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

OBJECTIVES The effect of sex hormone replacement therapy on lipoprotein met abolism 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 evaluat e the effects of testosterone replacement therapy given transdermally via a permeation-enhanced system on plasma lipolytic enzymes (hepatic and lipopr otein lipase), LDL and HDL subfraction concentrations. MEASUREMENTS Ten patients with primary testicular failure were started on t ransdermal testosterone (Testoderm(R)). Plasma lipids, lipoproteins and pos theparin plasma lipolytic enzymes were evaluated before and after 3 months of treatment, LDL and HDL subfractions were measured by density gradient ul tracentrifugation and hepatic and lipoprotein lipase activities by radio-en zymatic method. RESULTS Serum testosterone level increased to within the normal range in al l subjects whereas serum dihydrotestosterone (DHT) increased to supra-norma l values, Plasma hepatic lipase (HL) activity increased after testosterone replacement (24.7 +/- 7.5 vs. 29.2 +/- 8.3 mu mol free fatty acid released per hour, P <0.05) and the increase in HL correlated with the increase in D HT (r = 0.64, P <0.05). Small changes were observed in LDL subfraction patt ern 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 th e HDL, subfraction but HDL, decreased after treatment (0.93 +/- 0.17 vs, 0. 79 +/- 0.14 mmol/l, P <0.01). CONCLUSIONS Testosterone replacement, given via a permeation-enhanced trans dermal system, is associated with changes in hepatic lipase activity and in LDL and HDL subfractions. Whether these changes adversely influence the ca rdiovascular risk in the longterm remains to be determined.