title: Association of Testosterone Levels With Anemia in Older Men: A Controlled Clinical Trial.
abstract: In one-third of older men with anemia, no recognized cause can be found.
  
  
  
  To determine if testosterone treatment of men 65 years or older with unequivocally low testosterone levels and unexplained anemia would increase their hemoglobin concentration.
  
  
  
  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.
  
  
  
  Testosterone gel, the dose adjusted to maintain the testosterone levels normal for young men, or placebo gel for 12 months.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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 increases may 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.
  
  
  
  clinicaltrials.gov Identifier: NCT00799617.
authors.affiliation: Divisions of Geriatric Medicine and Gerontology and Hematology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Cindy N
authors.initials: CN
authors.lastname: Roy
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Snyder
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Alisa J
authors.initials: AJ
authors.lastname: Stephens-Shields
authors.affiliation: Section of Hematology/Oncology, University of Chicago, Chicago, Illinois.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Artz
authors.affiliation: Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
authors.affiliation: Duke University Medical Center, Center for the Study of Aging, Durham, North Carolina.
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Cohen
authors.affiliation: Center for Clinical Epidemiology & Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: John T
authors.initials: JT
authors.lastname: Farrar
authors.affiliation: Division of Geriatric Medicine, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Gill
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Bret
authors.initials: B
authors.lastname: Zeldow
authors.affiliation: Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: David
authors.initials: D
authors.lastname: Cella
authors.affiliation: Department of Internal Medicine and Division of Epidemiology, Department of Family Medicine and Public Health, University of California, San Diego School of Medicine, La Jolla.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Barrett-Connor
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, Pennsylvania.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.affiliation: Divisions of Endocrinology and Geriatrics, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Jill P
authors.initials: JP
authors.lastname: Crandall
authors.affiliation: Departments of Medicine and Molecular & Cellular Biology, Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine and Baylor St Luke's Medical Center, Houston, Texas.
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Cunningham
authors.affiliation: Department of Medicine, Division of Epidemiology & Community Health, University of Minnesota, Minneapolis.|Minneapolis VA Health Care System, Minneapolis, Minnesota.
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Ensrud
authors.affiliation: Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham.
authors.forename: Cora E
authors.initials: CE
authors.lastname: Lewis
authors.affiliation: Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Puget Sound Health Care System, and Division of Gerontology & Geriatric Medicine, Department of Internal Medicine, University of Washington School of Medicine, Seattle.
authors.forename: Alvin M
authors.initials: AM
authors.lastname: Matsumoto
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Molitch
authors.affiliation: Department of Aging & Geriatric Research, University of Florida, Gainesville, Florida.
authors.forename: Marco
authors.initials: M
authors.lastname: Pahor
authors.affiliation: Division of Endocrinology, Harbor-University of California at Los Angeles Medical Center and Los Angeles Biomedical Research Institute; Torrance.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Swerdloff
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Denise
authors.initials: D
authors.lastname: Cifelli
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Hou
authors.affiliation: Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
authors.affiliation: Division of Geriatric Medicine and Gerontology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Walston
authors.affiliation: Department of Aging & Geriatric Research, University of Florida, Gainesville, Florida.
authors.forename: Stephen
authors.initials: S
authors.lastname: Anton
authors.affiliation: Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Shehzad
authors.initials: S
authors.lastname: Basaria
authors.affiliation: Department of Medicine, Division of Epidemiology & Community Health, University of Minnesota, Minneapolis.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Diem
authors.affiliation: Division of Endocrinology, Harbor-University of California at Los Angeles Medical Center and Los Angeles Biomedical Research Institute; Torrance.
authors.forename: Christina
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Medicine, Stanford University, Stanford, California.
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Schrier
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Ellenberg
mesh_terms: D000368:Aged; D000728:Androgens / Q000008:administration & dosage / Q000097:blood / Q000172:deficiency; D000740:Anemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy; D004311:Double-Blind Method; D004333:Drug Administration Routes; D016903:Drug Monitoring / Q000379:methods; D006454:Hemoglobins / Q000032:analysis*; D020249:Hormone Replacement Therapy / Q000379:methods; D006801:Humans; D008297:Male; D013739:Testosterone / Q000008:administration & dosage / Q000097:blood / Q000172:deficiency; D016896:Treatment Outcome
chemical_list: D000728:Androgens; D006454:Hemoglobins; D013739:Testosterone