Sex hormones and brain volumes in a longitudinal study of middle-aged men in the CARDIA study

Martine Elbejjani; Pamela J. Schreiner; David S. Siscovick; Stephen Sidney; Cora E. Lewis; Nick R. Bryan; Lenore J. Launer

doi:10.1002/brb3.765

Sex hormones and brain volumes in a longitudinal study of middle-aged men in the CARDIA study

Martine Elbejjani, Pamela J. Schreiner, David S. Siscovick, Stephen Sidney, Cora E. Lewis, Nick R. Bryan, Lenore J. Launer

Epidemiology & Community Health

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

6 Scopus citations

Abstract

Introduction: Several findings suggest that testosterone (T) is neuroprotective and that declining T levels during aging are associated with cognitive and brain pathologies; however, little is known on T and brain health in middle-age. We examined the relationships of total T, bioavailable T, and sex hormone binding globulin (SHBG) levels with total and regional gray matter (GM) and white matter (WM) volumes in middle-aged men. We also evaluated the association of sex hormone levels with cognitive function. Methods: Analysis included 267 community-dwelling men participating in the Coronary Artery Risk Development in Young Adults (CARDIA) brain magnetic resonance imaging (MRI) substudy. Total T, bioavailable T, and SHBG levels were measured at three times from the 2^nd to 4^th decade of life; brain volumes were measured at the ages of 42–56. Associations were estimated using linear regression models, adjusted for several potential confounders. Results: Higher SHBG levels were associated with greater total WM volume (+3.15 cm³ [95% confidence interval [CI] = 0.01, 6.28] per one standard deviation higher SHBG). Higher SHBG levels were associated with lower total and regional GM volumes overall and significantly with smaller parietal GM volume (−0.96 cm³ [95%CI = −1.71, −0.21]). T levels were not related to brain volumes. Neither T nor SHBG levels were associated with cognitive function. Conclusion: Results suggest a role for SHBG in structural brain outcomes in men and emphasize the value of investigating SHBG levels as modulators of sex hormone and metabolic pathways regulating brain and behavioral characteristics in men.

Original language	English (US)
Article number	e00765
Journal	Brain and Behavior
Volume	7
Issue number	10
DOIs	https://doi.org/10.1002/brb3.765
State	Published - Oct 2017

Bibliographical note

Funding Information:
The CARDIA study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201300025C & HHSN268201300026C), Northwestern University (HHSN268201300027C), University of Minnesota (HHSN268201300028C), Kaiser Foundation Research Institute (HHSN268201300029C), and Johns Hopkins University School of Medicine (HHSN268200900041C). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intraagency agreement between NIA and NHLBI (AG0005). This manuscript has been reviewed by CARDIA for scientific content.

Publisher Copyright:
Published 2017. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Keywords

MRI
brain volumes
men's health
sex hormone binding globulin
testosterone

Publisher link

10.1002/brb3.765

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651379

Find It

Find It at U of M Libraries

Cite this

@article{feb61c3496f446299f93c417d78e9bad,

title = "Sex hormones and brain volumes in a longitudinal study of middle-aged men in the CARDIA study",

abstract = "Introduction: Several findings suggest that testosterone (T) is neuroprotective and that declining T levels during aging are associated with cognitive and brain pathologies; however, little is known on T and brain health in middle-age. We examined the relationships of total T, bioavailable T, and sex hormone binding globulin (SHBG) levels with total and regional gray matter (GM) and white matter (WM) volumes in middle-aged men. We also evaluated the association of sex hormone levels with cognitive function. Methods: Analysis included 267 community-dwelling men participating in the Coronary Artery Risk Development in Young Adults (CARDIA) brain magnetic resonance imaging (MRI) substudy. Total T, bioavailable T, and SHBG levels were measured at three times from the 2nd to 4th decade of life; brain volumes were measured at the ages of 42–56. Associations were estimated using linear regression models, adjusted for several potential confounders. Results: Higher SHBG levels were associated with greater total WM volume (+3.15 cm3 [95% confidence interval [CI] = 0.01, 6.28] per one standard deviation higher SHBG). Higher SHBG levels were associated with lower total and regional GM volumes overall and significantly with smaller parietal GM volume (−0.96 cm3 [95%CI = −1.71, −0.21]). T levels were not related to brain volumes. Neither T nor SHBG levels were associated with cognitive function. Conclusion: Results suggest a role for SHBG in structural brain outcomes in men and emphasize the value of investigating SHBG levels as modulators of sex hormone and metabolic pathways regulating brain and behavioral characteristics in men.",

keywords = "MRI, brain volumes, men's health, sex hormone binding globulin, testosterone",

author = "Martine Elbejjani and Schreiner, {Pamela J.} and Siscovick, {David S.} and Stephen Sidney and Lewis, {Cora E.} and Bryan, {Nick R.} and Launer, {Lenore J.}",

note = "Funding Information: The CARDIA study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201300025C & HHSN268201300026C), Northwestern University (HHSN268201300027C), University of Minnesota (HHSN268201300028C), Kaiser Foundation Research Institute (HHSN268201300029C), and Johns Hopkins University School of Medicine (HHSN268200900041C). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intraagency agreement between NIA and NHLBI (AG0005). This manuscript has been reviewed by CARDIA for scientific content. Publisher Copyright: Published 2017. This article has been contributed to by US Government employees and their work is in the public domain in the USA.",

year = "2017",

month = oct,

doi = "10.1002/brb3.765",

language = "English (US)",

volume = "7",

journal = "Brain and Behavior",

issn = "2157-9032",

publisher = "John Wiley and Sons Inc.",

number = "10",

}

TY - JOUR

T1 - Sex hormones and brain volumes in a longitudinal study of middle-aged men in the CARDIA study

