连续服用低剂量复方炔诺酮与复方18-甲基炔诺酮对妇女脂质代谢的远期影响

Long-term Effects of Low-dose Combined Norethisterone and Combined 18-metayl-Norethisterone on Lipid Metabolism in Healthy Women

目的 评价连续服用国产低剂量复方炔诺酮 (复方炔诺酮 )和低剂量复方 18 甲基炔诺酮 (复方 18 甲 ) ,对妇女脂质代谢的远期影响。方法 对连续服用复方炔诺酮 (复方炔诺酮组 ,16 7例 )和复方 18 甲 (复方 18 甲组 ,15 0例 ) 5～ 2 5年及同期放置宫内节育器 (IUD)的健康妇女 (对照组 ,131例 )进行血清甘油三酯 (TG)、总胆固醇 (TC)、高密度脂蛋白 (HDL C)、低密度脂蛋白 (LDL C)、载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)、脂蛋白a[Lp(a) ]的测定。 3组妇女的年龄、避孕药服用时间、体重指数、经济状况等 ,差异均无显著性。结果 与对照组比较 ,服用复方炔诺酮和复方 18 甲 5～ 2 5年妇女血清各项脂质水平均有不同程度的变化 ,两类口服避孕药使TG、HDL C显著升高 ;使ApoA1极显著升高。按不同避孕时间分析 ,服避孕药时间 <15年时 ,复方炔诺酮组TC为 (4 81± 0 70 )mmol/L、LDL C为 (2 6 7± 0 6 1)mmol/L ,均值显著低于复方 18 甲组的 (5 2 3± 1 0 2 )mmol/L ,(P <0 0 5 ) ;(3 0 7±0 80 )mmol/L(P <0 0 1) ,LDL C/HDL C (1 86± 0 5 9)也显著低于复方 18 甲组 (2 12± 0 6 5 ) (P <0 0 5 ) ;同时 ,ApoA1均值显著升高 ,复方炔诺酮组ApoA1/ApoB为 1 87± 0 5 8,高于复方 18 甲组 1 6 8±0 5 5。

Objective To assess the long term effects of combined oral contraceptive pills use on the mean of serum TG, TC, HDL C, LDL C, ApoA1, ApoB and Lp(a). Methods The study was carried out in 446 women grouped as combined norethisterone containing ethinylestradiol (EE) 35 μg and norethisterone 625 μg; combined 18 metayl norethisterone (norgestrel) containing EE 30 μg and 18 metayl norethisterone 300 μg for using 5～25 years, and control subjects wearing IUD for the corresponding period. The three groups were similar in age, body mass index (BMI), continued period of contraceptives use and income. Results The data showed that changes of varying degree of lipid and lipoprotein parameters were obvious in women of long term taking low dose combined norethisterone and norgestrel, compared with the control. The mean of TG, HDL C, ApoA1 were significantly increased simultaneously ( P< 0 05, P< 0 01), indicated multiple effects of two low dose Chinese COCs on lipid lipoprotein parameters. In addition, A significant increase ( P< 0 05) in Lp(a), an independent risk factor for cardiovascular disease, was found in norgestrel group.Further more, the results of stratified analysis to duration of contaceptives use showed that the mean of TC, LDL C, in the combined norethisterone use less than 15 years, after the adjusting for age, were significantly lower ( P< 0 05, P< 0 01) and the ratio of LDL C/HDL C was improved ( P< 0 05), compared with the Norgestrel; at the same time, the mean of ApoA1 was markedly higher ( P< 0 05) in combined norethisterone; the ratio of ApoA1/ApoB (1 87± 0 58) in the combined norethisterone group was superior to the ratio value (1 68±0 55) in norgestrel group. Conclusions These beneficial effects on lipid metabolism have been considered in dicators of potential cardiovascular protective effect of the combined norethisterone for taking pill less than 15 years, but these protective effects would be reduced with adverse change in lipid and lipoprotein parameters for taking combined norethisterone more than 15 years. In contrast, the mean of TC, LDL C, two known risk factors for cardiovascular system, in the norgestrel use less than 15 years, after the adjusting for age, were significantly increased ( P< 0 05, P< 0 01), and adverse changes in the TC/HDL C ratio ( P< 0 05) and ASI value, compared with the combined norethisterone; Lp(a) level was markedly higher in the norgestrel group than that in the control group( P< 0 05). These adverse effects on lipid metabolism have been considered indicators of potential cardiovascular harmful effect of low dose norgestrel.