title: Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men.
abstract: OBJECTIVE
  There is a significant uncertainty regarding the effect of testosterone replacement therapy (TRT) on cardiovascular (CV) outcomes including myocardial infarction (MI) and stroke. The aim of this study was to examine the relationship between normalization of total testosterone (TT) after TRT and CV events as well as all-cause mortality in patients without previous history of MI and stroke.
  
  
  RESULTS
  We retrospectively examined 83 010 male veterans with documented low TT levels. The subjects were categorized into (Gp1: TRT with resulting normalization of TT levels), (Gp2: TRT without normalization of TT levels) and (Gp3: Did not receive TRT). By utilizing propensity score-weighted Cox proportional hazard models, the association of TRT with all-cause mortality, MI, stroke, and a composite endpoint was compared between these groups. The all-cause mortality [hazard ratio (HR): 0.44, confidence interval (CI) 0.42-0.46], risk of MI (HR: 0.76, CI 0.63-0.93), and stroke (HR: 0.64, CI 0.43-0.96) were significantly lower in Gp1 (n = 43 931, median age = 66 years, mean follow-up = 6.2 years) vs. Gp3 (n = 13 378, median age = 66 years, mean follow-up = 4.7 years) in propensity-matched cohort. Similarly, the all-cause mortality (HR: 0.53, CI 0.50-0.55), risk of MI (HR: 0.82, CI 0.71-0.95), and stroke (HR: 0.70, CI 0.51-0.96) were significantly lower in Gp1 vs. Gp2 (n = 25 701, median age = 66 years, mean follow-up = 4.6 years). There was no difference in MI or stroke risk between Gp2 and Gp3.
  
  
  CONCLUSIONS
  In this large observational cohort with extended follow-up, normalization of TT levels after TRT was associated with a significant reduction in all-cause mortality, MI, and stroke.
authors.affiliation: Division of Cardiovascular Research, Kansas City VA Medical Center, Kansas City, MO, USA.
authors.forename: Rishi
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Division of Cardiovascular Research, Kansas City VA Medical Center, Kansas City, MO, USA.
authors.forename: Olurinde A
authors.initials: OA
authors.lastname: Oni
authors.affiliation: Division of Cardiovascular Diseases, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Kamal
authors.initials: K
authors.lastname: Gupta
authors.affiliation: Division of Health Services Research, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Chen
authors.affiliation: Division of Cardiovascular Research, Kansas City VA Medical Center, Kansas City, MO, USA.
authors.forename: Mukut
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Division of Cardiovascular Diseases, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Buddhadeb
authors.initials: B
authors.lastname: Dawn
authors.affiliation: Division of Cardiovascular Research, Kansas City VA Medical Center, Kansas City, MO, USA.
authors.forename: Ram
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Division of Cardiovascular Diseases, University of Kansas Medical Center, Kansas City, KS, USA Division of Cardiovascular Medicine, Kansas City VA Medical Center, 4801 E. Linwood Boulevard, Kansas City, MO 64128, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Parashara
authors.affiliation: Division of Nephrology, Kansas City VA Medical Center, Kansas City, MO, USA.
authors.forename: Virginia J
authors.initials: VJ
authors.lastname: Savin
authors.affiliation: Division of Cardiovascular Medicine, University of California San Francisco, Fresno, CA, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Ambrose
authors.affiliation: Division of Cardiovascular Research, Kansas City VA Medical Center, Kansas City, MO, USA Division of Cardiovascular Diseases, University of Kansas Medical Center, Kansas City, KS, USA Division of Cardiovascular Medicine, Kansas City VA Medical Center, 4801 E. Linwood Boulevard, Kansas City, MO 64128, USA rajat.barua@va.gov.
authors.forename: Rajat S
authors.initials: RS
authors.lastname: Barua
mesh_terms: D000368:Aged; D000728:Androgens / Q000008:administration & dosage; D004333:Drug Administration Routes; D020249:Hormone Replacement Therapy / Q000401:mortality; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000401:mortality* / Q000517:prevention & control; D011446:Prospective Studies; D012189:Retrospective Studies; D020521:Stroke / Q000097:blood / Q000401:mortality / Q000517:prevention & control; D013739:Testosterone / Q000008:administration & dosage / Q000097:blood* / Q000172:deficiency; D014481:United States / Q000453:epidemiology
chemical_list: D000728:Androgens; D013739:Testosterone
keywords: Myocardial infarction; Stroke; Testosterone replacement therapy