Recent observations suggest that the risk of coronary artery disease (CAD) is associated with both the level and composition of the two major populations of apolipoprotein (apo)-defined high-density lipoprotein (HDL) particles: those containing both apo A-I and apo A-II [Lp(AI,AII)] and those containing apo A-I without apo A-II [Lp(AI)]. While sex hormones are known to affect HDL, their influence on these apo-defined HDL particles is not known. We have determined the effects of two triphasic oral contraceptive (OC) formulations on these HDL particles in healthy normolipidemic women aged 21 to 35 years. The formulations contain comparable quantities of ethinyl estradiol (EE) and either desogestrel (DG), a minimally androgenic progestin, or levonorgestrel (LN), a more androgenic progestin. Lipid and lipoprotein levels were measured during the third week of the normal menstrual cycle and the sixth month of OC use. The DG/EE formulation significantly increased total cholesterol (C) 15%, triglyceride (TG) 99%, phospholipid (PL) 17%, apo A-I 28%, apo A-II 34%, apo B 21%, very-low-density lipoprotein cholesterol (VLDL-C) 238%, HDL-C 20%, and HDL3-C 28% (P < .02 to .005, n = 11), but not low-density lipoprotein cholesterol (LDL-C). The LN/EE formulation also increased total C 15%, TG 33%, apo A-I 15%, HDL3-C 21% (P < .05, n = 10), apo B 30% (P < .005), and, additionally, LDL-C 19% (P < .05). Both formulations increased Lp(AI,AII) (DG/EE, 34%, P < .005; LN/EE, 24%, P < .01). These changes reflected comparable increases of small (7.0 to 8.2 nm) and medium (8.2 to 9.2 nm) particles in the LN/EE group and a predominant increase of medium-sized particles in the DG/EE group. Also, in the LN/EE group but not the DG/EE group, there were fewer large (9.2 to 11.2 nm) particles. Lp(AI) increased only in the DG/EE group (25%, P = .075) and was due to the presence of more large particles. The level of Lp(AI) did not change in the LN/EE group, but the lipid/A-I ratio of these particles was lower (P = .012) and there were more small particles. Thus, triphasic OC formulations with progestins of different androgenicity had different effects on VLDL, LDL, and the level and composition of HDL particles with and without apo A-II, possibly reflecting estrogen/progestin/androgen balance. Estrogen dominance increases both Lp(AI,AII) and Lp(AI) and favors large Lp(AI) particles, while progestin/androgen dominance increases only Lp(AI,AII) and favors small particles. Because of the importance of HDL in the arterial wall physiology, OC formulations with different estrogen and progestin content may affect arterial wall health to a different extent.

译文

最近的观察结果表明,冠状动脉疾病 (CAD) 的风险与载脂蛋白 (apo) 定义的高密度脂蛋白 (HDL) 颗粒的两个主要人群的水平和组成有关: 同时含有apo A-I和apo A-II [Lp(AI,AII)] 和那些含有载脂蛋白A-I而没有载脂蛋白A-II [Lp(AI)]。虽然已知性激素会影响HDL,但它们对这些载脂蛋白定义的HDL颗粒的影响尚不清楚。我们已经确定了两种三相口服避孕药 (OC) 制剂对21至35岁健康降血脂妇女中这些HDL颗粒的影响。该制剂含有相当数量的乙炔雌二醇 (EE) 和去氧孕烯 (DG) (一种最低雄激素孕激素) 或左炔诺孕酮 (LN) (一种更雄激素孕激素)。在正常月经周期的第三周和使用OC的第六个月期间测量脂质和脂蛋白水平。DG/EE制剂显著增加总胆固醇 (C) 15% 、甘油三酯 (TG) 99% 、磷脂 (PL) 17% 、载脂蛋白A-I 28% 、载脂蛋白A-II 34% 、载脂蛋白B 21% 、极低密度脂蛋白胆固醇 (vldl-c) 238%,hdl-c 20% 和HDL3-C 28% (P <.02至.005,n = 11),但不是低密度脂蛋白胆固醇 (ldl-c)。LN/EE制剂还增加了总C 15% 、TG 33% 、apoa-I 15% 、HDL3-C 21% (P <0.05,n = 10) 、apob 30% (P < .005) 和另外的ldl-c 19% (P <.05)。两种制剂均增加Lp(AI,AII) (DG/EE,34%,P <.005; LN/EE,24%,P <.01)。这些变化反映了LN/EE组中小 (7.0至8.2 nm) 和中等 (8.2至9.2 nm) 颗粒的相当增加,以及DG/EE组中中等大小颗粒的主要增加。此外,在LN/EE组而不是DG/EE组中,较少的大 (9.2至11.2 nm) 颗粒。Lp(AI) 仅在DG/EE组中增加 (25%,P = .075),并且是由于存在更大的颗粒。LN/EE组的Lp(AI) 水平没有变化,但是这些颗粒的脂质/A-I比较低 (P = .012) 并且有更多的小颗粒。因此,具有不同雄激素性的孕激素的三相OC制剂对VLDL,LDL以及有和没有载脂蛋白A-II的HDL颗粒的水平和组成具有不同的影响,可能反映了雌激素/孕激素/雄激素平衡。雌激素优势会增加Lp(AI,AII) 和Lp(AI),并有利于大的Lp(AI) 颗粒,而孕激素/雄激素优势仅增加Lp(AI,AII) 并有利于小颗粒。由于HDL在动脉壁生理中的重要性,具有不同雌激素和孕激素含量的OC制剂可能在不同程度上影响动脉壁健康。

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