Intra-abdominal adipose tissue is independently associated with sex-hormone binding globulin in premenopausal women
Open accessAbstract
Lower serum concentrations of sex‐hormone binding globulin (SHBG) are associated with increased risk for several obesity‐related diseases in women including hormone‐sensitive cancers, type 2 diabetes, metabolic syndrome, and cardiovascular disease. Previous investigations have reported that body composition, specifically central obesity, and/or higher insulin concentrations are key factors associated with lower SHBG in overweight and obese women; however, these studies were limited by their cross‐sectional design. We hypothesized that intra‐abdominal adipose tissue (IAAT), a fat depot linked with an abnormal metabolic profile, is inversely and independently associated with SHBG. Therefore, we determined the longitudinal associations among SHBG, insulin, and IAAT in 107 premenopausal women enrolled in a weight loss study. Overweight (BMI 27–30 kg/m 2) women were weight reduced until BMI of ≤24 was achieved. Body composition and IAAT were measured at baseline and after weight loss with dual‐energy X‐ray absorptiometry and computed tomography, respectively. Serum concentrations of insulin and SHBG were determined. Paired t‐test showed that insulin and IAAT decreased significantly and SHBG increased significantly following weight loss (P < 0.0001 for all). Simple correlations from baseline showed no association with insulin and SHBG (r = −0.142, P = 0.143) and a significant inverse association between IAAT and SHBG (r = −0.43, P < 0.0001). Repeated measures mixed‐model showed that after adjusting for age and time (weight loss), IAAT was significantly inversely associated with SHBG (P = 0.0002) and there was no association with insulin and SHBG (P = 0.180). We conclude that SHBG concentrations are influenced by IAAT and not insulin in premenopausal women.
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Visceral fat may actively suppress SHBG synthesis, potentially through inflammatory pathways or hepatic fat accumulation.
“suggesting that visceral fat may actively suppress SHBG synthesis, potentially through inflammatory pathways or hepatic fat accumulation (111, 117).”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [111]
The Discussion (page unavailable) suggests that intra-abdominal fat may reduce SHBG production through hepatic metabolism and considers free fatty acids and hepatic fat accumulation as possible links. It does not identify an inflammatory pathway, and says the mechanism remains unclear; the study did not measure hepatic fat. (LLM, conf=0.87)
Experimental — accuracy not yet measuredSHBG levels are inversely correlated with markers of adiposity including BMI and waist-to-hip ratio.
“SHBG levels are inversely correlated with markers of adiposity that include BMI and WHR (111, 112).”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [111]
The Results (page unavailable) report inverse correlations between SHBG and total fat mass and intra-abdominal adipose tissue, supporting the broader adiposity association. BMI was examined but was not among the significant baseline correlations reported, and waist-to-hip ratio was not measured in this study; the Introduction mentions it only as an indicator used in earlier studies. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSeveral cross-sectional studies have shown an inverse relationship between SHBG and intra-abdominal adipose tissue.
“Several cross-sectional studies have shown an inverse relationship between SHBG and IAAT”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [111]
The Introduction (page not provided) identifies one prior cross-sectional study linking IAAT and SHBG. The Results also report an inverse correlation at baseline in this paper’s longitudinal study. The copy does not establish that several cross-sectional studies found this specific relationship. (LLM, conf=0.86)
Experimental — accuracy not yet measuredLow SHBG levels predict type 2 diabetes and metabolic syndrome incidence, even after adjusting for adiposity.
“low SHBG levels predict T2D and metabolic syndrome incidence, even after adjusting for adiposity (111).”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [111]
The Abstract and Introduction state that lower SHBG is associated with increased risk of both type 2 diabetes and metabolic syndrome. They do not say that SHBG predicts the incidence of either condition after adjustment for adiposity. The Methods describe adjustment in analyses of SHBG and intra-abdominal fat, not analyses of disease incidence; page numbers are unavailable in our copy. (LLM, conf=0.87)
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References 26 · Cited by 33
- Authors
- Azrad, M., Gower, B. A., Hunter, G. R., & Nagy, T. R.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Nagy, Tim R.
- Venue
- Obesity
- Publisher
- Wiley
- Published
- 2012-05
- Volume
- 20
- Issue
- 5
- Pages
- 1012-1015
- ISSN
- 1930-7381 (ISSN-L)
- 1930-739X
- PMC
- PMC3626111
- OpenAlex
- W2009641375
- Cited by
- 33
- References
- 26
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 2 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 3 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 1 · 2012: 2
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Obesity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5ul1rr025777-04, 5p60dk079626-05, UL1TR000165)
- National Cancer Institute (R25CA047888)
- National Institute of Diabetes and Digestive and Kidney Diseases (P60-DK-079626, R01DK049779, P30DK056336)
- National Center for Research Resources (UL1-RR-025777)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- sex hormone-binding globulin, intra-abdominal adipose tissue, premenopausal women, insulin, weight loss, body composition, abdominal obesity
- MeSH terms
- Adult, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Female, Humans, Longitudinal Studies, Obesity, Risk Factors, Sex Hormone-Binding Globulin, Biomarkers, Absorptiometry, Photon, Body Mass Index, Premenopause, Metabolic Syndrome, Intra-Abdominal Fat
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