Sex Differences in the Association Between Serum Testosterone and Kidney Function in the General Population

Anna C. van der Burgh; Elif Aribas; M. Arfan Ikram; Maryam Kavousi; Sebastian J.C.M.M. Neggers; Ewout J. Hoorn; Layal Chaker

doi:10.1016/j.ekir.2023.04.015

Sex Differences in the Association Between Serum Testosterone and Kidney Function in the General Population

Anna C. van der Burgh
, Elif Aribas
, M. Arfan Ikram
, Maryam Kavousi
, Sebastian J.C.M.M. Neggers
, Ewout J. Hoorn
, Layal Chaker^*

^*Corresponding author for this work

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

7 Citations (Scopus)

237 Downloads (Pure)

Abstract

Introduction: Testosterone might prevent kidney function decline, although evidence is limited in men and lacking in women from the general population. We investigated the association between serum testosterone and kidney function in men and women from a large population-based cohort study. Methods: Participants aged ≥45 years with available measurements of serum testosterone, sex hormone-binding globulin (SHBG), creatinine, and cystatine C were included. Assessments of kidney function included baseline assessments of the estimated glomerular filtration rate (eGFR) based on serum creatinine (eGFRcreat) or serum cystatin C (eGFRcys), and the urine albumin-to-creatinine ratio (ACR), and repeated assessments of eGFRcreat. Linear regression and linear mixed models were used to assess the associations of serum free and total testosterone with kidney function, stratified for sex. Results: A total of 4095 men and 5389 women (mean age 65.2 years) were included. In men, higher free testosterone was associated with lower eGFRcreat (beta −0.63, 95% confidence interval [CI]: −1.05; −0.21), higher eGFRcys (beta 0.56, 95% CI: 0.07; 1.05), and lower ACR (beta −0.25, 95% CI: −0.35; −0.16) at baseline. Higher total testosterone was associated with higher baseline and follow-up eGFRcreat, and with lower eGFRcreat when additionally adjusted for SHBG. In women, higher free testosterone was associated with lower baseline eGFRcreat and eGFRcys (beta −1.03, 95% CI: −1.36; −0.71; beta −1.07, 95% CI: −1.44; −0.70; respectively) and lower eGFRcreat over time (beta −0.78, 95% CI: −1.10; −0.46), but not with ACR. Conclusions: eGFRcys might be a better parameter than eGFRcreat for the association of testosterone with kidney function, although further studies investigating this are needed. Furthermore, we identified sex differences in the association between testosterone and kidney function, with a positive association in men and a negative association in women.

Original language	English
Pages (from-to)	1342-1351
Number of pages	10
Journal	Kidney International Reports
Volume	8
Issue number	7
DOIs	https://doi.org/10.1016/j.ekir.2023.04.015
Publication status	Published - Jul 2023

Bibliographical note

Funding Information:
We gratefully acknowledge the dedication, commitment, and contribution of the study participants, the staff of the Rotterdam Study, and the participating general practitioners and pharmacists. The Rotterdam Study is funded by the Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands, Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. None of the funders had any role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The datasets analyzed during the current study are not publicly available because of legal and ethical restraints. Data are available from the corresponding author on reasonable request. Conceptualization was done by ACB, EJH, and LC. Methodology was done by ACB and LC. Formal analysis and investigation were conducted by ACB. Writing-original draft preparation was done by ACB. Writing-review and editing were done by ACB, EA, MAI, MK, SN, EJH, and LC. Supervision was by EJH and LC.

