Investigating the association of testosterone with survival in men and women using a Mendelian randomization study in the UK Biobank

Abstract Life expectancy in the developed West is currently stagnated and remains shorter in men than women. Well-established evolutionary biology theory suggests lifespan trades-off against reproductive success, possibly sex-specifically. We examined whether a key driver of reproductive success, te...

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Autores principales:	C. M. Schooling, J. V. Zhao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8fa42ad1c5b34c33ba51906d6ebf6f15
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spelling	oai:doaj.org-article:8fa42ad1c5b34c33ba51906d6ebf6f152021-12-02T18:33:57ZInvestigating the association of testosterone with survival in men and women using a Mendelian randomization study in the UK Biobank10.1038/s41598-021-93360-z2045-2322https://doaj.org/article/8fa42ad1c5b34c33ba51906d6ebf6f152021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93360-zhttps://doaj.org/toc/2045-2322Abstract Life expectancy in the developed West is currently stagnated and remains shorter in men than women. Well-established evolutionary biology theory suggests lifespan trades-off against reproductive success, possibly sex-specifically. We examined whether a key driver of reproductive success, testosterone, affected survival using a Mendelian randomization longevity study in the UK Biobank to obtain unbiased estimates, along with control exposures. We applied published genetic instruments for testosterone to obtain inverse variance weighted estimates of associations with survival to (i.e., age at) recruitment, in 167,020 men and 194,174 women. We similarly obtained estimates for a positive control (smoking initiation), and a negative control (absorbate), a marker of vitamin C metabolism. Testosterone was associated with poorer survival (0.10 years younger at recruitment per effect size of testosterone, 95% confidence interval (CI) 0.004 to 0.20). As expected, smoking initiation was also associated with poorer survival (0.37 years younger, 95% CI 0.25 to 0.50), but not absorbate (0.01 years younger, 95% CI − 0.09 to 0.11). Several aspects of a healthy lifestyle (low animal fat diet) and several widely used medications (statins, metformin, dexamethasone and possibly aspirin) may modulate testosterone. Explicitly designing interventions sex-specifically based on these insights might help address stagnating life expectancy and sexual disparities.C. M. SchoolingJ. V. ZhaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-6 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q C. M. Schooling J. V. Zhao Investigating the association of testosterone with survival in men and women using a Mendelian randomization study in the UK Biobank
description	Abstract Life expectancy in the developed West is currently stagnated and remains shorter in men than women. Well-established evolutionary biology theory suggests lifespan trades-off against reproductive success, possibly sex-specifically. We examined whether a key driver of reproductive success, testosterone, affected survival using a Mendelian randomization longevity study in the UK Biobank to obtain unbiased estimates, along with control exposures. We applied published genetic instruments for testosterone to obtain inverse variance weighted estimates of associations with survival to (i.e., age at) recruitment, in 167,020 men and 194,174 women. We similarly obtained estimates for a positive control (smoking initiation), and a negative control (absorbate), a marker of vitamin C metabolism. Testosterone was associated with poorer survival (0.10 years younger at recruitment per effect size of testosterone, 95% confidence interval (CI) 0.004 to 0.20). As expected, smoking initiation was also associated with poorer survival (0.37 years younger, 95% CI 0.25 to 0.50), but not absorbate (0.01 years younger, 95% CI − 0.09 to 0.11). Several aspects of a healthy lifestyle (low animal fat diet) and several widely used medications (statins, metformin, dexamethasone and possibly aspirin) may modulate testosterone. Explicitly designing interventions sex-specifically based on these insights might help address stagnating life expectancy and sexual disparities.
format	article
author	C. M. Schooling J. V. Zhao
author_facet	C. M. Schooling J. V. Zhao
author_sort	C. M. Schooling
title	Investigating the association of testosterone with survival in men and women using a Mendelian randomization study in the UK Biobank
title_short	Investigating the association of testosterone with survival in men and women using a Mendelian randomization study in the UK Biobank
title_full	Investigating the association of testosterone with survival in men and women using a Mendelian randomization study in the UK Biobank
title_fullStr	Investigating the association of testosterone with survival in men and women using a Mendelian randomization study in the UK Biobank
title_full_unstemmed	Investigating the association of testosterone with survival in men and women using a Mendelian randomization study in the UK Biobank
title_sort	investigating the association of testosterone with survival in men and women using a mendelian randomization study in the uk biobank
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8fa42ad1c5b34c33ba51906d6ebf6f15
work_keys_str_mv	AT cmschooling investigatingtheassociationoftestosteronewithsurvivalinmenandwomenusingamendelianrandomizationstudyintheukbiobank AT jvzhao investigatingtheassociationoftestosteronewithsurvivalinmenandwomenusingamendelianrandomizationstudyintheukbiobank
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Investigating the association of testosterone with survival in men and women using a Mendelian randomization study in the UK Biobank

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