Suppression of Endogenous Testosterone in Young Men Increases Serum Levels of High Density Lipoprotein Subclass Lipoprotein A-I and Lipoprotein(a)1

We investigated the effect of testosterone suppression on lipoprotein metabolism in men. After a baseline period of 14 days, 12 healthy young men received over a period of 3 weeks daily s.c. injections of Cetrorelix, an antagonist of GnRH. The volunteers were then followed-up for 10 additional weeks. Administration of Cetrorelix suppressed testosterone significantly up to day 35, after which values returned to baseline. Suppression of testosterone was associated with significant and consistent increases in mean serum levels of high density lipoprotein (HDL) cholesterol by 20% (P < 0.0001), apolipoprotein A-I (apoA-I) by 10% (P = 0.0032), apoA-II by 7% (P = 0.0112), HDL subclass lipoprotein A-I (LpA-I) by 23% (P = 0.002), and plasma lecithin:cholesterol acyltransferase by 7% (P < 0.001). Serum levels of HDL subclass LpA-I/LpA-II changed insignificantly. Moreover, suppression of testosterone significantly increased the median of lipoprotein(a) [Lp(a)] levels from 5.5 to 8.5 mg/dL (P < 0.0001). The increase in Lp(a) levels was positively correlated with baseline levels of Lp(a) (r = 0.91; P < 0.001) and amounted to 40-60% in individuals with baseline levels of Lp(a) higher than 3 mg/dL. We conclude that endogenous testosterone is involved in the regulation of HDL cholesterol and Lp(a) levels and may thereby influence cardiovascular risk.