Advertisement

Relation of Testosterone Normalization to Mortality and Myocardial Infarction in Men With Previous Myocardial Infarction

      The effect of normalization of serum testosterone levels with testosterone replacement therapy (TRT) in patients with a history of myocardial infarction (MI) is unknown. The objective of this study was to determine the incidence of recurrent MI and all-cause mortality in subjects with a history of MI and low total testosterone (TT) with and without TRT. We retrospectively examined 1,470 men with documented low TT levels and previous MI, categorized into Gp1: TRT with normalization of TT levels (n = 755) Gp2: TRT without normalization of TT levels (n = 542), and Gp3: no TRT (n = 173). The association of TRT with all-cause mortality and recurrent MI was compared using propensity score-weighted Cox proportional hazard models. All-cause mortality was lower in Gp1 versus Gp2 (hazard ratio [HR] 0.76, confidence interval [CI] 0.64 to 0.90, p = 0.002), and Gp1 versus Gp3 (HR 0.76, CI 0.60 to 0.98, p = 0.031). There was no significant difference in the risk of death between Gp2 versus Gp3 (HR 0.97, CI 0.76 to 1.24, p = 0.81). Adjusted regression analyses showed no significant differences in the risk of recurrent MI between groups (Gp1 vs Gp3, HR 0.79, CI 0.12 to 5.27, p = 0.8; Gp1 vs Gp2 HR 1.10, CI 0.25 to 4.77, p = 0.90; Gp2 vs Gp3 HR 0.58, CI 0.08 to 4.06, p = 0.58). In conclusion, in a large observational cohort of male veterans with previous MI, normalization of TT levels with TRT was associated with decreased all-cause mortality compared with those with non-normalized TT levels and the untreated group. Furthermore, in this high-risk population, TRT was not associated with an increased risk of recurrent MI.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Araujo AB
        • O'Donnell AB
        • Brambilla DJ
        • Simpson WB
        • Longcope C
        • Matsumoto AM
        • McKinlay JB
        Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study.
        J Clin Endocrinol Metab. 2004; 89: 5920-5926
        • Baillargeon J
        • Urban RJ
        • Ottenbacher KJ
        • Pierson KS
        • Goodwin JS
        Trends in androgen prescribing in the United States, 2001 to 2011.
        JAMA Intern Med. 2013; 173: 1465-1466
        • Haddad RM
        • Kennedy CC
        • Caples SM
        • Tracz MJ
        • Boloña ER
        • Sideras K
        • Uraga MV
        • Erwin PJ
        • Montori VM
        Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials.
        Mayo Clin Proc. 2007; 82: 29-39
        • Shores MM
        • Smith NL
        • Forsberg CW
        • Anawalt BD
        • Matsumoto AM
        Testosterone treatment and mortality in men with low testosterone levels.
        J Clin Endocrinol Metab. 2012; 97: 2050-2058
        • Maggi M
        • Wu FC
        • Jones TH
        • Jackson G
        • Behre HM
        • Hackett G
        • Martin-Morales A
        • Balercia G
        • Dobs AS
        • Arver ST
        • Maggio M
        • Cunningham GR
        • Isidori AM
        • Quinton R
        • Wheaton OA
        • Siami FS
        • Rosen RC
        • RHYME Investigators
        Testosterone treatment is not associated with increased risk of adverse cardiovascular events: results from the Registry of Hypogonadism in Men (RHYME).
        Int J Clin Pract. 2016; 70: 843-852
        • Cheetham TC
        • An J
        • Jacobsen SJ
        • Niu F
        • Sidney S
        • Quesenberry CP
        • VanDenEeden SK
        Association of testosterone replacement with cardiovascular outcomes among men with androgen deficiency.
        JAMA Intern Med. 2017; 177: 491-499
        • Anderson JL
        • May HT
        • Lappé DL
        • Bair T
        • Le V
        • Carlquist JF
        • Muhlestein JB
        Impact of testosterone replacement therapy on myocardial infarction, stroke, and death in men with low testosterone concentrations in an integrated health care system.
        Am J Cardiol. 2016; 117: 794-799
        • Basaria S
        • Coviello AD
        • Travison TG
        • Storer TW
        • Farwell WR
        • Jette AM
        • Eder R
        • Tennstedt S
        • Ulloor J
        • Zhang A
        • Choong K
        • Lakshman KM
        • Mazer NA
        • Miciek R
        • Krasnoff J
        • Elmi A
        • Knapp PE
        • Brooks B
        • Appleman E
        • Aggarwal S
        • Bhasin G
        • Hede-Brierley L
        • Bhatia A
        • Collins L
        • LeBrasseur N
        • Fiore LD
        • Bhasin S
        Adverse events associated with testosterone administration.
        N Engl J Med. 2010; 363: 109-122
        • Vigen R
        • O'Donnell CI
        • Barón AE
        • Grunwald GK
        • Maddox TM
        • Bradley SM
        • Barqawi A
        • Woning G
        • Wierman ME
        • Plomondon ME
        • Rumsfeld JS
        • Ho PM
        Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels.
        JAMA. 2013; 310: 1829-1836
        • Finkle WD
        • Greenland S
        • Ridgeway GK
        • Adams JL
        • Frasco MA
        • Cook MB
        • Fraumeni Jr., JF
        • Hoover RN
        Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men.
        PLoS One. 2014; 9: e85805
        • Sharma R
        • Oni OA
        • Gupta K
        • Chen G
        • Sharma M
        • Dawn B
        • Sharma R
        • Parashara D
        • Savin VJ
        • Ambrose JA
        • Barua RS
        Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men.
        Eur Heart J. 2015; 36: 2706-2715
        • Motivala AA
        • Tamhane U
        • Ramanath VS
        • Saab F
        • Montgomery DG
        • Fang J
        • Kline-Rogers E
        • May N
        • Ng G
        • Froehlich J
        • Gurm H
        • Eagle KA
        A prior myocardial infarction: how does it affect management and outcomes in recurrent acute coronary syndromes?.
        Clin Cardiol. 2008; 31: 590-596
      1. VA Informatics and Computing Infrastructure (VINCI). Accessible at:http://www.hsrd.research.va.gov/for_researchers/vinci/default.cfm. Accessed on May 26, 2019.

