvin M. Matsumoto, Mark E. Molitch, Marco Pahor, Ronald S. Swerdloff & 10 others Denise Cifelli, Xiaoling Hou, Susan Resnick, Jeremy D. Walston, Stephen Anton, Shehzad Basaria, Susan J. Diem, Christina Wang, Stanley L. Schrier, Susan S. Ellenberg

Research output: Contribution to journalArticle

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Abstract

IMPORTANCE In one-third of older men with anemia, no recognized cause can be found. OBJECTIVE To determine if testosterone treatment of men 65 years or older with unequivocally low testosterone levels and unexplained anemia would increase their hemoglobin concentration. DESIGN, SETTING, AND PARTICIPANTS A double-blinded, placebo-controlled trial with treatment allocation by minimization using 788 men 65 years or older who have average testosterone levels of less than 275 ng/dL. Of 788 participants, 126 were anemic (hemoglobin ≥12.7 g/dL), 62 of whom had no known cause. The trial was conducted in 12 academic medical centers in the United States from June 2010 to June 2014. INTERVENTIONS Testosterone gel, the dose adjusted to maintain the testosterone levels normal for young men, or placebo gel for 12 months. MAIN OUTCOMES AND MEASURES The percent of men with unexplained anemia whose hemoglobin levels increased by 1.0 g/dL or more in response to testosterone compared with placebo. The statistical analysis was intent-to-treat by a logistic mixed effects model adjusted for balancing factors. RESULTS The men had a mean age of 74.8 years and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 30.7; 84.9% were white. Testosterone treatment resulted in a greater percentage of men with unexplained anemia whose month 12 hemoglobin levels had increased by 1.0 g/dL or more over baseline (54%) than did placebo (15%) (adjusted OR, 31.5; 95%CI, 3.7-277.8; P = .002) and a greater percentage of men who at month 12 were no longer anemic (58.3%) compared with placebo (22.2%) (adjusted OR, 17.0; 95%CI, 2.8-104.0; P = .002). Testosterone treatment also resulted in a greater percentage of men with anemia of known cause whose month 12 hemoglobin levels had increased by 1.0 g/dL or more (52%) than did placebo (19%) (adjusted OR, 8.2; 95%CI, 2.1-31.9; P = .003). Testosterone treatment resulted in a hemoglobin concentration of more than 17.5 g/dL in 6 men who had not been anemic at baseline. CONCLUSIONS AND RELEVANCE Among older men with low testosterone levels, testosterone treatment significantly increased the hemoglobin levels of those with unexplained anemia as well as those with anemia from known causes. These increasesmay be of clinical value, as suggested by the magnitude of the changes and the correction of anemia in most men, but the overall health benefits remain to be established. Measurement of testosterone levels might be considered in men 65 years or older who have unexplained anemia and symptoms of low testosterone levels.

Original languageEnglish (US)
Pages (from-to)480-490
Number of pages11
JournalJAMA Internal Medicine
Volume177
Issue number4
DOIs
StatePublished - Apr 1 2017

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Controlled Clinical Trials
Testosterone
Anemia
Hemoglobins
Placebos
Therapeutics
Gels
Men's Health
Insurance Benefits
Body Mass Index

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Roy, C. N., Snyder, P. J., Stephens-Shields, A. J., Artz, A. S., Bhasin, S., Cohen, H. J., ... Ellenberg, S. S. (2017). Association of testosterone levels with anemia in older men a controlled clinical trial. JAMA Internal Medicine, 177(4), 480-490. https://doi.org/10.1001/jamainternmed.2016.9540

Association of testosterone levels with anemia in older men a controlled clinical trial. / Roy, Cindy N.; Snyder, Peter J.; Stephens-Shields, Alisa J.; Artz, Andrew S.; Bhasin, Shalender; Cohen, Harvey J.; Farrar, John T.; Gill, Thomas M.; Zeldow, Bret; Cella, David; Barrett-Connor, Elizabeth; Cauley, Jane A.; Crandall, Jill P.; Cunningham, Glenn R.; Ensrud, Kristine E.; Lewis, Cora E.; Matsumoto, Alvin M.; Molitch, Mark E.; Pahor, Marco; Swerdloff, Ronald S.; Cifelli, Denise; Hou, Xiaoling; Resnick, Susan; Walston, Jeremy D.; Anton, Stephen; Basaria, Shehzad; Diem, Susan J.; Wang, Christina; Schrier, Stanley L.; Ellenberg, Susan S.