AU - Elbejjani, Martine

AU - Schreiner, Pamela J.

AU - Siscovick, David S.

AU - Sidney, Stephen

AU - Lewis, Cora E.

AU - Bryan, Nick R.

AU - Launer, Lenore J.

N1 - Funding Information: The CARDIA study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201300025C & HHSN268201300026C), Northwestern University (HHSN268201300027C), University of Minnesota (HHSN268201300028C), Kaiser Foundation Research Institute (HHSN268201300029C), and Johns Hopkins University School of Medicine (HHSN268200900041C). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intraagency agreement between NIA and NHLBI (AG0005). This manuscript has been reviewed by CARDIA for scientific content. Publisher Copyright: Published 2017. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

PY - 2017/10

Y1 - 2017/10

N2 - Introduction: Several findings suggest that testosterone (T) is neuroprotective and that declining T levels during aging are associated with cognitive and brain pathologies; however, little is known on T and brain health in middle-age. We examined the relationships of total T, bioavailable T, and sex hormone binding globulin (SHBG) levels with total and regional gray matter (GM) and white matter (WM) volumes in middle-aged men. We also evaluated the association of sex hormone levels with cognitive function. Methods: Analysis included 267 community-dwelling men participating in the Coronary Artery Risk Development in Young Adults (CARDIA) brain magnetic resonance imaging (MRI) substudy. Total T, bioavailable T, and SHBG levels were measured at three times from the 2nd to 4th decade of life; brain volumes were measured at the ages of 42–56. Associations were estimated using linear regression models, adjusted for several potential confounders. Results: Higher SHBG levels were associated with greater total WM volume (+3.15 cm3 [95% confidence interval [CI] = 0.01, 6.28] per one standard deviation higher SHBG). Higher SHBG levels were associated with lower total and regional GM volumes overall and significantly with smaller parietal GM volume (−0.96 cm3 [95%CI = −1.71, −0.21]). T levels were not related to brain volumes. Neither T nor SHBG levels were associated with cognitive function. Conclusion: Results suggest a role for SHBG in structural brain outcomes in men and emphasize the value of investigating SHBG levels as modulators of sex hormone and metabolic pathways regulating brain and behavioral characteristics in men.

AB - Introduction: Several findings suggest that testosterone (T) is neuroprotective and that declining T levels during aging are associated with cognitive and brain pathologies; however, little is known on T and brain health in middle-age. We examined the relationships of total T, bioavailable T, and sex hormone binding globulin (SHBG) levels with total and regional gray matter (GM) and white matter (WM) volumes in middle-aged men. We also evaluated the association of sex hormone levels with cognitive function. Methods: Analysis included 267 community-dwelling men participating in the Coronary Artery Risk Development in Young Adults (CARDIA) brain magnetic resonance imaging (MRI) substudy. Total T, bioavailable T, and SHBG levels were measured at three times from the 2nd to 4th decade of life; brain volumes were measured at the ages of 42–56. Associations were estimated using linear regression models, adjusted for several potential confounders. Results: Higher SHBG levels were associated with greater total WM volume (+3.15 cm3 [95% confidence interval [CI] = 0.01, 6.28] per one standard deviation higher SHBG). Higher SHBG levels were associated with lower total and regional GM volumes overall and significantly with smaller parietal GM volume (−0.96 cm3 [95%CI = −1.71, −0.21]). T levels were not related to brain volumes. Neither T nor SHBG levels were associated with cognitive function. Conclusion: Results suggest a role for SHBG in structural brain outcomes in men and emphasize the value of investigating SHBG levels as modulators of sex hormone and metabolic pathways regulating brain and behavioral characteristics in men.

KW - MRI

KW - brain volumes

KW - men's health

KW - sex hormone binding globulin

KW - testosterone

UR - http://www.scopus.com/inward/record.url?scp=85030243584&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85030243584&partnerID=8YFLogxK

U2 - 10.1002/brb3.765

DO - 10.1002/brb3.765

M3 - Article

C2 - 29075555

AN - SCOPUS:85030243584

SN - 2157-9032

VL - 7

JO - Brain and Behavior

JF - Brain and Behavior

IS - 10

M1 - e00765

ER -

Sex hormones and brain volumes in a longitudinal study of middle-aged men in the CARDIA study

Abstract

Bibliographical note

Keywords

Publisher link

Find It

Other files and links

Fingerprint

Cite this