title: Risk factors associated with cardiovascular events during testosterone administration in older men with mobility limitation.
abstract: BACKGROUND
  Testosterone in Older Men with Mobility Limitations Trial found an increased incidence of cardiovascular events in men randomized to testosterone, resulting in enrollment cessation by trial's Data and Safety Monitoring Board. We evaluated changes in gonadal hormones and markers of inflammation and coagulation to elucidate risk factors associated with cardiovascular events.
  
  
  METHODS
  Men aged 65 years or more, with mobility limitation, total testosterone 100-350 ng/dL, or free testosterone less than 50 pg/mL, were randomized to placebo or 10 g testosterone gel daily for 6 months. Changes in total and free testosterone, estradiol and estrone, C-reactive protein, interleukin 6, fibrinogen, plasminogen activator inhibitor-1, and pro-brain naturetic peptide were compared between groups and within the testosterone group between subjects who experienced cardiovascular events and those who did not.
  
  
  RESULTS
  Of 209 men randomized (mean age 74 years), gonadal hormones and biomarkers were available in 179 men. Baseline body mass index, gonadal hormones, lipids, Framingham risk scores, and other biomarkers were similar in the two treatment groups. Within the testosterone group, the 6-month increase in free testosterone was significantly greater in men who experienced cardiovascular events than in those who did not [mean (95% confidence interval), 10.6 (4.6-16.7) vs 5.2 (3.0-7.5) ng/dL, p = .05]. In multivariable logistic regression analysis, the change in the serum levels of free testosterone was associated with cardiovascular events.
  
  
  CONCLUSIONS
  Mobility-limited older men who experienced cardiovascular events had greater increases in serum free testosterone levels than those who did not.
authors.affiliation: Department of Internal Medicine, Boston University School of Medicine, 670 Albany Street, Suite 205, Boston, MA 02118, USA. Shehzad.basaria@bmc.org
authors.forename: Shehzad
authors.initials: S
authors.lastname: Basaria
authors.forename: Maithili N
authors.initials: MN
authors.lastname: Davda
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Travison
authors.forename: Jagadish
authors.initials: J
authors.lastname: Ulloor
authors.forename: Ravinder
authors.initials: R
authors.lastname: Singh
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology*; D004958:Estradiol / Q000097:blood; D004970:Estrone / Q000097:blood; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051346:Mobility Limitation; D020097:Natriuretic Peptide, Brain / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012307:Risk Factors; D013739:Testosterone / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D020097:Natriuretic Peptide, Brain; D004970:Estrone; D013739:Testosterone; D004958:Estradiol; D005340:Fibrinogen; D002097:C-Reactive Protein