Sociodemographic, lifestyle, and medical factors associated with calculated free testosterone concentrations in men: individual participant data meta-analyses

Nick Narinx; Ross J Marriott; Kevin Murray; Robert J Adams; Christie M Ballantyne; Douglas C Bauer; Shalender Bhasin; Mary L Biggs; Peggy M Cawthon; David J Couper; Adrian S Dobs; Leon Flicker; Graeme J Hankey; Anke Hannemann; Robin Wilkening; Sean A Martin; Alvin M Matsumoto; Claes Ohlsson; Terence W O'Neill; Eric S Orwoll; Molly M Shores; Antje Steveling; Thomas G Travison; Gary A Wittert; Frederick C W Wu; Leen Antonio; Dirk Vanderschueren; Bu B Yeap

doi:10.1093/ejendo/lvae133

Sociodemographic, lifestyle, and medical factors associated with calculated free testosterone concentrations in men: individual participant data meta-analyses

Eur J Endocrinol. 2024 Oct 29;191(5):523-534. doi: 10.1093/ejendo/lvae133.

Authors

Nick Narinx^{1

2}, Ross J Marriott³, Kevin Murray³, Robert J Adams⁴, Christie M Ballantyne⁵, Douglas C Bauer⁶, Shalender Bhasin⁷, Mary L Biggs⁸, Peggy M Cawthon⁹, David J Couper¹⁰, Adrian S Dobs¹¹, Leon Flicker^{12

13}, Graeme J Hankey^{12

14}, Anke Hannemann^{15

16}, Robin Wilkening^{17

18}, Sean A Martin¹⁹, Alvin M Matsumoto^{20

21}, Claes Ohlsson²², Terence W O'Neill²³, Eric S Orwoll²⁴, Molly M Shores²⁵, Antje Steveling²⁶, Thomas G Travison^{7

27}, Gary A Wittert²⁸, Frederick C W Wu²⁹, Leen Antonio¹, Dirk Vanderschueren^{1

2}, Bu B Yeap^{12

30}

Affiliations

¹ Laboratory of Clinical and Experimental Endocrinology, KU Leuven, 3000 Leuven, Belgium.
² Department of Laboratory Medicine, UZ Leuven, 3000 Leuven, Belgium.
³ School of Population and Global Health, University of Western Australia, Perth 6009, Australia.
⁴ Adelaide Institute for Sleep Health, Flinders University, Bedford Park, South Australia 5042, Australia.
⁵ Internal Medicine, Baylor College of Medicine, Houston, TX 77046, United States.
⁶ General Internal Medicine, University of California, San Francisco 94115, United States.
⁷ Brigham and Women's Hospital, Harvard Medical School, Boston 02115, United States.
⁸ Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA 98115, United States.
⁹ San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA 94158, United States.
¹⁰ Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, United States.
¹¹ School of Medicine, Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins University, Baltimore, MD 21287, United States.
¹² Medical School, University of Western Australia, Perth 6009, Australia.
¹³ Western Australian Centre for Health and Ageing, University of Western Australia, Perth 6000, Australia.
¹⁴ Perron Institute for Neurological and Translational Science, Perth 6009, Australia.
¹⁵ Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17489 Greifswald, Germany.
¹⁶ DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, 17475 Greifswald, Germany.
¹⁷ School of Public Health and Preventive Medicine, Monash University, Melbourne 3004, Australia.
¹⁸ European University of Applied Sciences, 18057 Rostock, Germany.
¹⁹ Australian Institute of Family Studies, Southbank 3006, Australia.
²⁰ Department of Medicine, Division of Gerontology & Geriatric Medicine, University of Washington School of Medicine, Seattle, WA 98104, United States.
²¹ Geriatric Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA 98108, United States.
²² Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, 405 30 Goteborg, Sweden.
²³ Centre for Epidemiology Versus Arthritis, University of Manchester and NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester M13 9PT, United Kingdom.
²⁴ Oregon Health and Science University, Portland, OR 97239, United States.
²⁵ School of Medicine, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98102, United States.
²⁶ Department of Internal Medicine, University Medicine Greifswald, 17475 Greifswald, Germany.
²⁷ Institute for Aging Research, Hebrew Senior Life, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02131, United States.
²⁸ Freemasons Centre for Men's Health and Wellbeing, School of Medicine, University of Adelaide, Adelaide 5000, Australia.
²⁹ Division of Endocrinology, Diabetes & Gastroenterology, School of Medical Sciences, University of Manchester, Manchester M13 9NT, United Kingdom.
³⁰ Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth 6150, Australia.

PMID: 39575586
DOI: 10.1093/ejendo/lvae133

Abstract

Objective: Sociodemographic, lifestyle, and medical variables influence total testosterone (T) and sex hormone-binding globulin (SHBG) concentrations. The relationship between these factors and "free" T remains unclear. We examined 21 sociodemographic, lifestyle, and medical predictors influencing calculated free T (cFT) in community-dwelling men across ages.

Design: This is a cross-sectional analysis in 20 631 participants in the Androgens in Men Study.

Methods: Individual participant data (IPD) were provided by 9 cohorts. Total T was determined using mass spectrometry, SHBG using immunoassays, and cFT using the Vermeulen formula. Associations were analyzed using 2-stage random effects IPD meta-analyses.

Results: Cohort median ages ranged from 40 to 76 years and median cFT concentrations from 174.3 to 422.8 pmol/L. In men aged 17-99 years, there was a linear inverse association of cFT with age (-57.2 pmol/L [95% confidence interval, -69.4, -44.9] per 1 SD increase in age). Calculated free T increased with increasing baseline body mass index (BMI) among men with BMI < 23.6 kg/m2, but decreased among men with BMI > 23.6 kg/m2 (-24.7 pmol/L [-29.1, -20.3] per 1 SD increase in the 25.4-29.6 kg/m2 BMI range). Calculated free T was lower in younger men, who were married or in a de facto relationship (-18.4 pmol/L [-27.6, -9.3]) and in men who formerly smoked (-5.7 pmol/L [-8.9, -2.6]), were in poor general health (-14.0 pmol/L [-20.1, -7.8]), and had diabetes (-19.6 pmol/L [-23.0, -16.3]), cardiovascular disease (-5.8 pmol/L [-8.3, -3.2]), or cancer (-19.2 pmol/L [-24.4, -14.1]).

Conclusions: Calculated free T was most prominently associated with age and BMI. The linear, inverse association with age, nonlinear association with BMI, and presence of diabetes, cancer, and sociodemographic factors should be considered when interpreting cFT values.

Keywords: Vermeulen formula; age; body mass index; calculated free testosterone; male.

Publication types

Meta-Analysis

MeSH terms

Adolescent
Adult
Age Factors
Aged
Aged, 80 and over
Body Mass Index
Cohort Studies
Cross-Sectional Studies
Humans
Life Style*
Male
Middle Aged
Sex Hormone-Binding Globulin* / analysis
Sex Hormone-Binding Globulin* / metabolism
Sociodemographic Factors
Socioeconomic Factors
Testosterone* / blood
Young Adult

Substances

Testosterone
Sex Hormone-Binding Globulin

Abstract

Publication types

MeSH terms

Substances

Grants and funding