In: JAMA Internal Medicine, Vol. 177, No. 4, 01.04.2017, p. 480-490.

Research output: Contribution to journalArticle

Roy, CN, Snyder, PJ, Stephens-Shields, AJ, Artz, AS, Bhasin, S, Cohen, HJ, Farrar, JT, Gill, TM, Zeldow, B, Cella, D, Barrett-Connor, E, Cauley, JA, Crandall, JP, Cunningham, GR, Ensrud, KE, Lewis, CE, Matsumoto, AM, Molitch, ME, Pahor, M, Swerdloff, RS, Cifelli, D, Hou, X, Resnick, S, Walston, JD, Anton, S, Basaria, S, Diem, SJ, Wang, C, Schrier, SL & Ellenberg, SS 2017, 'Association of testosterone levels with anemia in older men a controlled clinical trial', JAMA Internal Medicine, vol. 177, no. 4, pp. 480-490. https://doi.org/10.1001/jamainternmed.2016.9540
Roy CN, Snyder PJ, Stephens-Shields AJ, Artz AS, Bhasin S, Cohen HJ et al. Association of testosterone levels with anemia in older men a controlled clinical trial. JAMA Internal Medicine. 2017 Apr 1;177(4):480-490. https://doi.org/10.1001/jamainternmed.2016.9540
Roy, Cindy N. ; Snyder, Peter J. ; Stephens-Shields, Alisa J. ; Artz, Andrew S. ; Bhasin, Shalender ; Cohen, Harvey J. ; Farrar, John T. ; Gill, Thomas M. ; Zeldow, Bret ; Cella, David ; Barrett-Connor, Elizabeth ; Cauley, Jane A. ; Crandall, Jill P. ; Cunningham, Glenn R. ; Ensrud, Kristine E. ; Lewis, Cora E. ; Matsumoto, Alvin M. ; Molitch, Mark E. ; Pahor, Marco ; Swerdloff, Ronald S. ; Cifelli, Denise ; Hou, Xiaoling ; Resnick, Susan ; Walston, Jeremy D. ; Anton, Stephen ; Basaria, Shehzad ; Diem, Susan J. ; Wang, Christina ; Schrier, Stanley L. ; Ellenberg, Susan S. / Association of testosterone levels with anemia in older men a controlled clinical trial. In: JAMA Internal Medicine. 2017 ; Vol. 177, No. 4. pp. 480-490.
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abstract = "IMPORTANCE In one-third of older men with anemia, no recognized cause can be found. OBJECTIVE To determine if testosterone treatment of men 65 years or older with unequivocally low testosterone levels and unexplained anemia would increase their hemoglobin concentration. DESIGN, SETTING, AND PARTICIPANTS A double-blinded, placebo-controlled trial with treatment allocation by minimization using 788 men 65 years or older who have average testosterone levels of less than 275 ng/dL. Of 788 participants, 126 were anemic (hemoglobin ≥12.7 g/dL), 62 of whom had no known cause. The trial was conducted in 12 academic medical centers in the United States from June 2010 to June 2014. INTERVENTIONS Testosterone gel, the dose adjusted to maintain the testosterone levels normal for young men, or placebo gel for 12 months. MAIN OUTCOMES AND MEASURES The percent of men with unexplained anemia whose hemoglobin levels increased by 1.0 g/dL or more in response to testosterone compared with placebo. The statistical analysis was intent-to-treat by a logistic mixed effects model adjusted for balancing factors. RESULTS The men had a mean age of 74.8 years and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 30.7; 84.9{\%} were white. Testosterone treatment resulted in a greater percentage of men with unexplained anemia whose month 12 hemoglobin levels had increased by 1.0 g/dL or more over baseline (54{\%}) than did placebo (15{\%}) (adjusted OR, 31.5; 95{\%}CI, 3.7-277.8; P = .002) and a greater percentage of men who at month 12 were no longer anemic (58.3{\%}) compared with placebo (22.2{\%}) (adjusted OR, 17.0; 95{\%}CI, 2.8-104.0; P = .002). Testosterone treatment also resulted in a greater percentage of men with anemia of known cause whose month 12 hemoglobin levels had increased by 1.0 g/dL or more (52{\%}) than did placebo (19{\%}) (adjusted OR, 8.2; 95{\%}CI, 2.1-31.9; P = .003). Testosterone treatment resulted in a hemoglobin concentration of more than 17.5 g/dL in 6 men who had not been anemic at baseline. CONCLUSIONS AND RELEVANCE Among older men with low testosterone levels, testosterone treatment significantly increased the hemoglobin levels of those with unexplained anemia as well as those with anemia from known causes. These increasesmay be of clinical value, as suggested by the magnitude of the changes and the correction of anemia in most men, but the overall health benefits remain to be established. Measurement of testosterone levels might be considered in men 65 years or older who have unexplained anemia and symptoms of low testosterone levels.",
author = "Roy, {Cindy N.} and Snyder, {Peter J.} and Stephens-Shields, {Alisa J.} and Artz, {Andrew S.} and Shalender Bhasin and Cohen, {Harvey J.} and Farrar, {John T.} and Gill, {Thomas M.} and Bret Zeldow and David Cella and Elizabeth Barrett-Connor and Cauley, {Jane A.} and Crandall, {Jill P.} and Cunningham, {Glenn R.} and Ensrud, {Kristine E.} and Lewis, {Cora E.} and Matsumoto, {Alvin M.} and Molitch, {Mark E.} and Marco Pahor and Swerdloff, {Ronald S.} and Denise Cifelli and Xiaoling Hou and Susan Resnick and Walston, {Jeremy D.} and Stephen Anton and Shehzad Basaria and Diem, {Susan J.} and Christina Wang and Schrier, {Stanley L.} and Ellenberg, {Susan S.}",
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TY - JOUR

