Study finds associations between low testosterone and all-cause, CVD mortality

A recent meta-analysis found that low baseline serum testosterone concentrations are associated with an increased risk of all-cause and cardiovascular disease (CVD) mortality.^1,2

The primary outcome measures for the study were all-cause mortality, CVD death, and incident CVD events.

“This is a comprehensive analysis of relationships between testosterone concentrations and important health outcomes in men, with the results strengthened by the involvement of 11 cohort studies with 24,000 men across the age span from Australia, Europe, and North America, with testosterone measured accurately using mass spectrometry and longitudinal follow-up for outcomes,” said lead author Bu B. Yeap, MBBS, FRACP, PhD, in correspondence with Urology Times®. Yeap is a professor at the University of Western Australia Medical School and an endocrinologist at Fiona Stanley Hospital in Perth, Western Australia.

Overall, the study found that men with testosterone concentrations below 7.4 nmol/L (213 ng/dL) at baseline had a higher risk for all-cause mortality, even after adjusting for age, body mass index, lifestyle behaviors, and cardiovascular risk factors. An increased risk of all-cause mortality was also observed among those with luteinizing hormone (LH) concentrations above 10 IU/L at baseline and those with estradiol concentrations below 5.1 pmol/L at baseline.

Yeap added, “The association of lower testosterone concentrations with higher all-cause mortality was present irrespective of luteinizing hormone concentrations, indicating that low testosterone was the main factor (and not whether the low testosterone was due to testicular causes or centrally mediated). These results provide insights on testosterone concentrations expected in healthy men, additional to information from laboratory reference ranges.”

Data from the study also showed that men with testosterone concentrations below 5.3 nmol/L (153 ng/dL) at baseline had a higher risk of CVD mortality.

When assessing other sex hormone levels, investigators found that low testosterone coupled with normal or high levels of sex hormone-binding globulin (SHBG) was associated with an increased risk of mortality, but low testosterone and low SHBG was associated with a lower risk of mortality.

Beap noted, “This is consistent with the fact that men can have lower testosterone concentrations in the presence of low SHBG without being hypogonadal.”

Overall, men with lower baseline SHBG concentrations had lower all-cause mortality (aHR, 0.85; 95% CI, 0.77 to 0.95) and lower CVD mortality (aHR, 0.81; 95% CI, 0.65 to 1.00).

Conversely, lower dihydrotestosterone (DHT) concentrations at baseline were associated with higher all-cause mortality (aHR, 1.19; 95% CI, 1.08 to 1.30) and higher CVD mortality (aHR, 1.29; 95% CI, 1.03 to 1.61). The mortality risk increased for men with DHT concentrations above 2.45 nmol/L. Additionally, DHT concentrations below 0.59 nmol/L were associated with increased CVD events.

In total, investigators in the study analyzed 11 prospective cohort studies that included 24,109 men. Patients included in the studies assessed were community-dwelling men who had mass spectrometry done to measure total testosterone concentrations and had at least 5 years of follow-up.

The primary outcome measures for the study were all-cause mortality, CVD death, and incident CVD events. According to the authors, the findings from this study clarify previous inconsistent findings on the associations between sex hormones and these outcomes.

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. doi:10.7326/M23-2781

2. Low testosterone in men associated with higher risk for death. News release. May 7, 2024. Accessed May 15, 2024. https://www.newswise.com/articles/low-testosterone-in-men-associated-with-higher-risk-for-death