title: Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone.
abstract: Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk.
  
  
  
  To test the hypothesis that testosterone treatment of older men with low testosterone slows progression of noncalcified coronary artery plaque volume.
  
  
  
  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.
  
  
  
  Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months.
  
  
  
  The primary outcome was 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  clinicaltrials.gov Identifier: NCT00799617.
authors.affiliation: Division of Cardiology, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Budoff
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
authors.affiliation: Division of Preventive Medicine, University of Alabama at Birmingham.
authors.forename: Cora E
authors.initials: CE
authors.lastname: Lewis
authors.affiliation: Section of Vascular Medicine, Division of Cardiovascular Disease, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Emile R
authors.initials: ER
authors.lastname: Mohler
authors.affiliation: Division of Cardiology, Department of Medicine, Emory Heart and Vascular Center, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Nanette K
authors.initials: NK
authors.lastname: Wenger
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: Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego School of Medicine, La Jolla.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Barrett-Connor
authors.affiliation: Division of Endocrinology, Los Angeles Biomedical Research Institute, Harbor-UCLA, Torrance, California.
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: Alisa
authors.initials: A
authors.lastname: Stephens-Shields
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.affiliation: Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York11Division of Geriatrics, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Jill P
authors.initials: JP
authors.lastname: Crandall
authors.affiliation: Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine and Baylor St. Luke's Medical Center, Houston, Texas13Department of Molecular and Cell Biology, 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: Division of Epidemiology and Community Health, Department of Medicine, University of Minnesota, Minneapolis15Minneapolis VA Health Care System, Minneapolis, Minnesota.
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Ensrud
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: Geriatric Research, Education, and Clinical Center, VA Puget Sound Health System, University of Washington School of Medicine, Seattle18Division of Gerontology and 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: Division of Cardiology, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Rine
authors.initials: R
authors.lastname: Nakanishi
authors.affiliation: Division of Cardiology, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Negin
authors.initials: N
authors.lastname: Nezarat
authors.affiliation: Division of Cardiology, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Suguru
authors.initials: S
authors.lastname: Matsumoto
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: 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: Division of Epidemiology and Community Health, Department of Medicine, University of Minnesota, Minneapolis.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Diem
authors.affiliation: Division of Endocrinology, Los Angeles Biomedical Research Institute, Harbor-UCLA, Torrance, California.
authors.forename: Christina
authors.initials: C
authors.lastname: Wang
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: Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Snyder
mesh_terms: D000368:Aged; D000728:Androgens / Q000008:administration & dosage / Q000009:adverse effects*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000139:chemically induced* / Q000000981:diagnostic imaging*; D018450:Disease Progression; D004311:Double-Blind Method; D005782:Gels; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000188:drug therapy; D008297:Male; D015588:Observer Variation; D018401:Sample Size; D013739:Testosterone / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D014481:United States; D061205:Vascular Calcification / Q000000981:diagnostic imaging*
chemical_list: D000728:Androgens; D005782:Gels; D013739:Testosterone