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Original Research

Open Access

Time-varying testosterone level and risk of myocardial infarction and stroke among hypogonadal men: a longitudinal study in Germany

  • Xiao Zhang1
  • Hongwei Zhao1
  • Jennifer Horney2
  • Natalie Johnson3
  • Farid Saad4
  • Karim Sultan Haider5
  • Ahmad Haider5
  • Xiaohui Xu1,*,

1Department of Epidemiology and Biostatistics, Texas A&M University, College Station, TX 77843, USA

2College of Health Sciences, University of Delaware, Newark, DE 19716, USA

3Department of Environmental and Occupational Health, Texas A&M University, College Station, TX 77843, USA

4Research Department, Gulf Medical University, Ajman, United Arab Emirates

5Private Urology Practice, 27570 Bremerhaven, Germany

DOI: 10.31083/j.jomh1801023 Vol.18,Issue 1,January 2022 pp.1-8

Submitted: 09 March 2021 Accepted: 29 March 2021

Published: 31 January 2022

*Corresponding Author(s): Xiaohui Xu E-mail:


Background and objective: Findings on the association between testosterone and cardiovascular risk in men have been inconsistent. Previous studies investigated this association based on testosterone level measured at one single point in time (e.g., testosterone level at the baseline visit), which might not be relevant for the future cardiovascular events that occurred many years later, given the dynamic changes of testosterone level over time. Additionally, as compared to patients without prior cardiovascular history, those with prior cardiovascular events are more likely to have pathological changes in coronary or peripheral vasculature, and therefore more susceptible to cardiovascular events when exposed to risk factors. However, whether time-varying testosterone level affects differently between patients with prior cardiovascular events and those without is unknown. The objective of this study was to investigate the association between time-varying testosterone level and risks of myocardial infarction and stroke, and compared the associations stratified by patient’s prior cardiovascular event history. Material and methods: We used data of 376 hypogonadal men from a registry study in Germany with up to 11 years’ follow-up and applied Cox proportional hazards regression models to investigate the proposed association. Results: No association was found between baseline testosterone level and risks of myocardial infarction and stroke. When taking into account the changes of testosterone level over time and including testosterone as a time-varying covariate in the model, the adjusted hazard ratio (HR) for myocardial infarction associated with 1 nmol/L increase in testosterone level was 0.78 (95% CI: 0.64, 0.97); no association between time-varying testosterone level and stroke was found. The associations between testosterone level and cardiovascular risk were not different among patients with prior cardiovascular event history and those without. Conclusion: One baseline measurement of testosterone level may be insufficient to predict one’s future risk of cardiovascular events; regular monitoring of testosterone levels may be useful to assess the short-term cardiovascular risk in men.


Testosterone; Time-varying; Cardiovascular risk; Cohort; Longitudinal

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Xiao Zhang,Hongwei Zhao,Jennifer Horney,Natalie Johnson,Farid Saad,Karim Sultan Haider,Ahmad Haider,Xiaohui Xu. Time-varying testosterone level and risk of myocardial infarction and stroke among hypogonadal men: a longitudinal study in Germany. Journal of Men's Health. 2022. 18(1);1-8.


[1] Maas AHEM, Appelman YEA. Gender differences in coronary heart disease. Netherlands Heart Journal. 2010; 18: 598–603.

[2] Roth GA, Johnson C, Abajobir A, Abd-Allah F, Abera SF, Abyu G, et al. Global, Regional, and National Burden of Cardiovascu-lar Diseases for 10 Causes, 1990 to 2015. Journal of the Ameri-can College of Cardiology. 2017; 70: 1–25.

[3] Takov K, Wu J, Denvir MA, Smith LB, Hadoke PWF. The role of androgen receptors in atherosclerosis. Molecular and Cellular Endocrinology. 2018; 465: 82–91.

[4] Traish AM, Abdou R, Kypreos KE. Androgen deficiency and atherosclerosis: the lipid link. Vascular Pharmacology. 2009; 51: 303–313.

