Improved prediction of all-cause mortality by a combination of serum total testosterone and insulin-like growth factor i in adult men

Nele Friedrich; Harald J. Schneider; Robin Haring; Matthias Nauck; Henry Völzke; Heyo K. Kroemer; Marcus Dörr; Jens Klotsche; Caroline Jung-Sievers; David Pittrow; Hendrik Lehnert; Winfried März; Lars Pieper; Hans Ulrich Wittchen; Henri Wallaschofski; Günter K. Stalla

doi:10.1016/j.steroids.2011.10.005

Improved prediction of all-cause mortality by a combination of serum total testosterone and insulin-like growth factor i in adult men

Nele Friedrich^*, Harald J. Schneider, Robin Haring, Matthias Nauck, Henry Völzke, Heyo K. Kroemer, Marcus Dörr, Jens Klotsche, Caroline Jung-Sievers, David Pittrow, Hendrik Lehnert, Winfried März, Lars Pieper, Hans Ulrich Wittchen, Henri Wallaschofski, Günter K. Stalla

^*Corresponding author for this work

Clinic of Internal Medicine I

9 Citations (Scopus)

Abstract

Objective: Lower levels of anabolic hormones in older age are well documented. Several studies suggested that low insulin-like growth factor I (IGF-I) or testosterone levels were related to increased mortality. The aim of the present study was to investigate the combined influence of low IGF-I and low testosterone on all-cause mortality in men. Methods and results: From two German prospective cohort studies, the DETECT study and SHIP, 3942 men were available for analyses. During 21,838 person-years of follow-up, 8.4% (n = 330) of men died. Cox model analyses with age as timescale and adjusted for potential confounders revealed that men with levels below the 10th percentile of at least one hormone [hazard ratio (HR) 1.38 (95% confidence-interval (CI) 1.06-1.78), p = 0.02] and two hormones [HR 2.88 (95% CI 1.32-6.29), p < 0.01] showed a higher risk of all-cause mortality compared to men with non-low hormones. The associations became non-significant by using the 20th percentile as cut-off showing that the specificity increased with lower cut-offs for decreased hormone levels. The inclusion of both IGF-I and total testosterone in a mortality prediction model with common risk factors resulted in a significant integrated discrimination improvement of 0.5% (95% CI 0.3-0.7%, p = 0.03). Conclusions: Our results prove that multiple anabolic deficiencies have a higher impact on mortality than a single anabolic deficiency and suggest that assessment of more than one anabolic hormone as a biomarker improve the prediction of all-cause mortality.

Original language	English
Journal	Steroids
Volume	77
Issue number	1-2
Pages (from-to)	52-58
Number of pages	7
ISSN	0039-128X
DOIs	https://doi.org/10.1016/j.steroids.2011.10.005
Publication status	Published - 01.01.2012

Funding

SHIP: This work is part of the research project Greifswald Approach to Individualized Medicine (GANI_MED). The GANI_MED consortium is funded by the Federal Ministry of Education and Research and the Ministry of Cultural Affairs of the Federal State of Mecklenburg – West Pomerania ( 03IS2061A ). SHIP is part of the Community Medicine Net ( http://www.medizin.uni-greifswald.de/icm ) of the University of Greifswald, which is funded by grants from the German Federal Ministry of Education and Research (BMBF, Grant 01ZZ96030, 01ZZ0701 ); the Ministry for Education, Research, and Cultural Affairs; and the Ministry for Social Affairs of the Federal State of Mecklenburg–West Pomerania. Novo Nordisc and Pfizer provided partial grant support for the determination of serum samples and data analysis. DETECT: Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment (DETECT) is a cross-sectional and prospective, longitudinal, nationwide clinical epidemiological study. DETECT is supported by an unrestricted educational grant from Pfizer GmbH, Karlsruhe, Germany . Members of the DETECT-Study group include: Principal investigator: Professor Dr. H.-U. Wittchen; Staff members: Dipl.-Psych. L. Pieper, Dipl.-Math. J. Klotsche, Dr. T. Eichler, Dr. H. Glaesmer, E. Katze. Steering Committee: Professor Dr. H. Lehnert (Lübeck), Professor Dr. G. K. Stalla (München), Professor Dr. A. M. Zeiher (Frankfurt); Advisory Board: Professor Dr. W. März (Heidelberg/Graz), Professor Dr. S. Silber (München), Professor Dr. Dr. U. Koch (Hamburg), Prof. Dr. D. Pittrow (München/Dresden), Professor Dr. M. Wehling (Mannheim), Dr. D. Leistner (Frankfurt), Priv.-Doz. Dr. H. J. Schneider (München), Dr. C. Sievers (München). Appendix A

