AIMTo study the relationship between circulating androgens (total testosterone [TT], free testosterone [fT] and dihydrotestosterone [DHT]) and high-density lipoprotein cholesterol (HDL-C) in men with and without cardiovascular disease (CVD).

METHODSCross-sectional analyses included 1 661 baseline samples from the Massachusetts Male Aging Study (MMAS), a population-based cohort of men ages 40-70 years. Serum hormones were measured by radioimmunoassay and HDL-C was determined following precipitation of the lower density lipoproteins. CVD was determined by self-report. Analyses were performed using multiple linear regression.

RESULTSTT and HDL-C were positively correlated in the entire sample (r=0.11, P=0.0001). After adjusting for confounders, we found this relationship was mostly limited to the 209 men with CVD. Among men with CVD, TT (P=0.0004), fT (P=0.0172) and DHT (P=0.0128) were all positively correlated with HDL-C, whereas in men without CVD only TT correlated with HDL-C (P=0.0099).

CONCLUSIONOur results suggest that if androgens contribute to CVD in middle-aged men, the effect is not related to a suppressive effect of endogenous T on HDL-C.

Adult ; Aged ; Cardiovascular Diseases ; blood ; Cholesterol, HDL ; blood ; Cross-Sectional Studies ; Humans ; Male ; Middle Aged ; Testosterone ; blood

Androgen deprivation in men leads to increased adiposity, but the mechanisms underlying androgen regulation of fat mass have not been fully defined. Androgen receptor (AR) is expressed in monocytes/macrophages, which are resident in key metabolic tissues and influence energy metabolism in surrounding cells. Male mice bearing a cell-specific knockout of the AR in monocytes/macrophages (M-ARKO) were generated to determine whether selective loss of androgen signaling in these cells would lead to altered body composition. Wild-type (WT) and M-ARKO mice (12-22 weeks of age, n = 12 per group) were maintained on a regular chow diet for 8 weeks and then switched to a high-fat diet for 8 additional weeks. At baseline and on both the regular chow and high-fat diets, no differences in lean mass or fat mass were observed between groups. Consistent with the absence of differential body weight or adiposity, no differences in food intake (3.0 ± 0.5 g per day for WT mice vs 2.8 ± 0.4 g per day for M-ARKO mice) or total energy expenditure (0.6 ± 0.1 Kcal h^-1 for WT mice vs 0.5 ± 0.1 Kcal h^-1 for M-ARKO mice) were evident between groups during high-fat feeding. Liver weight was greater in M-ARKO than that in WT mice (1.5 ± 0.1 g vs 1.3 ± 0.0 g, respectively, P = 0.02). Finally, M-ARKO mice did not exhibit impairments in glucose tolerance or insulin sensitivity relative to WT mice at any study time point. In aggregate, these findings suggest that AR signaling specifically in monocytes/macrophages does not contribute to the regulation of systemic energy balance, adiposity, or insulin sensitivity in male mice.
Adiposity/genetics* ; Animals ; Blood Glucose/metabolism* ; Energy Metabolism/genetics* ; Glucose Tolerance Test ; Homeostasis/genetics* ; Liver/anatomy & histology* ; Macrophages/metabolism* ; Male ; Mice ; Mice, Knockout ; Monocytes/metabolism* ; Organ Size ; Receptors, Androgen/metabolism* ; Signal Transduction