[5] Rezanezhad B, Borgquist R, Willenheimer R, Elzanaty S. The Association between Serum Testosterone and Risk Factors for Atherosclerosis. Current Urology. 2019; 13: 101–106.

[6] Rezanezhad B, Borgquist R, Willenheimer R, Elzanaty S. As-sociation between serum levels of testosterone and biomarkers of subclinical atherosclerosis. The Aging Male. 2018; 21: 182–186.

[7] Jones T, Kelly D. Randomized controlled trials—mechanistic studies of testosterone and the cardiovascular system. Asian Journal of Andrology. 2018; 20: 120.

[8] Lorigo M, Mariana M, Oliveira N, Lemos MC, Cairrao E. Vas-cular Pathways of Testosterone: Clinical Implications. Journal of Cardiovascular Translational Research. 2020; 13: 55–72.

[9] Wang A, Arver S, Boman K, Gerstein HC, Fu Lee S, Hess S, et al. Testosterone, sex hormone-binding globulin and risk of car-diovascular events: a report from the Outcome Reduction with an Initial Glargine Intervention trial. European Journal of Pre-ventive Cardiology. 2019; 26: 847–854.

[10] Haring R, Völzke H, Spielhagen C, Nauck M, Wallaschofski H. The role of sex hormone-binding globulin and testosterone in the risk of incident metabolic syndrome. European Journal of Preventive Cardiology. 2013; 20: 1061–1068.

[11] Basaria S. Male hypogonadism. Lancet. 2014; 383: 1250–1263.

[12] Huhtaniemi I, Forti G. Male late-onset hypogonadism: patho-genesis, diagnosis and treatment. Nature Reviews Urology. 2011; 8: 335–344.

[13] Kelly DM, Jones TH. Testosterone: a vascular hormone in health and disease. The Journal of Endocrinology. 2013; 217: R47–R71.

[14] Bruck B, Brehme U, Gugel N, Hanke S, Finking G, Lutz C, et al. Gender-specific differences in the effects of testosterone and estrogen on the development of atherosclerosis in rabbits. Arteriosclerosis, Thrombosis, and Vascular Biology. 1997; 17: 2192–2199.

[15] Vikan T, Johnsen SH, Schirmer H, Njølstad I, Svartberg J. Endogenous testosterone and the prospective association with carotid atherosclerosis in men: the Tromsø study. European Journal of Epidemiology. 2009; 24: 289–295.

[16] Soisson V, Brailly-Tabard S, Empana J, Féart C, Ryan J, Bertrand M, et al. Low plasma testosterone and elevated carotid intima-media thickness: importance of low-grade inflammation in elderly men. Atherosclerosis. 2012; 223: 244–249.

[17] Kwon H, Lee D, Kang HC, Lee JH. The relationship between testosterone, metabolic syndrome, and mean carotid intimamedia thickness in aging men. The Aging Male. 2014; 17: 211– 215.

[18] Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Predic-tion of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation. 2007; 115: 459–467.

[19] Nezu T, Hosomi N, Aoki S, Matsumoto M. Carotid Intima-Media Thickness for Atherosclerosis. Journal of Atherosclerosis and Thrombosis. 2016; 23: 18–31.

[20] O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK. Carotid-Artery Intima and Media Thickness as a Risk Factor for Myocardial Infarction and Stroke in Older Adults. New England Journal of Medicine. 2002; 340: 14–22.

[21] Gagliano-Jucá T, Basaria S. Testosterone replacement therapy and cardiovascular risk. Nature Reviews Cardiology. 2019; 16: 555–574.

[22] Srinath R, Hill Golden S, Carson KA, Dobs A. Endogenous testosterone and its relationship to preclinical and clinical mea-sures of cardiovascular disease in the atherosclerosis risk in communities study. The Journal of Clinical Endocrinology and Metabolism. 2015; 100: 1602–1608.