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© 2023 International Society of Nephrology

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Cite this

@article{1455cc3b9f844155aaa3a22249e9fead,

title = "Sex Differences in the Association Between Serum Testosterone and Kidney Function in the General Population",

abstract = "Introduction: Testosterone might prevent kidney function decline, although evidence is limited in men and lacking in women from the general population. We investigated the association between serum testosterone and kidney function in men and women from a large population-based cohort study. Methods: Participants aged ≥45 years with available measurements of serum testosterone, sex hormone-binding globulin (SHBG), creatinine, and cystatine C were included. Assessments of kidney function included baseline assessments of the estimated glomerular filtration rate (eGFR) based on serum creatinine (eGFRcreat) or serum cystatin C (eGFRcys), and the urine albumin-to-creatinine ratio (ACR), and repeated assessments of eGFRcreat. Linear regression and linear mixed models were used to assess the associations of serum free and total testosterone with kidney function, stratified for sex. Results: A total of 4095 men and 5389 women (mean age 65.2 years) were included. In men, higher free testosterone was associated with lower eGFRcreat (beta −0.63, 95\% confidence interval [CI]: −1.05; −0.21), higher eGFRcys (beta 0.56, 95\% CI: 0.07; 1.05), and lower ACR (beta −0.25, 95\% CI: −0.35; −0.16) at baseline. Higher total testosterone was associated with higher baseline and follow-up eGFRcreat, and with lower eGFRcreat when additionally adjusted for SHBG. In women, higher free testosterone was associated with lower baseline eGFRcreat and eGFRcys (beta −1.03, 95\% CI: −1.36; −0.71; beta −1.07, 95\% CI: −1.44; −0.70; respectively) and lower eGFRcreat over time (beta −0.78, 95\% CI: −1.10; −0.46), but not with ACR. Conclusions: eGFRcys might be a better parameter than eGFRcreat for the association of testosterone with kidney function, although further studies investigating this are needed. Furthermore, we identified sex differences in the association between testosterone and kidney function, with a positive association in men and a negative association in women.",

author = "\{van der Burgh\}, \{Anna C.\} and Elif Aribas and Ikram, \{M. Arfan\} and Maryam Kavousi and Neggers, \{Sebastian J.C.M.M.\} and Hoorn, \{Ewout J.\} and Layal Chaker",

note = "Funding Information: We gratefully acknowledge the dedication, commitment, and contribution of the study participants, the staff of the Rotterdam Study, and the participating general practitioners and pharmacists. The Rotterdam Study is funded by the Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands, Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. None of the funders had any role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The datasets analyzed during the current study are not publicly available because of legal and ethical restraints. Data are available from the corresponding author on reasonable request. Conceptualization was done by ACB, EJH, and LC. Methodology was done by ACB and LC. Formal analysis and investigation were conducted by ACB. Writing-original draft preparation was done by ACB. Writing-review and editing were done by ACB, EA, MAI, MK, SN, EJH, and LC. Supervision was by EJH and LC. Publisher Copyright: {\textcopyright} 2023 International Society of Nephrology",

year = "2023",

month = jul,

doi = "10.1016/j.ekir.2023.04.015",

language = "English",

volume = "8",

pages = "1342--1351",

journal = "Kidney International Reports",

issn = "2468-0249",

publisher = "Elsevier Inc.",

number = "7",

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TY - JOUR

T1 - Sex Differences in the Association Between Serum Testosterone and Kidney Function in the General Population

AU - van der Burgh, Anna C.

AU - Aribas, Elif

AU - Ikram, M. Arfan

AU - Kavousi, Maryam

AU - Neggers, Sebastian J.C.M.M.

AU - Hoorn, Ewout J.

AU - Chaker, Layal

N1 - Funding Information: We gratefully acknowledge the dedication, commitment, and contribution of the study participants, the staff of the Rotterdam Study, and the participating general practitioners and pharmacists. The Rotterdam Study is funded by the Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands, Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. None of the funders had any role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The datasets analyzed during the current study are not publicly available because of legal and ethical restraints. Data are available from the corresponding author on reasonable request. Conceptualization was done by ACB, EJH, and LC. Methodology was done by ACB and LC. Formal analysis and investigation were conducted by ACB. Writing-original draft preparation was done by ACB. Writing-review and editing were done by ACB, EA, MAI, MK, SN, EJH, and LC. Supervision was by EJH and LC. Publisher Copyright: © 2023 International Society of Nephrology

