Sex-specific associations of circulating testosterone levels with all-cause and cause-specific mortality

in European Journal of Endocrinology
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  • 1 Department of Epidemiology and Biostatistics, International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
  • 2 Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  • 3 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  • 4 Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
  • 5 Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
  • 6 State Key Laboratory of Reproductive Medicine, Center for Global Health, Nanjing Medical University, Nanjing, China
  • 7 Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China

Correspondence should be addressed to D Hang; Email: hangdong@njmu.edu.cn
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Objective

Testosterone is a critical determinant of health in both genders. However, the relationship between circulating levels of testosterone and mortality remains undetermined.

Methods

We examined the associations of serum total testosterone (TT) and free testosterone (FT) with all-cause and cause-specific mortality in 154 965 men and 93 314 postmenopausal women from UK Biobank. Cox regression models were used to calculate the hazard ratios (HR) and 95% CIs. Given multiple testing, P < 0.005 was considered statistically significant.

Results

Over a median follow-up of 8.9 (inter-quartile range: 8.3–9.5) years, we documented 5754 deaths in men, including 1243 (21.6%) from CVD and 2987 (51.9%) from cancer. In postmenopausal women, 2435 deaths occurred, including 346 (14.2%) from CVD and 1583 (65.0%) from cancer. TT and FT concentrations were inversely associated with all-cause mortality in men, with the multivariable HR of 0.82 (95% CI: 0.75–0.91) and 0.80 (95% CI: 0.73–0.87) for the highest (Q5) vs the lowest quintile (Q1), respectively. In postmenopausal women, TT concentrations showed a positive association with all-cause mortality (HR for Q5 vs Q1 = 1.20, 95% CI: 1.06–1.37). Furthermore, higher TT and FT concentrations were associated with a lower risk of cancer mortality in men (both P for trend = 0.001), whereas TT concentrations were suggestively associated with a higher risk of cancer mortality in postmenopausal women (P for trend = 0.03).

Conclusions

Our findings suggest that high levels of circulating testosterone may be beneficial for all-cause and cancer mortality in men but detrimental in postmenopausal women.

Supplementary Materials

    • Supplementary Figure 1
    • Supplementary Figure 2
    • Supplementary Figure 3
    • Supplementary Figure 4
    • Supplementary Figure 5
    • Supplementary Figure 6
    • Supplementary Table 1. The disease composition of all-cause mortality
    • Supplementary Table 2. Test of the proportional hazards assumption for the fully-adjusted Cox regression models
    • Supplementary Table 3. Age-adjusted Spearman correlation coefficients between serum total testosterone, free testosterone, sex hormone binding globulin, and body mass index in men (in gray) and postmenopausal women (in white), respectively
    • Supplementary Table 4. Associations of serum total and free testosterone concentrations with all-cause and cause-specific mortality in men
    • Supplementary Table 5. Associations of serum total and free testosterone concentrations with all-cause and cause-specific mortality in postmenopausal women
    • Supplementary Table 6. Associations of serum total and free testosterone concentrations with all-cause and cause-specific mortality in 51,448 postmenopausal women who never used hormone replacement therapy
    • Supplementary Table 7. Associations of serum sex hormone binding globulin concentrations with all-cause and cause-specific mortality in men and postmenopausal women
    • Supplementary Table 8. Associations of serum total and free testosterone concentrations with cancer-specific mortality in mena
    • Supplementary Table 9. Associations of serum total and free testosterone concentrations with cancer-specific mortality in postmenopausal womena
    • Supplementary Table 10. Associations of serum total and free testosterone concentrations with other-cause mortality in men
    • Supplementary Table 11. Associations of serum total and free testosterone concentrations with other-cause mortality in postmenopausal women
    • Supplementary Table 12. Associations of serum total and free testosterone concentrations with all-cause and cause-specific mortality in men after excluding 617 men within two years of follow-up time
    • Supplementary Table 13. Associations of serum total and free testosterone concentrations with all-cause and cause-specific mortality in postmenopausal women after excluding 241 women within two years of follow-up time
    • Supplementary Table 14. Associations of serum total and free testosterone concentrations with all-cause and cause-specific mortality in men after excluding 4,809 men who self-rated poor overall health at baseline
    • Supplementary Table 15. Associations of serum total and free testosterone concentrations with all-cause and cause-specific mortality in postmenopausal women after excluding 2,073 women who self-rated poor overall health at baseline

 

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