Tan K C, Shiu S W, Kung A W
Department of Medicine, University of Hong Kong, Hong Kong.
Clin Endocrinol (Oxf). 1999 Dec;51(6):765-9. doi: 10.1046/j.1365-2265.1999.00882.x.
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.
由于缺乏肝脏首过效应，人们认为经皮途径的性激素替代疗法对脂蛋白代谢的影响不太显著。本研究的目的是评估通过渗透增强系统经皮给予睾酮替代疗法对血浆脂解酶（肝脂酶和脂蛋白脂酶）、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）亚组分浓度的影响。
10例原发性睾丸功能衰竭患者开始接受经皮睾酮（Testoderm®）治疗。在治疗3个月前后评估血浆脂质、脂蛋白和肝素后血浆脂解酶。通过密度梯度超速离心法测量LDL和HDL亚组分，通过放射酶法测量肝脂酶和脂蛋白脂酶活性。
所有受试者的血清睾酮水平均升至正常范围内，而血清双氢睾酮（DHT）升至超正常水平。睾酮替代治疗后血浆肝脂酶（HL）活性增加（每小时释放的游离脂肪酸为24.7±7.5对29.2±8.3微摩尔，P<0.05），HL的增加与DHT的增加相关（r = 0.64，P<0.05）。LDL亚组分模式有微小变化，小而密的LDL-III浓度增加（80.1±30.3对93.0±27.8毫克/升，P<0.05）。HDL2亚组分无显著变化，但治疗后HDL3降低（0.93±0.17对0.79±0.14毫摩尔/升，P<0.01）。
通过渗透增强经皮系统给予睾酮替代疗法与肝脂酶活性以及LDL和HDL亚组分的变化有关。这些变化是否会长期对心血管风险产生不利影响仍有待确定。
