TY - JOUR
T1 - Androgens and glucuronidated androgen metabolites are associated with metabolic risk factors in men
AU - Vandenput, Liesbeth
AU - Mellström, Dan
AU - Lorentzon, Mattias
AU - Swanson, Charlotte
AU - Karlsson, Magnus K.
AU - Brandberg, John
AU - Lönn, Lars
AU - Orwoll, Eric
AU - Smith, Ulf
AU - Labrie, Fernand
AU - Ljunggren, Östen
AU - Tivesten, Åsa
AU - Ohlsson, Claes
N1 - Funding Information:
This work was supported by the Swedish Research Council, the Swedish Foundation for Strategic Research, the Läkarutbildningsavtal grant from the Sahlgrenska University Hospital, the Lundberg Foundation, the Torsten and Ragnar Söderberg’s Foundation, Petrus and Augusta Hedlunds Foundation, Endorecherche, and the Novo Nordisk Foundation.
PY - 2007/11
Y1 - 2007/11
N2 - Context: Androgens are associated with metabolic risk factors in men. However, the independent impact of androgens and androgen metabolites on metabolic risk factors in men is unclear. Objective: Our objective was to determine the predictive value of serum levels of androgens and glucuronidated androgen metabolites for metabolic risk factors. Design and Study Subjects: We conducted a population-based study of two Swedish cohorts (1068 young adult and 1001 elderly men). Main Outcome Measures: We measured correlation of serum dihydrotestosterone (DHT), testosterone (T), and glucuronidated androgen metabolites with fat mass, fat distribution, serum lipids, and insulin resistance. Results: Both DHT and T were negatively associated with different measures of fat mass in both cohorts (P < 0.001). Further statistical analysis indicated that DHT, but not T, was independently negatively associated with different measures of fat mass and insulin resistance (P < 0.001). The glucuronidated androgen metabolite androstane-3α,17β-diol- 17glucuronide (17G) was independently positively associated with fat mass (P < 0.001). Most importantly, the 17G to DHT ratio was strongly correlated, not only with fat mass but also with central fat distribution, intrahepatic fat, disturbed lipid profile, insulin resistance, and diabetes, explaining a substantial part of the total variance in total body fat (12% in young adult men, 15% in elderly men), the homeostasis model assessment index (10%), and high-density lipoprotein cholesterol (7%). Conclusion: Our findings demonstrate that 17-glucuronidation of the DHT metabolite androstane-3α,17β-diol is strongly associated with several metabolic risk factors in men. Future longitudinal studies are required to determine the possible impact of the 17G to DHT ratio as a metabolic risk factor in men.
AB - Context: Androgens are associated with metabolic risk factors in men. However, the independent impact of androgens and androgen metabolites on metabolic risk factors in men is unclear. Objective: Our objective was to determine the predictive value of serum levels of androgens and glucuronidated androgen metabolites for metabolic risk factors. Design and Study Subjects: We conducted a population-based study of two Swedish cohorts (1068 young adult and 1001 elderly men). Main Outcome Measures: We measured correlation of serum dihydrotestosterone (DHT), testosterone (T), and glucuronidated androgen metabolites with fat mass, fat distribution, serum lipids, and insulin resistance. Results: Both DHT and T were negatively associated with different measures of fat mass in both cohorts (P < 0.001). Further statistical analysis indicated that DHT, but not T, was independently negatively associated with different measures of fat mass and insulin resistance (P < 0.001). The glucuronidated androgen metabolite androstane-3α,17β-diol- 17glucuronide (17G) was independently positively associated with fat mass (P < 0.001). Most importantly, the 17G to DHT ratio was strongly correlated, not only with fat mass but also with central fat distribution, intrahepatic fat, disturbed lipid profile, insulin resistance, and diabetes, explaining a substantial part of the total variance in total body fat (12% in young adult men, 15% in elderly men), the homeostasis model assessment index (10%), and high-density lipoprotein cholesterol (7%). Conclusion: Our findings demonstrate that 17-glucuronidation of the DHT metabolite androstane-3α,17β-diol is strongly associated with several metabolic risk factors in men. Future longitudinal studies are required to determine the possible impact of the 17G to DHT ratio as a metabolic risk factor in men.
UR - http://www.scopus.com/inward/record.url?scp=35948983720&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=35948983720&partnerID=8YFLogxK
U2 - 10.1210/jc.2007-0252
DO - 10.1210/jc.2007-0252
M3 - Article
C2 - 17711928
AN - SCOPUS:35948983720
SN - 0021-972X
VL - 92
SP - 4130
EP - 4137
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 11
ER -