        • Byrd JB
        • Vigen R
        • Plomondon ME
        • Rumsfeld JS
        • Box TL
        • Fihn SD
        • Maddox TM
        Data quality of an electronic health record tool to support VA cardiac catheterization laboratory quality improvement: the VA Clinical Assessment, Reporting, and Tracking System for Cath Labs (CART) program.
        Am Heart J. 2013; 165: 434-440
        • Wang C
        • Catlin DH
        • Demers LM
        • Starcevic B
        • Swerdloff RS
        Measurement of total serum testosterone in adult men: comparison of current laboratory methods versus liquid chromatography-tandem mass spectrometry.
        J Clin Endocrinol Metab. 2004; 89: 534-543
        • Vesper HW
        • Botelho JC
        Standardization of testosterone measurements in humans.
        J Steroid Biochem Mol Biol. 2010; 121: 513-519
        • Lazarou S
        • Reyes-vallejo L
        • Morgentaler A
        Wide variability in laboratory reference values for serum testosterone.
        J Sex Med. 2006; 3: 1085-1089
        • Rosner W
        • Auchus RJ
        • Azziz R
        • Sluss PM
        • Raff H
        Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement.
        J Clin Endocrinol Metab. 2007; 92: 405-413
      2. The VA Medicare Vital Status File. Available at: http://www.virec.research.va.gov Accessed on May 26, 2019.

      3. The Social Security Administration (SSA) Death Master File. Accessible at: https://www.ssa.gov/dataexchange/request_dmf.html. Accessed on May 26, 2019.

        • Austin PC
        An introduction to propensity score methods for reducing the effects of confounding in observational studies.
        Multivariate Behav Res. 2011; 46: 399-424
        • Jones TH
        • Kelly DM
        Randomized controlled trials – mechanistic studies of testosterone and the cardiovascular system.
        Asian J Androl. 2018; 20: 120-130
        • English KM
        • Steeds RP
        • Jones TH
        • Diver MJ
        • Channer KS
        Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: a randomized, double-blind, placebo-controlled study.
        Circulation. 2000; 102: 1906-1911
        • Malkin CJ
        • Pugh PJ
        • Morris PD
        • Kerry KE
        • Jones RD
        • Jones TH
        • Channer KS
        Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life.
        Heart. 2004; 90: 871-876
        • Basaria S
        • Harman SM
        • Travison TG
        • Hodis H
        • Tsitouras P
        • Budoff M
        • Pencina KM
        • Vita J
        • Dzekov C
        • Mazer NA
        • Coviello AD
        • Knapp PE
        • Hally K
        • Pinjic E
        • Yan M
        • Storer TW
        • Bhasin S
        Effects of testosterone administration for 3 years on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels: a randomized clinical trial.
        JAMA. 2015; 314: 570-581
        • Alexander GC
        • Iyer G
        • Lucas E
        • Lin D
        • Singh S
        Cardiovascular risks of exogenous testosterone use among men: a systematic review and meta-analysis.
        Am J Med. 2017; 130: 293-305
        • Budoff MJ
        • Ellenberg SS
        • Lewis CE
        • 3rd Mohler ER
        • Wenger NK
        • Bhasin S
        • Barrett-Connor E
        • Swerdloff RS
        • Stephens-Shields A
        • Cauley JA
        • Crandall JP
        • Cunningham GR
        • Ensrud KE
        • Gill TM
        • Matsumoto AM
        • Molitch ME
        • Nakanishi R
        • Nezarat N
        • Matsumoto S
        • Hou X
        • Basaria S
        • Diem SJ
        • Wang C
        • Cifelli D
        • Snyder PJ
        Testosterone treatment and coronary artery plaque volume in older men with low testosterone.
        JAMA. 2017; 317: 708-716
        • Bhasin S
        • Brito JP
        • Cunningham GR
        • Hayes FJ
        • Hodis HN
        • Matsumoto AM
        • Snyder PJ
        • Swerdloff RS
        • Wu FC
        • Yialamas MA
        Testosterone therapy in men with hypogonadism: an endocrine society clinical practice guideline.
        J Clin Endocrinol Metab. 2018; 103: 1715-1744
        • Khera M
        • Adaikan G
        • Buvat J
        • Carrier S
        • El-Meliegy A
        • Hatzimouratidis K
        • McCullough A
        • Morgentaler A
        • Torres LO
        • Salonia A
        Diagnosis and treatment of testosterone deficiency: recommendations from the Fourth International Consultation for Sexual Medicine (ICSM 2015).
        J Sex Med. 2016; 13: 1787-1804
        • Channer KS
        Endogenous testosterone levels and cardiovascular disease in healthy men.
        Heart. 2011; 97: 867-869
        • Mulhall JP
        • Trost LW
        • Brannigan RE
        • Kurtz EG
        • Redmon JB
        • Chiles KA
        • Lightner DJ
        • Miner MM
        • Murad MH
        • Nelson CJ
        • Platz EA
        • Ramanathan LV
        • Lewis RW
        Evaluation and management of testosterone deficiency: AUA guideline.
        J Urol. 2018; 200: 423-432
        • Kapoor D
        • Goodwin E
        • Channer KS
        • Jones TH
        Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes.
        Eur J Endocrinol. 2006; 154: 899-906