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Friedrich, N., Schneider, H. J., Haring, R., Nauck, M., Völzke, H., Kroemer, H. K., Dörr, M., Klotsche, J., Jung-Sievers, C., Pittrow, D., Lehnert, H., März, W., Pieper, L., Wittchen, H. U., Wallaschofski, H., & Stalla, G. K. (2012). Improved prediction of all-cause mortality by a combination of serum total testosterone and insulin-like growth factor i in adult men. Steroids, 77(1-2), 52-58. https://doi.org/10.1016/j.steroids.2011.10.005

@article{37fc774d9fa2489c9c2bfc8a1ad12ab0,

title = "Improved prediction of all-cause mortality by a combination of serum total testosterone and insulin-like growth factor i in adult men",

abstract = "Objective: Lower levels of anabolic hormones in older age are well documented. Several studies suggested that low insulin-like growth factor I (IGF-I) or testosterone levels were related to increased mortality. The aim of the present study was to investigate the combined influence of low IGF-I and low testosterone on all-cause mortality in men. Methods and results: From two German prospective cohort studies, the DETECT study and SHIP, 3942 men were available for analyses. During 21,838 person-years of follow-up, 8.4\% (n = 330) of men died. Cox model analyses with age as timescale and adjusted for potential confounders revealed that men with levels below the 10th percentile of at least one hormone [hazard ratio (HR) 1.38 (95\% confidence-interval (CI) 1.06-1.78), p = 0.02] and two hormones [HR 2.88 (95\% CI 1.32-6.29), p < 0.01] showed a higher risk of all-cause mortality compared to men with non-low hormones. The associations became non-significant by using the 20th percentile as cut-off showing that the specificity increased with lower cut-offs for decreased hormone levels. The inclusion of both IGF-I and total testosterone in a mortality prediction model with common risk factors resulted in a significant integrated discrimination improvement of 0.5\% (95\% CI 0.3-0.7\%, p = 0.03). Conclusions: Our results prove that multiple anabolic deficiencies have a higher impact on mortality than a single anabolic deficiency and suggest that assessment of more than one anabolic hormone as a biomarker improve the prediction of all-cause mortality.",

author = "Nele Friedrich and Schneider, \{Harald J.\} and Robin Haring and Matthias Nauck and Henry V{\"o}lzke and Kroemer, \{Heyo K.\} and Marcus D{\"o}rr and Jens Klotsche and Caroline Jung-Sievers and David Pittrow and Hendrik Lehnert and Winfried M{\"a}rz and Lars Pieper and Wittchen, \{Hans Ulrich\} and Henri Wallaschofski and Stalla, \{G{\"u}nter K.\}",

year = "2012",

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doi = "10.1016/j.steroids.2011.10.005",

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Friedrich, N, Schneider, HJ, Haring, R, Nauck, M, Völzke, H, Kroemer, HK, Dörr, M, Klotsche, J, Jung-Sievers, C, Pittrow, D, Lehnert, H, März, W, Pieper, L, Wittchen, HU, Wallaschofski, H & Stalla, GK 2012, 'Improved prediction of all-cause mortality by a combination of serum total testosterone and insulin-like growth factor i in adult men', Steroids, vol. 77, no. 1-2, pp. 52-58. https://doi.org/10.1016/j.steroids.2011.10.005

TY - JOUR

T1 - Improved prediction of all-cause mortality by a combination of serum total testosterone and insulin-like growth factor i in adult men

AU - Friedrich, Nele

AU - Schneider, Harald J.

