The association of obesity with sex hormone‐binding globulin is stronger than the association with ageing – implications for the interpretation of total testosterone measurements
Open accessAbstract
Summary: Objective: Total testosterone concentrations are influenced by sex hormone‐binding globulin ( SHBG ) concentrations, which are decreased by obesity and increased with ageing. Therefore, we sought to understand and compare the associations of ageing and obesity with SHBG . Design: We performed a retrospective, cross‐sectional analysis of the associations of obesity and age on SHBG and testosterone measurements in men being evaluated for hypogonadism. Patients, Measurements and Analysis: A total of 3671 men who underwent laboratory testing for testosterone deficiency from the Veterans Administration Puget Sound Health Care System from 1997 through 2007 was included. Univariate and multivariate linear regression modelling of the associations between age and body mass index ( BMI ) and SHBG was performed. Results: Obesity was associated with a significantly lower SHBG [β = −1·26 (95% CI −1·14, −1·38) nmol/l] per unit increase in BMI . In contrast, ageing was associated with a significantly increased SHBG [β = 0·46 (95% CI 0·39, 0·53) nmol/l per year] ( P < 0·001 for both effects). The association of obesity with lower SHBG was two to three times larger than the association of ageing with increased SHBG in both univariate and multivariate modelling. On average, obese men ( BMI >30 kg/m 2 ) had significantly lower SHBG and total testosterone concentrations than nonobese men [(mean ± SD ) SHBG : 36 ± 22 vs 50 ± 27 nmol/l and total testosterone: 10·5 ± 5·4 nmol/l vs 14·1 ± 7·4 nmol/l; ( P < 0·001 for both comparisons)], but calculated free testosterone concentrations did not differ between obese and nonobese men. Conclusions: We found that the association between obesity and lowered SHBG is greater than the association of ageing with increased SHBG . These competing effects may impact total testosterone measurements for the diagnosis of low testosterone, particularly in obese men.
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Male and female subjects suffering from obesity show lower levels of SHBG compared to their non-obese peers.
“Indeed, male and female subjects suffering from obesity show lower levels of SHBG compared to their non-obese peers [87, 89].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [87]
The Results report significantly lower SHBG in obese men than in nonobese men (36 ± 22 vs 50 ± 27 nmol/l). The study examined men; these passages do not support the claim about women. No page numbers were supplied. (LLM, conf=0.90)
Experimental — accuracy not yet measuredSHBG is a linking entity and can partly explain the relationship between calculated free T and metabolic parameters.
“Inversely related to and impacted by BMI, SHBG is a linking entity and can partly explain the relationship between calculated free T and these metabolic parameters [87].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [87]
The Results report an inverse association between BMI and SHBG, and the Methods state that SHBG was used to calculate free testosterone. The Discussion also notes associations between low SHBG and metabolic syndrome. However, the paper does not show that SHBG explains a relationship between calculated free testosterone and metabolic parameters; calculated free testosterone did not differ between obese and nonobese men. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe relationship between plasma SHBG levels and obesity is stronger than the positive association of SHBG with age; SHBG concentrations are highest in non-obese older men and lowest in obese younger men.
“Furthermore, this relationship between plasma SHBG levels and obesity is stronger than the positive association of SHBG with age described earlier. SHBG concentrations are highest in non-obese older men and lowest in obese younger men [87].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [87]
A consistent finding is the negative association between SHBG and BMI.
“A consistent finding is the negative association between SHBG and BMI [86, 87].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [87]
Modest obesity is predominantly associated with reduced total testosterone due to insulin resistance associated reductions in SHBG.
“Modest obesity is predominantly associated with reduced total testosterone due to insulin resistance associated reductions in its carrier protein sex hormone binding globulin (SHBG). 64 , 65”
From The role of the androgen receptor in the pathogenesis of obesity and its utility as a target for obesity treatments (2022) · cites this paper as [64]
Obesity has been reported to be associated with lower circulating levels of SHBG.
“Obesity has been reported to be associated with lower circulating levels of SHBG.”
From The role of the androgen receptor in the pathogenesis of obesity and its utility as a target for obesity treatments (2022) · cites this paper as [64]
SHBG is inversely associated in men with obesity.
“SHBG is inversely associated in men with obesity, 64 , 218”
From The role of the androgen receptor in the pathogenesis of obesity and its utility as a target for obesity treatments (2022) · cites this paper as [64]
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- Authors
- Cooper, L. A., Page, S. T., Amory, J. K., Anawalt, B. D., & Matsumoto, A. M.
- Affiliations
- University of Washington (US)
- Corresponding author
- Anawalt, Bradley D.
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2015-05-11
- Volume
- 83
- Issue
- 6
- Pages
- 828-833
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- PMC
- PMC4782930
- OpenAlex
- W2169467998
- Cited by
- 117
- References
- 33
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 13 · 2023: 12 · 2022: 12 · 2021: 15 · 2020: 13 · 2019: 5 · 2018: 7 · 2017: 2 · 2016: 8 · 2015: 2
- FWCI
- 5.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (T32HL0007028, AG037603A)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- sex hormone-binding globulin, obesity, aging, total testosterone, free testosterone, hypogonadism, androgen deficiency, body mass index, men
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Cross-Sectional Studies, Humans, Male, Middle Aged, Obesity, Retrospective Studies, Sex Hormone-Binding Globulin, Testosterone, Body Mass Index, Young Adult
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