PY - 2023/7

Y1 - 2023/7

N2 - Introduction: Testosterone might prevent kidney function decline, although evidence is limited in men and lacking in women from the general population. We investigated the association between serum testosterone and kidney function in men and women from a large population-based cohort study. Methods: Participants aged ≥45 years with available measurements of serum testosterone, sex hormone-binding globulin (SHBG), creatinine, and cystatine C were included. Assessments of kidney function included baseline assessments of the estimated glomerular filtration rate (eGFR) based on serum creatinine (eGFRcreat) or serum cystatin C (eGFRcys), and the urine albumin-to-creatinine ratio (ACR), and repeated assessments of eGFRcreat. Linear regression and linear mixed models were used to assess the associations of serum free and total testosterone with kidney function, stratified for sex. Results: A total of 4095 men and 5389 women (mean age 65.2 years) were included. In men, higher free testosterone was associated with lower eGFRcreat (beta −0.63, 95% confidence interval [CI]: −1.05; −0.21), higher eGFRcys (beta 0.56, 95% CI: 0.07; 1.05), and lower ACR (beta −0.25, 95% CI: −0.35; −0.16) at baseline. Higher total testosterone was associated with higher baseline and follow-up eGFRcreat, and with lower eGFRcreat when additionally adjusted for SHBG. In women, higher free testosterone was associated with lower baseline eGFRcreat and eGFRcys (beta −1.03, 95% CI: −1.36; −0.71; beta −1.07, 95% CI: −1.44; −0.70; respectively) and lower eGFRcreat over time (beta −0.78, 95% CI: −1.10; −0.46), but not with ACR. Conclusions: eGFRcys might be a better parameter than eGFRcreat for the association of testosterone with kidney function, although further studies investigating this are needed. Furthermore, we identified sex differences in the association between testosterone and kidney function, with a positive association in men and a negative association in women.

AB - Introduction: Testosterone might prevent kidney function decline, although evidence is limited in men and lacking in women from the general population. We investigated the association between serum testosterone and kidney function in men and women from a large population-based cohort study. Methods: Participants aged ≥45 years with available measurements of serum testosterone, sex hormone-binding globulin (SHBG), creatinine, and cystatine C were included. Assessments of kidney function included baseline assessments of the estimated glomerular filtration rate (eGFR) based on serum creatinine (eGFRcreat) or serum cystatin C (eGFRcys), and the urine albumin-to-creatinine ratio (ACR), and repeated assessments of eGFRcreat. Linear regression and linear mixed models were used to assess the associations of serum free and total testosterone with kidney function, stratified for sex. Results: A total of 4095 men and 5389 women (mean age 65.2 years) were included. In men, higher free testosterone was associated with lower eGFRcreat (beta −0.63, 95% confidence interval [CI]: −1.05; −0.21), higher eGFRcys (beta 0.56, 95% CI: 0.07; 1.05), and lower ACR (beta −0.25, 95% CI: −0.35; −0.16) at baseline. Higher total testosterone was associated with higher baseline and follow-up eGFRcreat, and with lower eGFRcreat when additionally adjusted for SHBG. In women, higher free testosterone was associated with lower baseline eGFRcreat and eGFRcys (beta −1.03, 95% CI: −1.36; −0.71; beta −1.07, 95% CI: −1.44; −0.70; respectively) and lower eGFRcreat over time (beta −0.78, 95% CI: −1.10; −0.46), but not with ACR. Conclusions: eGFRcys might be a better parameter than eGFRcreat for the association of testosterone with kidney function, although further studies investigating this are needed. Furthermore, we identified sex differences in the association between testosterone and kidney function, with a positive association in men and a negative association in women.

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U2 - 10.1016/j.ekir.2023.04.015

DO - 10.1016/j.ekir.2023.04.015

M3 - Article

C2 - 37441475

AN - SCOPUS:85161721389

SN - 2468-0249

VL - 8

SP - 1342

EP - 1351

JO - Kidney International Reports

JF - Kidney International Reports

IS - 7

ER -

Sex Differences in the Association Between Serum Testosterone and Kidney Function in the General Population

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