The association is well documented. The causal direction never was. Men with cardiovascular disease, obesity and metabolic dysfunction tend to have lower testosterone — and that single observation was used to argue two incompatible positions for the better part of a decade.
One camp read it as: low testosterone contributes to cardiovascular disease, so treatment should help. The other read the 2010–2013 safety signals as: treatment causes cardiovascular events. Neither position was supported by evidence capable of establishing causation.
The three explanations an association permits
Low testosterone contributes to cardiovascular disease. The optimistic reading.
Cardiovascular disease and its correlates lower testosterone. Reverse causation, and entirely plausible — chronic illness suppresses the hypothalamic-pituitary-gonadal axis, and adiposity is independently associated with lower testosterone.
Something drives both. Obesity, metabolic syndrome and inflammation are associated with lower testosterone and with cardiovascular disease, which would produce the observed correlation with no direct link between the two.
Observational data cannot distinguish these. The relationship between androgens and obesity in particular has been reviewed as its own subject,[1] and the direction of causation there is a live question rather than a settled one — see the bidirectional trap.
Why the observational evidence was so hard to use
Men prescribed testosterone differ systematically from men who are not — in symptom burden, comorbidity, and how often they see a doctor. Statistical adjustment handles measured differences; it cannot handle unmeasured ones. The problem runs in both directions: the same design that produced an alarming signal in 2013 produced a reassuring one in 83,010 veterans, where normalised testosterone tracked with roughly half the mortality — an effect no randomised trial has reproduced.
That is the central limitation of the 2013 JAMA analysis reporting an association between testosterone therapy and mortality, myocardial infarction and stroke.[2] It is an association in a population that was not randomly assigned.
What randomisation resolved
TRAVERSE removed the confounding by randomising 5,204 men with hypogonadism and cardiovascular disease or increased risk to testosterone or placebo, and found testosterone non-inferior to placebo for major adverse cardiac events.[3]
Note what that resolves and what it does not. It answers: does giving testosterone to these men increase cardiac events? — no. It does not answer: why do men with heart disease have lower testosterone? The association remains; the treatment question is settled separately from it.
A contemporary review of what the recent landmark trials mean for practice in older men sets out that distinction in more depth.[4]
What follows clinically
Low testosterone is a finding to explain, not just a number to correct. The guideline recommends additional diagnostic evaluation to ascertain the cause of a confirmed androgen deficiency before treating.[5]
Contributors are often modifiable. Adiposity, poor sleep, chronic illness and certain medications all lower testosterone, and several respond to treatment on their own terms.
Treatment is not a cardiovascular intervention. TRAVERSE found non-inferiority, not benefit.[3] Nobody should be starting testosterone to protect their heart.
Frequently asked questions
Does low testosterone cause heart disease? Not established. The association is well documented; the direction is not, and reverse causation is a strong candidate.
Will treating low testosterone improve my cardiovascular risk? No trial supports that. TRAVERSE found non-inferiority for major adverse cardiac events.[3]
Should I have my testosterone checked because I have heart disease? Testing is indicated by symptoms plus the diagnostic pathway, not by cardiovascular status alone — see why one low result doesn't mean low testosterone.
Next in this series
Thirteen years of argument, one trial, and a labelling change in 2025. What does it change for the man deciding this week?
Continue with what TRAVERSE means for TRT today.
References
5 sources
- Allan CA, McLachlan RI. Androgens and obesity. Curr Opin Endocrinol Diabetes Obes. 2010;17(3):224–232. doi:10.1097/MED.0b013e3283398ee2 · PMID 20418719
- Vigen R, O'Donnell CI, Barón AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310(17):1829–1836. doi:10.1001/jama.2013.280386 · PMID 24193080
- Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. N Engl J Med. 2023;389(2):107–117. doi:10.1056/NEJMoa2215025 · PMID 37326322
- Grossmann M, Anawalt BD, Yeap BB. Testosterone therapy in older men: clinical implications of recent landmark trials. Eur J Endocrinol. 2024;191(1):R22–R31. doi:10.1093/ejendo/lvae071 · PMID 38917356
- Bhasin S, Brito JP, Cunningham GR, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744. doi:10.1210/jc.2018-00229 · PMID 29562364
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