Effects on lipoprotein particles of long-term dehydroepiandrosterone in elderly men and women and testosterone in elderly men

Context: Although age-related declines in dehydroepiandrosterone sulfate (DHEAS) and testosterone are associated with cardiovascular risk, it remains to be determined whether replacement of these hormones improves cardiovascular risk factors. Objective: This study sought to determine the effect of long-term replacement of dehydroepiandrosterone (DHEA) in elderly men and women and testosterone in elderly men on lipid and lipoprotein concentrations and particle sizes. Methods: A 2-yr randomized, placebo-controlled, double-blind study was conducted in 87 elderly men with low levels of DHEAS and bioavailable testosterone and 57 elderly women with low levels of DHEAS. Amongelderly men, 29 received DHEA (75 mg/d), 27 received testosterone (5 mg/d), and 31 received placebo. Among the elderly women, 27 received DHEA (50 mg/d), and 30 received placebo. Baseline lipoprotein profiles in the elderly were compared to healthy younger participants. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle sizes and concentrations were quantified using nuclear magnetic resonance spectroscopy. Results: The elderly had higher concentrations of total cholesterol, triglycerides, LDL cholesterol, total LDL particles, and small, dense LDL particles than the young. In men, neither DHEA nor testosterone affected LDL or HDL particle concentrations. In women, DHEA reduced HDL cholesterol [median difference (95% confidence intervals), -5.0 (-8.0, -2.0) mg/dl; P = 0.002] and the number of large HDL particles [-1.0 (-1.8, -0.2) μmol/liter; P = 0.003]. Conclusions: Long-term DHEA and testosterone had no significant effect on plasma lipoproteins in elderly men, but elderly women showed a lowering of the large HDL particles that may have potential adverse clinical implications.