Alterations in hepatic lipase and lipoprotein subfractions with transdermal testosterone replacement therapy

The effect of sex hormone replacement therapy on lipoprotein metabolism is thought to be less marked with the transdermal route because of the lack of hepatic first-pass effect. The aim of this study was to evaluate the effects of testosterone replacement therapy given transdermally via a permeation-enhanced system on plasma lipolytic enzymes (hepatic and lipoprotein lipase), LDL and HDL subfraction concentrations.

Ten patients with primary testicular failure were started on transdermal testosterone (Testoderm(R)). Plasma lipids, lipoproteins and post-heparin plasma lipolytic enzymes were evaluated before and after 3 months of treatment. LDL and HDL subfractions were measured by density gradient ultracentrifugation and hepatic and lipoprotein lipase activities by radio-enzymatic method.

Serum testosterone level increased to within the normal range in all subjects whereas serum dihydrotestosterone (DHT) increased to supra-normal values. Plasma hepatic lipase (HL) activity increased after testosterone replacement (24.7 +/- 7.5 vs. 29.2 +/- 8.3 micromol free fatty acid released per hour, P < 0.05) and the increase in HL correlated with the increase in DHT (r = 0.64, P < 0. 05). Small changes were observed in LDL subfraction pattern with an increase in the concentration of small dense LDL-III (80.1 +/- 30.3 vs. 93.0 +/- 27.8 mg/l, P < 0.05). No significant change was seen in the HDL2 subfraction but HDL3 decreased after treatment (0.93 +/- 0. 17 vs. 0.79 +/- 0.14 mmol/l, P < 0.01).

Testosterone replacement, given via a permeation-enhanced transdermal system, is associated with changes in hepatic lipase activity and in LDL and HDL subfractions. Whether these changes adversely influence the cardiovascular risk in the longterm remains to be determined.