Causal effects of serum testosterone on septic shock mortality: a Mendelian randomization study
Main finding · 28-day survival per 1-SD increase in testosterone PGSResult — go to the resultAdjusted hazard ratio 0.72Authors' conclusion
Genetically determined higher testosterone levels are causally associated with improved survival in patients with septic shock, particularly in men and in those with lipid dysmetabolism.
Study context
- Population
- Patients with septic shock in multicentre ICUs
- Participants
- 469 patients
- Comparison
- Genetically predicted testosterone and 28-day mortality
- Outcome
- 28-day mortality
- Follow-up
- 28 days
Methodological detailsmulticentre, polygenic score, two-sample Mendelian randomization
- Multicentre
- Polygenic score
- Two-sample Mendelian randomization
Main finding
As reported in the abstract
28-day survival per 1-SD increase in testosterone PGS
Adjusted hazard ratio
0.72
P = 0.024
Further findings
| Outcome | Reduction in mortality hazard | P value |
|---|---|---|
| Mortality hazard, high vs low testosterone PGS (Kaplan-Meier) | 54.2% | log-rank P = 0.007 |
28-day mortality, men (subgroup)
- HR per 1-SD increase in testosterone polygenic score (PGS), men
- HR, 0.66; P = 0.020
28-day mortality, women (subgroup)
- HR per 1-SD increase in testosterone PGS, women
- HR, 0.78; P = 0.37
Two-sample Mendelian randomization
- Causality confirmed (inverse variance-weighted β), consistent across complementary estimation methods
- β = - 2.79; P = 0.0042
Effect modification by apolipoprotein C3 (ApoC3) levels (subgroup)
- Testosterone-protective effect significantly modified by ApoC3, stronger at higher ApoC3
- interaction, P = 0.041
- HR at high ApoC3 levels
- 0.51 (95% CI 0.31-0.85)
Original publication
Causal effects of serum testosterone on septic shock mortality: a Mendelian randomization study. Crit Care. Published 23 January 2026. doi:10.
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