Association of Testosterone and Sex Hormone-binding Globulin with Incident CVD Events

Pavankumar Kamat


January 05, 2022


  • Low total testosterone level was not associated with a higher risk of myocardial infarction (MI), ischaemic stroke (IS), haemorrhagic stroke (HS), heart failure (HF), and major adverse cardiovascular events (MACE).

  • Low calculated free testosterone (cFT) or free testosterone (FTZ) was associated with a marginally lower risk of MACE.

  • Men with low sex hormone-binding globulin (SHBG) levels had a higher risk of MI but a lower risk of IS and HF.

Why this matters

  • Whether differences in testosterone levels increase the incidence of cardiovascular events in middle-aged and older men remains controversial.

Study design

  • A cohort study included 210,700 men (age, 40-69 years), identified from the UK Biobank (2006-2010).

  • Primary outcome: incident cardiovascular disease (CVD) events (hospitalisations or deaths where the primary diagnosis was MI, HS, IS, and HF).

  • Secondary outcome: MACE (nonfatal MI, IS, and CVD deaths).

  • Funding: Western Australian Health Translation Network; Medical Research Future Fund; Lawley Pharmaceuticals.

Key results

  • During the follow-up, 8790 men (4.2%) reported an MI, HS, IS, HF, and MACE event and 10,318 (4.9%) died.

  • After adjustment for confounders, lower total testosterone level (quintile 1 vs 5) was not associated with an increased risk of (adjusted HR [aHR]; 95% CI):

    • MI (0.89; 0.80-1.00);

    • HS (0.94; 0.70-1.26);

    • IS (0.95; 0.82-1.10);

    • HF (1.15; 0.91-1.45); and

    • MACE (0.92; 0.84-1.00).

  • Men with lower cFT or FTZ level (quintile 1 vs 5) had a lower risk of (aHR; 95% CI):

    • MI (0.86; 0.79-0.95); and

    • MACE (0.90; 0.84-0.97).

  • Lower SHBG level (quintile 1 vs 5) was associated with a higher risk of MI (aHR, 1.23; 95% CI, 1.09-1.38) and a lower risk of IS (aHR, 0.79; 95% CI, 0.67-0.94) and HF (aHR, 0.69; 95% CI, 0.54-0.89).

  • Lower SHBG level (quintile 1 vs 5) was not associated with a higher risk of HS (aHR, 0.81; 95% CI, 0.57-1.14) and MACE (aHR, 1.01; 95% CI, 0.92-1.11).


  • Observational study.

Yeap BB, Marriott RJ, Antonio L, Raj S, Dwivedi G, Reid CM, Anawalt BD, Bhasin S, Dobs AS, Handelsman DJ, Hankey GJ, Haring R, Matsumoto AM, Norman PE, O'Neill TW, Ohlsson C, Orwoll ES, Vanderschueren D, Wittert GA, Wu FCW, Murray K. Associations of Serum Testosterone and Sex Hormone-Binding Globulin With Incident Cardiovascular Events in Middle-Aged to Older Men. Ann Intern Med. 2021 Dec 28 [Epub ahead of print]. doi: 10.7326/M21-0551. PMID: 34958606  View abstract.


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