[23] Collet T, Ewing SK, Ensrud KE, Laughlin GA, Hoffman AR, Varosy PD, et al. Endogenous Testosterone Levels and the Risk of Incident Cardiovascular Events in Elderly Men: the MrOS Prospective Study. Journal of the Endocrine Society. 2020; 4: 1–15.

[24] Elagizi A, Köhler TS, Lavie CJ. Testosterone and Cardiovascu-lar Health. Mayo Clinic Proceedings. 2018; 93: 83–100.

[25] Bhasin S, Pencina M, Jasuja GK, Travison TG, Coviello A, Or-woll E, et al. Reference ranges for testosterone in men gener-ated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the Framingham Heart Study and applied to three geographi-cally distinct cohorts. The Journal of Clinical Endocrinology and Metabolism. 2011; 96: 2430–2439.

[26] Haider KS, Haider A, Doros G, Saad F. Design and Conduct of a Real-World Single-Center Registry Study on Testosterone Ther-apy of Men with Hypogonadism. Androgens: Clinical Research and Therapeutics. 2020; 2: 1–17.

[27] Yeap BB, Hyde Z, Almeida OP, Norman PE, Chubb SAP, Jam-rozik K, et al. Lower testosterone levels predict incident stroke and transient ischemic attack in older men. The Journal of Clin-ical Endocrinology and Metabolism. 2009; 94:2353–2359.

[28] Ohlsson C, Barrett-Connor E, Bhasin S, Orwoll E, Labrie F, Karlsson MK, et al. High serum testosterone is associated with reduced risk of cardiovascular events in elderly men. The MrOS (Osteoporotic Fractures in Men) study in Sweden. Journal of the American College of Cardiology. 2011; 58: 1674–1681.

[29] Magnani JW, Moser CB, Murabito JM, Sullivan LM, Wang N, Ellinor PT, et al. Association of sex hormones, aging, and atrial fibrillation in men: the Framingham Heart Study. Circulation: Arrhythmia and Electrophysiology. 2004; 7: 307–312.

[30] Arnlov J, Pencina MJ, Amin S, Nam BH, Benjamin EJ, Murabito JM, et al. Endogenous sex hormones and cardiovascular disease incidence in men. Annals of internal medicine. 2006; 145: 176–184.

[31] Abbott RD, Launer LJ, Rodriguez BL, Ross GW, Wilson PWF, Masaki KH, et al. Serum estradiol and risk of stroke in elderly men. Neurology. 2007; 68: 563–568.

[32] Shores MM, Arnold AM, Biggs ML, Longstreth JWT, Smith NL, Kizer JR, et al. Testosterone and dihydrotestosterone and incident ischaemic stroke in men in the Cardiovascular Health Study. Clinical endocrinology. 2014; 81: 746–753.

[33] Loo SY, Chen BY, Yu OHY, Azoulay L, Renoux C. Testosterone replacement therapy and the risk of stroke in men: a systematic review. Maturitas. 2017; 106: 31–37.

[34] Chmiel A, Mizia-Stec K, Wierzbicka-Chmiel J, Rychlik S, Muras A, Mizia M, et al. Low testosterone and sexual symptoms in men with acute coronary syndrome can be used to predict ma-jor adverse cardiovascular events during long-term follow-up. Andrology. 2015; 3: 1113–1118.

[35] Kelly DM, Akhtar S, Sellers DJ, Muraleedharan V, Channer KS, Jones TH. Testosterone differentially regulates targets of lipid and glucose metabolism in liver, muscle and adipose tissues of the testicular feminised mouse. Endocrine. 2016; 54: 504–515.

[36] Kelly DM, Nettleship JE, Akhtar S, Muraleedharan V, Sellers DJ, Brooke JC, et al. Testosterone suppresses the expression of regulatory enzymes of fatty acid synthesis and protects against hepatic steatosis in cholesterol-fed androgen deficient mice. Life Sciences. 2014; 109: 95–103.

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