| Title: | Serum Testosterone is Inversely and Sex Hormone-binding Globulin is Directly Associated with All-cause Mortality in Men. |
| Journal: | The Journal of Clinical Endocrinology & Metabolism |
| Published: | 16 Oct 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33059368/ |
| DOI: | https://doi.org/10.1210/clinem/dgaa743 |
| URL: | https://academic.oup.com/jcem/article-pdf/106/2/e625/41849364/dgaa743.pdf |
Publication 5712
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Abstract
CONTEXT: Serum testosterone concentrations decline with age, while serum sex hormone-binding globulin (SHBG) concentrations increase. OBJECTIVE: To analyze associations of baseline serum testosterone and SHBG concentrations, and calculated free testosterone (cFT) values, with all-cause and cause-specific mortality in men. DESIGN, SETTING, AND PARTICIPANTS: The UK Biobank prospective cohort study of community-dwelling men aged 40-69 years old, followed for 11 years. MAIN OUTCOME MEASURES: All-cause, atherosclerotic cardiovascular disease (CVD) and cancer-related mortality. Cox proportional hazards regression was performed, adjusting for age, waist circumference, medical conditions, and other covariates. Models for testosterone included SHBG and vice versa. RESULTS: In a complete case analysis of 149 436 men with 10 053 deaths (1925 CVD and 4927 cancer-related), men with lower testosterone had a higher mortality rate from any cause (lowest vs highest quintile, Q1 vs Q5, fully-adjusted hazard ratio [HR] = 1.14, 95% confidence interval [CI] = 1.06-1.22, overall trend P < 0.001), and cancer (HR = 1.20, CI = 1.09-1.33, P < 0.001), with no association for CVD deaths. Similar results were seen for cFT. Men with lower SHBG had a lower mortality rate from any cause (Q1 vs Q5, HR = 0.68, CI = 0.63-0.73, P < 0.001), CVD (HR = 0.70, CI = 0.59-0.83, P < 0.001), and cancer (HR = 0.80, CI = 0.72-0.89, P < 0.001). A multiply imputed dataset (N = 208 425, 15 914 deaths, 3128 CVD-related and 7468 cancer-related) and analysis excluding deaths within the first 2 years (9261, 1734, and 4534 events) yielded similar results. CONCLUSIONS: Lower serum testosterone is independently associated with higher all-cause and cancer-related, but not CVD-related, mortality in middle-aged to older men. Lower SHBG is independently associated with lower all-cause, CVD-related, and cancer-related mortality. Confirmation and determination of causality requires mechanistic studies and prospective trials.20 Authors
- Bu B Yeap
- Ross J Marriott
- Leen Antonio
- Yi X Chan
- Suchitra Raj
- Girish Dwivedi
- Christopher M Reid
- Bradley D Anawalt
- Shalender Bhasin
- Adrian S Dobs
- Graeme J Hankey
- Alvin M Matsumoto
- Paul E Norman
- Terence W O'Neill
- Claes Ohlsson
- Eric S Orwoll
- Dirk Vanderschueren
- Gary A Wittert
- Frederick C W Wu
- Kevin Murray
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