Sex-Specific Associations of Testosterone and Genetic Factors With Health Span
Abstract
BACKGROUND: Previous studies have suggested associations between testosterone, genetic factors, and a series of complex diseases, but the associations with the lifespan phenotype, such as health span, remain unclear.
METHODS: In this prospective cohort study, we analyzed 145,481 men and 147,733 women aged 38-73 years old from UK Biobank (UKB) to investigate the sex-specific associations of total testosterone (TT), free testosterone (FT), or polygenic risk score (PRS) with health span termination (HST) risk. At baseline, serum testosterone levels were measured. HST was defined by eight events strongly associated with longevity. PRS, an efficient tool combining the effect of common genetic variants to discriminate genetic risk of complex phenotypes, was constructed by 12 single-nucleotide polymorphisms related to health span from UKB (P ≤ 5.0 × 10-8). We used multivariable Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).
RESULTS: With a median follow-up time of 7.70 years, 26,748 (18.39%) men and 18,963 (12.84%) women had HST. TT was negatively associated with HST in men [HR per standard deviation (SD) increment of log-TT: 0.92, 95% CI: 0.88-0.97]. Inversely, both TT (HR per SD increment of log-TT: 1.05, 95% CI: 1.02-1.08) and FT (HR per SD increment of log-FT: 1.08, 95% CI: 1.05-1.11) presented an increased risk of HST in women. PRS was positively associated with HST risk (quintile 5 versus quintile 1, men, HR: 1.19, 95% CI: 1.15-1.24;…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 147,733 participants or records.
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