The associations between androgens and cardiovascular risk factors in men are controversial. A nested case-control study was used to compare the levels of cardiovascular risk factors in two groups (n = 25 each) of healthy men contrasted by their plasma total testosterone (PTT) concentration, matched by age and ethnic origin. Compared to the men with normal PTT (mean +/- SEM, 19.8 +/- 0.7 nmol/L), the men with low PTT (10.1 +/- 0.3 nmol/L) had a significantly higher body mass index (P < 0.01), waist/hip ratio (P < 0.001), systolic blood pressure (P < 0.05), fasting and 2-h plasma glucose (P < 0.04 and P < 0.02 respectively), serum triglycerides (P < 0.001), total cholesterol (P < 0.04), low density lipoprotein cholesterol (P < 0.01), apolipoprotein B (P < 0.01), fasting and 2-h plasma insulin (both P < 0.0001), and lower values of serum high density lipoprotein cholesterol (P < 0.01) and apolipoprotein AI (P < 0.05). After adjustment for both body mass index and waist/hip ratio, fasting and 2-h plasma insulin and triglyceride levels remained significantly different between the two groups (P < 0.04, P < 0.001, and P < 0.03 respectively). Plasma sex hormone-binding globulin was markedly decreased in the low PTT group (P < 0.0001), whereas bioavailable testosterone was not significantly different. This case-control study provides further and stronger evidence of a negative association between PTT and plasma insulin in men, as suggested by cross-sectional studies. Because these are observational data, neither causality nor the direction of the associations among PTT, sex hormone-binding globulin, and insulin sensitivity can be determined. Intervention studies are needed to better assess the metabolic and cardiovascular benefits of androgen treatment that have been suggested by preliminary clinical trials.

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