T1 - Association of testosterone levels with anemia in older men a controlled clinical trial

AU - Roy, Cindy N.

AU - Snyder, Peter J.

AU - Stephens-Shields, Alisa J.

AU - Artz, Andrew S.

AU - Bhasin, Shalender

AU - Cohen, Harvey J.

AU - Farrar, John T.

AU - Gill, Thomas M.

AU - Zeldow, Bret

AU - Cella, David

AU - Barrett-Connor, Elizabeth

AU - Cauley, Jane A.

AU - Crandall, Jill P.

AU - Cunningham, Glenn R.

AU - Ensrud, Kristine E.

AU - Lewis, Cora E.

AU - Matsumoto, Alvin M.

AU - Molitch, Mark E.

AU - Pahor, Marco

AU - Swerdloff, Ronald S.

AU - Cifelli, Denise

AU - Hou, Xiaoling

AU - Resnick, Susan

AU - Walston, Jeremy D.

AU - Anton, Stephen

AU - Basaria, Shehzad

AU - Diem, Susan J.

AU - Wang, Christina

AU - Schrier, Stanley L.

AU - Ellenberg, Susan S.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - IMPORTANCE In one-third of older men with anemia, no recognized cause can be found. OBJECTIVE To determine if testosterone treatment of men 65 years or older with unequivocally low testosterone levels and unexplained anemia would increase their hemoglobin concentration. DESIGN, SETTING, AND PARTICIPANTS A double-blinded, placebo-controlled trial with treatment allocation by minimization using 788 men 65 years or older who have average testosterone levels of less than 275 ng/dL. Of 788 participants, 126 were anemic (hemoglobin ≥12.7 g/dL), 62 of whom had no known cause. The trial was conducted in 12 academic medical centers in the United States from June 2010 to June 2014. INTERVENTIONS Testosterone gel, the dose adjusted to maintain the testosterone levels normal for young men, or placebo gel for 12 months. MAIN OUTCOMES AND MEASURES The percent of men with unexplained anemia whose hemoglobin levels increased by 1.0 g/dL or more in response to testosterone compared with placebo. The statistical analysis was intent-to-treat by a logistic mixed effects model adjusted for balancing factors. RESULTS The men had a mean age of 74.8 years and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 30.7; 84.9% were white. Testosterone treatment resulted in a greater percentage of men with unexplained anemia whose month 12 hemoglobin levels had increased by 1.0 g/dL or more over baseline (54%) than did placebo (15%) (adjusted OR, 31.5; 95%CI, 3.7-277.8; P = .002) and a greater percentage of men who at month 12 were no longer anemic (58.3%) compared with placebo (22.2%) (adjusted OR, 17.0; 95%CI, 2.8-104.0; P = .002). Testosterone treatment also resulted in a greater percentage of men with anemia of known cause whose month 12 hemoglobin levels had increased by 1.0 g/dL or more (52%) than did placebo (19%) (adjusted OR, 8.2; 95%CI, 2.1-31.9; P = .003). Testosterone treatment resulted in a hemoglobin concentration of more than 17.5 g/dL in 6 men who had not been anemic at baseline. CONCLUSIONS AND RELEVANCE Among older men with low testosterone levels, testosterone treatment significantly increased the hemoglobin levels of those with unexplained anemia as well as those with anemia from known causes. These increasesmay be of clinical value, as suggested by the magnitude of the changes and the correction of anemia in most men, but the overall health benefits remain to be established. Measurement of testosterone levels might be considered in men 65 years or older who have unexplained anemia and symptoms of low testosterone levels.

