title: Impact of Testosterone Replacement Therapy on Myocardial Infarction, Stroke, and Death in Men With Low Testosterone Concentrations in an Integrated Health Care System.
abstract: The aim of this study was to assess the effect of testosterone replacement therapy (TRT) on cardiovascular outcomes. Men (January 1, 1996, to December 31, 2011) with a low initial total testosterone concentration, a subsequent testosterone level, and >3 years of follow-up were studied. Levels were correlated with testosterone supplement use. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of death, nonfatal myocardial infarction, and stroke at 3 years. Multivariate adjusted hazard ratios (HRs) comparing groups of persistent low (<212 ng/dl, n = 801), normal (212 to 742 ng/dl, n = 2,241), and high (>742 ng/dl, n = 1,694) achieved testosterone were calculated by Cox hazard regression. A total of 4,736 men were studied. Three-year rates of MACE and death were 6.6% and 4.3%, respectively. Subjects supplemented to normal testosterone had reduced 3-year MACE (HR 0.74; 95% confidence interval [CI] 0.56 to 0.98, p = 0.04) compared to persistently low testosterone, driven primarily by death (HR 0.65, 95% CI 0.47 to 0.90). HRs for MI and stroke were 0.73 (95% CI 0.40 to 1.34), p = 0.32, and 1.11 (95% CI 0.54 to 2.28), p = 0.78, respectively. MACE was noninferior but not superior for high achieved testosterone with no benefit on MI and a trend to greater stroke risk. In conclusion, in a large general health care population, TRT to normal levels was associated with reduced MACE and death over 3 years but a stroke signal with high achieved levels suggests a conservative approach to TRT.
authors.affiliation: Intermountain Heart Institute, Intermountain Medical Center, Murray, Utah; University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Anderson
authors.affiliation: Intermountain Heart Institute, Intermountain Medical Center, Murray, Utah. Electronic address: heidi.may@imail.org.
authors.forename: Heidi T
authors.initials: HT
authors.lastname: May
authors.affiliation: Intermountain Heart Institute, Intermountain Medical Center, Murray, Utah.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Lappé
authors.affiliation: Intermountain Heart Institute, Intermountain Medical Center, Murray, Utah.
authors.forename: Tami
authors.initials: T
authors.lastname: Bair
authors.affiliation: Intermountain Heart Institute, Intermountain Medical Center, Murray, Utah.
authors.forename: Viet
authors.initials: V
authors.lastname: Le
authors.affiliation: Intermountain Heart Institute, Intermountain Medical Center, Murray, Utah; University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: John F
authors.initials: JF
authors.lastname: Carlquist
authors.affiliation: Intermountain Heart Institute, Intermountain Medical Center, Murray, Utah; University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Muhlestein
mesh_terms: D015415:Biomarkers / Q000097:blood*; D002423:Cause of Death / Q000639:trends; D019033:Delivery of Health Care, Integrated; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000188:drug therapy*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000453:epidemiology* / Q000517:prevention & control; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000453:epidemiology* / Q000517:prevention & control; D015996:Survival Rate / Q000639:trends; D013739:Testosterone / Q000008:administration & dosage* / Q000097:blood; D013997:Time Factors; D014589:Utah / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D013739:Testosterone