Low levels of sex hormone-binding globulin and testosterone are associated with smaller, denser low density lipoprotein in normoglycemic men

Recently, the phenotype with a preponderance of small, dense low density lipoprotein (LDL) has been associated with increased coronary heart disease. Although previous data indicated that decreased sex hormone-binding globulin (SHBG) and testosterone concentrations are associated with increased triglyceride and decreased high density lipoprotein (HDL) cholesterol levels in men, no data are available on the relationship of LDL composition to sex hormones. Therefore, we examined the relationship of SHBG, total and free testosterone, estradiol, and dehydroepiandrosterone sulfate to LDL size (air determined by gradient gel electrophoresis) in 87 normoglycemic men. LDL size was significantly positively related to SHBG (r = 0.354) and total testosterone (r = 0.313) and inversely related to dehydroepiandrosterone sulfate (r = -0.247), but not to free testosterone or estradiol concentrations. After adjustment for age, waist circumference, overall glucose disposal, fasting glucose, triglyceride, and HDL cholesterol, LDL size remained significantly associated with SHBG (r = 0.312) and total testosterone (r = 0.269). The relationship between LDL size and total testosterone and SHBG tended to be stronger in nonobese subjects. We conclude that SHBG and total testosterone concentrations are significantly associated with LDL size in men, and these relationships appear to be independent of known confounding variables, such as triglyceride and HDL cholesterol levels. Our data suggest that endogenous sex hormones may have an independent modifying effect on LDL composition in men.