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This version published online on August 21, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-0252
A more recent version of this article appeared on November 1, 2007
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Submitted on February 2, 2007
Accepted on August 13, 2007

Androgens and Glucuronidated Androgen Metabolites are Associated with Metabolic Risk Factors in Men

Liesbeth Vandenput, Dan Mellström, Mattias Lorentzon, Charlotte Swanson, Magnus K Karlsson, John Brandberg, Lars Lönn, Eric Orwoll, Ulf Smith, Fernand Labrie, Östen Ljunggren, Åsa Tivesten, and Claes Ohlsson*

Departments of Internal Medicine and Geriatrics, Gothenburg University, Gothenburg, Sweden; Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Department of Orthopaedics, Malmö University Hospital, Malmö, Sweden; Department of Radiology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Interventional Radiology, Rigs Hospital, Copenhagen, Denmark; Bone and Mineral Unit, Oregon Health and Sciences University, Portland, OR; Laboratory of Molecular Endocrinology and Oncology, Laval University Hospital Research Center (CRCHUL) and Laval University, Québec, Canada; and Department of Medical Sciences, University of Uppsala, Uppsala, Sweden

* To whom correspondence should be addressed. E-mail: Claes.Ohlsson{at}medic.gu.se.

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-3{alpha},17{beta}-diol-17glucuronide (17G) was independently positively associated with fat mass (P<0.001). Most importantly, the 17G/DHT ratio was strongly correlated, not only with fat mass, but also with central fat distribution, intra-hepatic 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 HOMA index (10%) and HDL cholesterol (7%).

Conclusion: Our findings demonstrate that 17-glucuronidation of the DHT metabolite androstane-3{alpha},17{beta}-diol is strongly associated with several metabolic risk factors in men. Future longitudinal studies are required to determine the possible impact of the 17G/DHT ratio as a metabolic risk factor in men.
Key words: androgens • glucuronidated androgen metabolites • metabolic risk factors • population studies • men






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