Androgens and glucuronidated androgen metabolites are associated with metabolic risk factors in men.
BACKGROUND
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.


METHODS
We conducted a population-based study of two Swedish cohorts (1,068 young adult and 1,001 elderly men).


METHODS
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-3alpha,17beta-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%).


CONCLUSIONS
Our findings demonstrate that 17-glucuronidation of the DHT metabolite androstane-3alpha,17beta-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.
Vandenput
Liesbeth
L
Department of Internal Medicine, Gothenburg University, SE-41345 Gothenburg, Sweden.
Mellström
Dan
D
Lorentzon
Mattias
M
Swanson
Charlotte
C
Karlsson
Magnus K
MK
Brandberg
John
J
Lönn
Lars
L
Orwoll
Eric
E
Smith
Ulf
U
Labrie
Fernand
F
Ljunggren
Osten
O
Tivesten
Asa
A
Ohlsson
Claes
C
D000005:Abdomen / Q000033:anatomy & histology; D015502:Absorptiometry, Photon; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology; D000728:Androgens / Q000097:blood*; D001132:Arm / Q000033:anatomy & histology; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D001835:Body Weight; D015331:Cohort Studies; D005965:Glucuronates / Q000097:blood; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D007866:Leg / Q000033:anatomy & histology; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013548:Sweden; D014057:Tomography, X-Ray Computed
D000728:Androgens; D001786:Blood Glucose; D005965:Glucuronates; D012739:Gonadal Steroid Hormones; D007328:Insulin; D020738:Leptin; D008055:Lipids