AU - Haring, Robin

AU - Nauck, Matthias

AU - Völzke, Henry

AU - Kroemer, Heyo K.

AU - Dörr, Marcus

AU - Klotsche, Jens

AU - Jung-Sievers, Caroline

AU - Pittrow, David

AU - Lehnert, Hendrik

AU - März, Winfried

AU - Pieper, Lars

AU - Wittchen, Hans Ulrich

AU - Wallaschofski, Henri

AU - Stalla, Günter K.

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Objective: Lower levels of anabolic hormones in older age are well documented. Several studies suggested that low insulin-like growth factor I (IGF-I) or testosterone levels were related to increased mortality. The aim of the present study was to investigate the combined influence of low IGF-I and low testosterone on all-cause mortality in men. Methods and results: From two German prospective cohort studies, the DETECT study and SHIP, 3942 men were available for analyses. During 21,838 person-years of follow-up, 8.4% (n = 330) of men died. Cox model analyses with age as timescale and adjusted for potential confounders revealed that men with levels below the 10th percentile of at least one hormone [hazard ratio (HR) 1.38 (95% confidence-interval (CI) 1.06-1.78), p = 0.02] and two hormones [HR 2.88 (95% CI 1.32-6.29), p < 0.01] showed a higher risk of all-cause mortality compared to men with non-low hormones. The associations became non-significant by using the 20th percentile as cut-off showing that the specificity increased with lower cut-offs for decreased hormone levels. The inclusion of both IGF-I and total testosterone in a mortality prediction model with common risk factors resulted in a significant integrated discrimination improvement of 0.5% (95% CI 0.3-0.7%, p = 0.03). Conclusions: Our results prove that multiple anabolic deficiencies have a higher impact on mortality than a single anabolic deficiency and suggest that assessment of more than one anabolic hormone as a biomarker improve the prediction of all-cause mortality.

AB - Objective: Lower levels of anabolic hormones in older age are well documented. Several studies suggested that low insulin-like growth factor I (IGF-I) or testosterone levels were related to increased mortality. The aim of the present study was to investigate the combined influence of low IGF-I and low testosterone on all-cause mortality in men. Methods and results: From two German prospective cohort studies, the DETECT study and SHIP, 3942 men were available for analyses. During 21,838 person-years of follow-up, 8.4% (n = 330) of men died. Cox model analyses with age as timescale and adjusted for potential confounders revealed that men with levels below the 10th percentile of at least one hormone [hazard ratio (HR) 1.38 (95% confidence-interval (CI) 1.06-1.78), p = 0.02] and two hormones [HR 2.88 (95% CI 1.32-6.29), p < 0.01] showed a higher risk of all-cause mortality compared to men with non-low hormones. The associations became non-significant by using the 20th percentile as cut-off showing that the specificity increased with lower cut-offs for decreased hormone levels. The inclusion of both IGF-I and total testosterone in a mortality prediction model with common risk factors resulted in a significant integrated discrimination improvement of 0.5% (95% CI 0.3-0.7%, p = 0.03). Conclusions: Our results prove that multiple anabolic deficiencies have a higher impact on mortality than a single anabolic deficiency and suggest that assessment of more than one anabolic hormone as a biomarker improve the prediction of all-cause mortality.

UR - https://www.scopus.com/pages/publications/83655167132

U2 - 10.1016/j.steroids.2011.10.005

DO - 10.1016/j.steroids.2011.10.005

M3 - Journal articles

C2 - 22037276

AN - SCOPUS:83655167132

SN - 0039-128X

VL - 77

SP - 52

EP - 58

JO - Steroids

JF - Steroids

IS - 1-2

ER -

Improved prediction of all-cause mortality by a combination of serum total testosterone and insulin-like growth factor i in adult men

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