Article Impact Level: HIGH Data Quality: STRONG Summary of Nutrition, Metabolism and Cardiovascular Diseases, 104128. https://doi.org/10.1016/j.numecd.2025.104128 Dr. C Mary Schooling et al.
Points
- Researchers used Mendelian randomization to clarify the role of the hormone DHEA-s in aging because previous observational studies were inconclusive and lacked robust clinical trial data.
- The two-sample study analyzed large European genetic cohorts to determine the causal effects of DHEA-s on lifespan and key cardiometabolic health markers for both men and women.
- Genetically predicted higher DHEA-s levels were surprisingly associated with a shorter lifespan in men by 1.15 years, along with increased systolic and diastolic blood pressure.
- In stark contrast, the analysis found that genetically determined DHEA-s levels were not associated with any significant change in lifespan or blood pressure among the female participants studied.
- These findings suggest that DHEA has sexually dimorphic effects, prompting the authors to question its unregulated availability and recommend consideration of greater oversight to ensure public safety.
Summary
A two-sample Mendelian randomization study was conducted to assess the causal relationship between dehydroepiandrosterone sulfate (DHEA-s) and lifespan, as observational studies have been inconclusive and potentially confounded. Prior research suggested a possible link between DHEA-s and increased longevity in older men, but robust trial data on its safety or efficacy is absent. This study aimed to clarify the hormone’s role in lifespan and its effect on key biological determinants, including blood pressure, Apolipoprotein B (ApoB), and hemoglobin A1c (HbA1c), using a sex-specific genetic approach to minimize confounding variables.
The analysis leveraged sex-specific genetic data for DHEA-s from the Life-Adult/Life-Heart cohorts, which included 4,327 men and 3,501 women. These were assessed against lifespan outcomes from the UK Biobank, based on paternal (n = 415,311) and maternal (n = 412,937) attained age, along with other health markers (n = 167,020 men; n = 194,174 women). Using inverse variance weighted estimates, the study found genetically predicted DHEA-s was not associated with lifespan in women (0.04 years per logged μmol/L; 95% Confidence Interval [CI] -0.50 to 0.58). Conversely, higher DHEA-s was associated with a shorter lifespan in men (−1.15 years; 95% CI -1.72 to −0.58), a difference by sex that was statistically significant (p = 0.0017).
These findings indicate that DHEA-s has sexually dimorphic effects on longevity and cardiovascular risk factors. The hormone was positively associated with systolic and diastolic blood pressure in men but not in women and possibly associated with lower ApoB levels in men. The study’s conclusions challenge the perception of DHEA as a benign anti-aging supplement, particularly for men. Given its widespread availability as an unregulated product, the authors suggest that these results, which associate higher DHEA-s with reduced lifespan in men, warrant consideration for greater regulatory oversight to prevent potential public health harm.
Link to the article: https://www.nmcd-journal.com/article/S0939-4753(25)00282-0/abstract
References Schooling, C. M., & Zhao, J. V. (2025). Dehydroepiandrosterone sulfate on lifespan in men and women using Mendelian randomization. Nutrition, Metabolism and Cardiovascular Diseases, 104128. https://doi.org/10.1016/j.numecd.2025.104128
