Serum testosterone is inversely, and sex hormone-binding globulin directly, associated with all-cause mortality in men

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

doi:10.1210/clinem/dgaa743

Serum testosterone is inversely, and sex hormone-binding globulin directly, associated with all-cause mortality in men

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

Research output: Contribution to journal › Article › peer-review

32 Citations (Scopus)

65 Downloads (Pure)

Abstract

CONTEXT: Serum testosterone concentrations decline with age, while serum sex hormone-binding globulin (SHBG) concentrations increase.

OBJECTIVE: To analyse 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 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 complete case analysis of 149,436 men with 10,053 deaths (1,925 CVD and 4,927 cancer-related), men with lower testosterone had higher mortality 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 lower mortality 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, 3,128 CVD and 7,468 cancer-related) and analysis excluding deaths within first two years (9,261, 1,734 and 4,534 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.

Original language	English
Pages (from-to)	E625-E637
Number of pages	13
Journal	The Journal of clinical endocrinology and metabolism
Volume	106
Issue number	2
Early online date	16 Oct 2020
DOIs	https://doi.org/10.1210/clinem/dgaa743
Publication status	Published - 1 Feb 2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1210/clinem/dgaa743

Yeap, et al., 2020 Serum testosterone is inverselyAccepted author manuscript, 1.36 MB

Cite this

Yeap, B. B., Marriott, R. J., Antonio, L., Chan, Y. X., Raj, S., Dwivedi, G., Reid, C. M., Anawalt, B. D., Bhasin, S., Dobs, A. S., Hankey, G. J., Matsumoto, A. M., Norman, P. E., O'Neill, T. W., Ohlsson, C., Orwoll, E. S., Vanderschueren, D., Wittert, G. A., Wu, F. C. W., & Murray, K. (2021). Serum testosterone is inversely, and sex hormone-binding globulin directly, associated with all-cause mortality in men. The Journal of clinical endocrinology and metabolism, 106(2), E625-E637. https://doi.org/10.1210/clinem/dgaa743

@article{64d7aea187dc414a970e5f192d47b432,

title = "Serum testosterone is inversely, and sex hormone-binding globulin directly, associated with all-cause mortality in men",

abstract = "CONTEXT: Serum testosterone concentrations decline with age, while serum sex hormone-binding globulin (SHBG) concentrations increase.OBJECTIVE: To analyse 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 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 complete case analysis of 149,436 men with 10,053 deaths (1,925 CVD and 4,927 cancer-related), men with lower testosterone had higher mortality 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 lower mortality 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, 3,128 CVD and 7,468 cancer-related) and analysis excluding deaths within first two years (9,261, 1,734 and 4,534 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.",

keywords = "Cancer, Cardiovascular disease, Mortality, Sex hormone-binding globulin, Testosterone",

author = "Yeap, {Bu B} and Marriott, {Ross J} and Leen Antonio and Chan, {Yi X} and Suchitra Raj and Girish Dwivedi and Reid, {Christopher M} and Anawalt, {Bradley D} and Shalender Bhasin and Dobs, {Adrian S} and Hankey, {Graeme J} and Matsumoto, {Alvin M} and Norman, {Paul E} and O'Neill, {Terence W} and Claes Ohlsson and Orwoll, {Eric S} and Dirk Vanderschueren and Wittert, {Gary A} and Wu, {Frederick C W} and Kevin Murray",

year = "2021",

month = feb,

day = "1",

doi = "10.1210/clinem/dgaa743",

language = "English",

volume = "106",

pages = "E625--E637",

journal = "The Journal of clinical endocrinology and metabolism",

issn = "0021-972X",

publisher = "ENDOCRINE SOC",

number = "2",

}

Yeap, BB , Marriott, RJ, Antonio, L, Chan, YX, Raj, S, Dwivedi, G, Reid, CM, Anawalt, BD, Bhasin, S, Dobs, AS, Hankey, GJ, Matsumoto, AM, Norman, PE, O'Neill, TW, Ohlsson, C, Orwoll, ES, Vanderschueren, D, Wittert, GA, Wu, FCW & Murray, K 2021, 'Serum testosterone is inversely, and sex hormone-binding globulin directly, associated with all-cause mortality in men', The Journal of clinical endocrinology and metabolism, vol. 106, no. 2, pp. E625-E637. https://doi.org/10.1210/clinem/dgaa743

TY - JOUR

T1 - Serum testosterone is inversely, and sex hormone-binding globulin directly, associated with all-cause mortality in men

AU - Yeap, Bu B

AU - Marriott, Ross J

AU - Antonio, Leen

AU - Chan, Yi X

AU - Raj, Suchitra

AU - Dwivedi, Girish

AU - Reid, Christopher M

AU - Anawalt, Bradley D

AU - Bhasin, Shalender

AU - Dobs, Adrian S

AU - Hankey, Graeme J

AU - Matsumoto, Alvin M

AU - Norman, Paul E

AU - O'Neill, Terence W

AU - Ohlsson, Claes

AU - Orwoll, Eric S

AU - Vanderschueren, Dirk

AU - Wittert, Gary A

AU - Wu, Frederick C W

AU - Murray, Kevin

PY - 2021/2/1

Y1 - 2021/2/1

N2 - CONTEXT: Serum testosterone concentrations decline with age, while serum sex hormone-binding globulin (SHBG) concentrations increase.OBJECTIVE: To analyse 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 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 complete case analysis of 149,436 men with 10,053 deaths (1,925 CVD and 4,927 cancer-related), men with lower testosterone had higher mortality 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 lower mortality 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, 3,128 CVD and 7,468 cancer-related) and analysis excluding deaths within first two years (9,261, 1,734 and 4,534 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.

AB - CONTEXT: Serum testosterone concentrations decline with age, while serum sex hormone-binding globulin (SHBG) concentrations increase.OBJECTIVE: To analyse 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 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 complete case analysis of 149,436 men with 10,053 deaths (1,925 CVD and 4,927 cancer-related), men with lower testosterone had higher mortality 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 lower mortality 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, 3,128 CVD and 7,468 cancer-related) and analysis excluding deaths within first two years (9,261, 1,734 and 4,534 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.

KW - Cancer

KW - Cardiovascular disease

KW - Mortality

KW - Sex hormone-binding globulin

KW - Testosterone

UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=uwapure5-25&SrcAuth=WosAPI&KeyUT=WOS:000759115900045&DestLinkType=FullRecord&DestApp=WOS_CPL

U2 - 10.1210/clinem/dgaa743

DO - 10.1210/clinem/dgaa743

M3 - Article

C2 - 33059368

SN - 0021-972X

VL - 106

SP - E625-E637

JO - The Journal of clinical endocrinology and metabolism

JF - The Journal of clinical endocrinology and metabolism

IS - 2

ER -

Serum testosterone is inversely, and sex hormone-binding globulin directly, associated with all-cause mortality in men

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Supplement to “Serum testosterone is inversely, and sex hormone-binding globulin directly, associated with all-cause mortality in men”.

Cite this

Serum testosterone is inversely, and sex hormone-binding globulin directly, associated with all-cause mortality in men

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Datasets

Supplement to “Serum testosterone is inversely, and sex hormone-binding globulin directly, associated with all-cause mortality in men”.

Cite this