EFFECTS OF TESTOSTERONE REPLACEMENT ON HDL SUBFRACTIONS AND APOLIPOPROTEIN-A-I CONTAINING LIPOPROTEINS

OBJECTIVES Gonadal steroids are important regulators of lipoprotein me tabolism, The aims of this study were to determine the effects of a mi nimum effective dose of testosterone replacement on high density lipop rotein (HDL) subfractions and apolipoprotein (ape) A-I containing part icles (lipoprotein (Lp)A-I) and LpA-I:A-II) in hypogonadal men with pr imary testicular failure and to investigate the underlying mechanisms of these changes, MEASUREMENTS Eleven Chinese hypogonadal men were sta rted on testosterone enanthate 250 mg intramuscularly at 4-weekly inte rvals. HDL was subfractionated by density gradient ultracentrifugation and LpA-I was analysed by electro-immunodiffusion after 3, 6 and 12 w eeks of treatment. Plasma cholesteryl ester transfer protein (CETP) ac tivity and lipolytic enzymes activities in post-heparin plasma were me asured to determine the mechanisms underlying testosterone-induced cha nges in HDL. RESULTS The dosage of testosterone enanthate used in the present study resulted in suboptimal trough testosterone levels. No ch anges were seen in plasma total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C,) apo a and apo(a) after 12 weeks. The re was a drop in HDL3-C compared to baseline (0.82 +/- 0.17 mmol/l vs, 0.93 +/- 0.13, P < 0.01) whereas a small but significant increase was seen in HDL2-C (0.21 +/- 0.13 mmol/l vs. 0.11 +/- 0.09, P < 0.05). Pl asma apo A-I decreased after treatment (1.34 +/- 0.25 particles (0.86 +/- 0.18 g/l vs. 0.99 +/- 0.24, P < 0.01). No changes were observed in the levels of LpA-I particles. No significant changes were seen in pl asma CETP and lipoprotein lipase activities after testosterone replace ment but there was a transient increase in hepatic lipase (HL) activit y at weeks 3 and 6. The decrease in HDL correlated with the increase i n HL activity (r = 0.62, P < 0.05). CONCLUSIONS Testosterone replaceme nt in the form of parenteral testosterone ester given 4-weekly, althou gh unphysiological, was not associated with unfavourable changes in li pid profiles, The reduction in HDL was mainly in HDL3-C and in LpA-I:A -II particles and not in the more anti-atherogenic HDL2 and LpA-I part icles. The changes in HDL subclasses were mainly mediated through the effect of testosterone on hepatic lipase activity.