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

Departments of Internal Medicine and Geriatrics (L.V., D.M., M.L., C.S., U.S., Å.T., C.O.), Gothenburg University, SE-41345 Gothenburg, Sweden; Department of Clinical Sciences (M.K.K.), Clinical and Molecular Osteoporosis Research Unit, Lund University, and Department of Orthopaedics, Malmö University Hospital, S-205 02 Malmö, Sweden; Department of Radiology (J.B.), Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden; Department of Interventional Radiology (L.L.), Rigs Hospital, 2100 Copenhagen Ø, Denmark; Bone and Mineral Unit (E.O.), Oregon Health and Sciences University, Portland, Oregon 97239; Laboratory of Molecular Endocrinology and Oncology (F.L.), Laval University Hospital Research Center and Laval University, Québec, Canada G1V 4G2; and Department of Medical Sciences (Ö.L.), University of Uppsala, SE-751 85 Uppsala, Sweden

Address all correspondence and requests for reprints to: Claes Ohlsson, M.D., Ph.D., Professor, Division of Endocrinology, Department of Internal Medicine, Sahlgrenska University Hospital, SE-41345 Göteborg, Sweden. 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-3,17ß-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-3,17ß-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.