Walsh B W, Sacks F M
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
J Clin Invest. 1993 May;91(5):2126-32. doi: 10.1172/JCI116437.
Oral contraceptives (OC) raise plasma triglyceride and VLDL levels, which may be of concern, since some conditions characterized by elevated triglycerides are associated with atherosclerosis. To identify the responsible mechanism, we studied 11 healthy premenopausal women, 5 of whom were taking OC containing 0.035 mg ethinyl estradiol, and 6 of whom were not. Their rates of VLDL and LDL metabolism were measured by endogenously labeling apoB, the protein component of VLDL and LDL, by an intravenous infusion of deuterated leucine. OC use had the greatest effect on the large, triglyceride-rich VLDL subfraction (Sf 60-400), increasing plasma levels threefold and production rates fivefold (P < 0.05). Among OC users, small VLDL (Sf 20-60) levels were 2.2 times higher, and production rates were 3.4-fold higher (P < 0.05). The fractional catabolic rates of large and small VLDL were similar among OC users and nonusers. LDL levels and metabolic rates were not significantly different between the two groups. Thus, contemporary low dose OC substantially raise VLDL levels by increasing the production rate of large, triglyceride-rich VLDL, and not by slowing VLDL catabolism. Since VLDL catabolism is not impaired, we speculate that the hypertriglyceridemia induced by OC may be less atherogenic than that of hypertriglyceridemia resulting from impaired lipolysis. This may explain why long-term OC use does not appear to promote atherosclerosis.
口服避孕药(OC)会升高血浆甘油三酯和极低密度脂蛋白(VLDL)水平,这可能令人担忧,因为一些以甘油三酯升高为特征的病症与动脉粥样硬化有关。为了确定其作用机制,我们研究了11名健康的绝经前女性,其中5名正在服用含0.035毫克炔雌醇的口服避孕药,另外6名未服用。通过静脉输注氘代亮氨酸对内源性标记载脂蛋白B(VLDL和LDL的蛋白质成分)来测量她们的VLDL和LDL代谢率。使用口服避孕药对富含甘油三酯的大颗粒VLDL亚组分(Sf 60 - 400)影响最大,使血浆水平增加了三倍,生成率增加了五倍(P < 0.05)。在口服避孕药使用者中,小颗粒VLDL(Sf 20 - 60)水平高2.2倍,生成率高3.4倍(P < 0.05)。口服避孕药使用者和非使用者中,大颗粒和小颗粒VLDL的分解代谢率相似。两组之间LDL水平和代谢率无显著差异。因此,当代低剂量口服避孕药通过增加富含甘油三酯的大颗粒VLDL的生成率而非减缓VLDL分解代谢来大幅提高VLDL水平。由于VLDL分解代谢未受损,我们推测口服避孕药诱导的高甘油三酯血症可能比因脂解受损导致的高甘油三酯血症的动脉粥样硬化风险更低。这可能解释了为什么长期使用口服避孕药似乎不会促进动脉粥样硬化。