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.
Bibliographical noteFunding Information:
The Testosterone Trials were supported by a grant from the National Institute on Aging, National Institutes of Health (U01 AG030644), supplemented by funds from the National Heart, Lung, and Blood Institute, National Institute of Neurological Diseases and Stroke, and National Institute of Child Health and Human Development. The Anemia Trial was additionally supported by a grant from the National Institute on Aging, National Institutes of Health (U01 AG034661) to the Partnership for Anemia Clinical and Translational Trials in the Elderly consortium. AbbVie (formerly Solvay and Abbott Laboratories) generously provided funding, AndroGel, and placebo gel. Dr Gill is the recipient of an Academic Leadership Award (K07AG043587) from the National Institute on Aging. The Yale Field Center was partially supported by the Claude D. Pepper Older Americans Independence Center (P30AG021342). Dr Bhasin and the Boston Center was supported partly by the Boston Claude D. Pepper Older Americans Independence Center grant 5P30AG031679. The University of Florida's Field Center was also partially supported by the Claude D. Pepper Older Americans Independence Center (NIH/NIA P30AG028740).
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