Visceral and Subcutaneous Adipose Tissue Assessed by Magnetic Resonance Imaging in Relation to Circulating Androgens, SHBG, and LH in Young Men

Torben Leo Nielsen, Claus Hagen, Kristian Wraae, Kim Brixen, Per Hyltoft Petersen, Egil Haug, Rasmus Larsen, Marianne Andersen

AbstractContext: No large studies have examined the relation between circulating androgen levels and regional, abdominal adiposity in young men using magnetic resonance imaging (MRI).
Objective: To study the role of visceral and subcutaneous adipose tissue (VAT and SAT) on circulating androgens and to examine the impact of obesity on androgen reference-intervals. Design, Setting, and Participants: Population-based study of 783 Danish, 20-29 year-old men. Ninety-eight men were ruled out of the healthy reference-population by predefined criteria related with hypogonadism. Total, central, and lower extremity fat mass (TFM, CFM, and LEFM) were assessed in all men by DXA and MRI was performed in 406 men. Main Outcome Measures: Total, bioavailable, and free testosterone (TT, BT, and FT), androstenedione (&#8710;4AD), dihydrotestosterone (DHT), estradiol (E2), 2/TT-ratio, sex hormone-binding globulin (SHBG), and luteinizing hormone (LH). Results: Significant, inverse, linear relationships were observed between TT, BT, FT, DHT, SHBG and all DXA measures, whereas a positive correlation was found for the E2/TT-ratio. No associations were found for &#8710;4AD. Independent, inverse relations between CFM and TT (p<10-9), BT (p<0.005), FT (p<0.005), DHT (p<0.05), and SHBG (p<10-18) as well as a positive relation between CFM and E2/TT (p<0.001) were found in multiple regression analyses. LEFM was positively associated with SHBG (p<0.005). No other outcomes were independently related with LEFM. Multiple regression analyses of the MRI data showed that VAT was independently, inversely related with BT (p=0.002) and FT (p=0.003), whereas SAT was not. SHBG was independently, inversely related to SAT (p<10-6). Both VAT and SAT were inversely associated with TT (p=0.001 and p=0.005) and DHT (p=0.024 and p=0.018), but only VAT remained significantly related with TT (p=0.003) and DHT (p=0.049) when adjusted for SHBG. LH increased with increased VAT (p=0.004), but dropped suddenly in the most viscerally obese (p=0.006). The reference-intervals for TT (8.5-29.3 vs. 12.5-37.6 nmol/l), BT (6.1-16.9 vs. 7.6-20.7 nmol/l), and DHT (0.63-2.5 vs. 0.85-3.2 nmol/l) were significantly displaced in obese men compared to non-obese men. 22.9% of the obese men and 15.3% of the ruled out men had TT levels below 12.5 nmol/l.
Conclusion: BT and FT decline linearly with increasing VAT in young men. TT and DHT are inversely related with both VAT and SAT, but the relation with SAT may be secondary to decreased SHBG levels. CFM assessed by DXA is not a useful measure of visceral adipose tissue. LH data suggest that Leydig cell function is reduced in moderate visceral obesity, while excessive visceral obesity may resemble a state of hypogonadotropic hypogonadism. The reference-intervals for TT, BT, FT, and DHT were displaced in obese men. Referenceintervals for these androgens should be established in healthy, non-obese men.
Trial Registration: ClinicalTrials.gov: NCT00150163
TypeJournal paper [With referee]
JournalJournal of Clinical Endocrinology and Metabolism
Year2007    Month April
Electronic version(s)[pdf]
BibTeX data [bibtex]
IMM Group(s)Image Analysis & Computer Graphics