Low Testosterone Tracked With Higher Death Risk in Men

CATEGORY: MEN’S HEALTH

Testosterone is usually discussed in terms of energy, muscle and sex drive. The number carries more than that. A 2024 analysis pooled the raw data from nine long-running studies of men. Those whose baseline testosterone sat below 213 nanograms per deciliter, a standard blood-test unit, had a higher risk of dying from any cause over the following years. Below 153 nanograms per deciliter, the raised risk was specifically of death from cardiovascular disease, meaning disease of the heart and blood vessels.¹

Raw Data From Nine Cohorts, Not Nine Summaries

Most pooled analyses stack up other people’s published conclusions. This one went back to the individual records, a design called an individual-participant-data meta-analysis, which lets one consistent set of definitions run across every study. Nine prospective cohorts of community-dwelling men went in, from Australia, Europe and North America. Each followed its participants for at least 5 years. Together that came to more than 255,000 person-years, with summary results from eleven further studies covering 24,109 men layered on top. Hormone levels were measured by mass spectrometry, the most accurate laboratory method available, which matters in a field where older and less precise tests muddied earlier work.¹ Death from any cause, cardiovascular death and new cardiovascular events were named as the main outcomes in advance.¹

Two Cutoffs, 213 and 153

The two thresholds behaved differently. Below 213, the higher risk of death applied to any cause, and it held regardless of where other hormone levels sat. Below 153, the risk that rose was cardiovascular. Both associations survived adjustment for age, weight, smoking, blood pressure, diabetes and cholesterol. A low reading carried information the standard risk factors had not already supplied.¹

Testosterone Is Not a Routine Checkup Measure

Testosterone is not part of a standard checkup for most men. A low level therefore goes unrecorded much of the time, until symptoms or disease bring it into view. Several symptoms tend to prompt a test: persistent fatigue, low libido, loss of muscle or bone strength, depressed mood and difficulty concentrating. Obesity or type 2 diabetes alongside them makes testing likelier still.

Testosterone Treatment Did Not Lower Major Heart Events

An association is not a lever. A low level may be a downstream signal of obesity, poor metabolic health or chronic illness. Those conditions carry risk of their own. An earlier systematic review pooling 11 studies of more than 16,000 men also linked low testosterone to higher death from any cause, though the results scattered widely between studies.² The trial evidence is where the distinction bites. In men with low levels and high heart risk, testosterone treatment did not lower the rate of major heart events compared with a placebo, an inactive dummy treatment.³

Key Takeaways

• In pooled individual data from nine cohorts, death from any cause was more likely below about 213 ng/dL of testosterone, and cardiovascular death more likely below about 153 ng/dL.
• Those associations held after accounting for age, weight, smoking, blood pressure, diabetes and cholesterol, so the reading added information beyond the standard risk factors.
• A randomized trial found that testosterone treatment did not reduce major heart events in men with low levels and high heart risk, which fits a marker rather than a cause.

References

1. Yeap BB, Marriott RJ, Dwivedi G, et al. Associations of testosterone and related hormones with all-cause and cardiovascular mortality and incident cardiovascular disease in men: individual participant data meta-analyses. Ann Intern Med. 2024 Jun;177(6):768-781. link
2. Araujo AB, Dixon JM, Suarez EA, et al. Endogenous testosterone and mortality in men: a systematic review and meta-analysis. The Journal of Clinical Endocrinology & Metabolism. 2011;96(10):3007–3019. link.
3. Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular safety of testosterone-replacement therapy. The New England Journal of Medicine. 2023;389(2):107–117. link.