AB - IMPORTANCE In one-third of older men with anemia, no recognized cause can be found. OBJECTIVE To determine if testosterone treatment of men 65 years or older with unequivocally low testosterone levels and unexplained anemia would increase their hemoglobin concentration. DESIGN, SETTING, AND PARTICIPANTS A double-blinded, placebo-controlled trial with treatment allocation by minimization using 788 men 65 years or older who have average testosterone levels of less than 275 ng/dL. Of 788 participants, 126 were anemic (hemoglobin ≥12.7 g/dL), 62 of whom had no known cause. The trial was conducted in 12 academic medical centers in the United States from June 2010 to June 2014. INTERVENTIONS Testosterone gel, the dose adjusted to maintain the testosterone levels normal for young men, or placebo gel for 12 months. MAIN OUTCOMES AND MEASURES The percent of men with unexplained anemia whose hemoglobin levels increased by 1.0 g/dL or more in response to testosterone compared with placebo. The statistical analysis was intent-to-treat by a logistic mixed effects model adjusted for balancing factors. RESULTS The men had a mean age of 74.8 years and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 30.7; 84.9% were white. Testosterone treatment resulted in a greater percentage of men with unexplained anemia whose month 12 hemoglobin levels had increased by 1.0 g/dL or more over baseline (54%) than did placebo (15%) (adjusted OR, 31.5; 95%CI, 3.7-277.8; P = .002) and a greater percentage of men who at month 12 were no longer anemic (58.3%) compared with placebo (22.2%) (adjusted OR, 17.0; 95%CI, 2.8-104.0; P = .002). Testosterone treatment also resulted in a greater percentage of men with anemia of known cause whose month 12 hemoglobin levels had increased by 1.0 g/dL or more (52%) than did placebo (19%) (adjusted OR, 8.2; 95%CI, 2.1-31.9; P = .003). Testosterone treatment resulted in a hemoglobin concentration of more than 17.5 g/dL in 6 men who had not been anemic at baseline. CONCLUSIONS AND RELEVANCE Among older men with low testosterone levels, testosterone treatment significantly increased the hemoglobin levels of those with unexplained anemia as well as those with anemia from known causes. These increasesmay be of clinical value, as suggested by the magnitude of the changes and the correction of anemia in most men, but the overall health benefits remain to be established. Measurement of testosterone levels might be considered in men 65 years or older who have unexplained anemia and symptoms of low testosterone levels.

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