Bioactive androgens and glucuronidated androgen metabolites are associated with subcutaneous and ectopic skeletal muscle adiposity among older black men

Abstract Aging is associated with declining serum levels of androgenic hormones and with increased skeletal muscle fat infiltration, an emerging risk factor for type 2 diabetes mellitus (T2DM). Androgens regulate fat mass and glucose homeostasis, but the effect of androgenic hormones on skeletal muscle fat infiltration is largely unknown. Thus, the aim of the current study was to examine the association of serum androgens and their precursors and metabolites with skeletal muscle fat infiltration and T2DM in a black male population group at high risk of T2DM. Serum androgens, estrogens, and androgen precursors and metabolites were measured using mass spectrometry; and calf skeletal muscle fat distribution (subcutaneous and intermuscular fat; skeletal muscle density) was measured using quantitative computed tomography in 472 Afro-Caribbean men 65 years and older. Bioactive androgens, testosterone, free testosterone, and dihydrotestosterone were associated with less skeletal muscle fat infiltration ( r = −0.14 to −0.18, P < .05) and increased skeletal muscle density ( r = 0.10 to 0.14, P < .05), independent of total adiposity. In addition, glucuronidated androgen metabolites were associated with less subcutaneous fat ( r = −0.11 to −0.15, P < .05). Multivariate logistic regression analysis identified an increased level of 3 α -diol-3 glucuronide (odds ratio = 1.38, P < .01) and a decreased level of dihydrotestosterone (odds ratio = 0.66, P < .01) to be significantly associated with T2DM. Our findings suggest that, in elderly black men, independent of total adiposity, bioactive androgens and glucuronidated androgen metabolites may play previously unrecognized role in skeletal muscle fat distribution. Longitudinal studies are needed to further evaluate the relationship between androgens and androgen metabolites with changes in skeletal muscle fat distribution with aging and the incidence of T2DM.