Contraceptive steroids: modifications of carbohydrate and lipid metabolism.
Contraceptive steroids: modifications of carbohydrate and lipid metabolism.
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避孕类固醇：改变碳水化合物和脂质代谢。
DOI：
10.1016/0026-0495(73)90056-5
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发表时间：
1973
期刊：
影响因子：
--
通讯作者：
P. Beck
中科院分区：
文献类型：
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作者：
P. Beck
尽管长期服用避孕药类固醇可能会产生多种代谢变化，但它们对碳水化合物和脂肪代谢的影响似乎与接受者的年龄和代谢性疾病的易感性以及所采用的节育制剂中雌激素、去甲睾酮和孕酮衍生物的数量和相对比例有关。在健康的健康年轻女性中，单独服用合成雌孕激素衍生物或去甲睾酮衍生物并不能持续改变葡萄糖或胰岛素代谢，如隔夜禁食或葡萄糖注射后的血糖或胰岛素浓度所评估的那样。然而，甲孕醇或乙炔雌二醇与去甲睾酮衍生物同时给药会导致葡萄糖耐量下降，这在同时给药合成雌孕酮衍生物时观察不到。避孕药产生的葡萄糖耐量变化叠加在随年龄增长而观察到的葡萄糖耐量恶化上。此外，胰腺胰岛素储备不足的女性在接受避孕类固醇治疗时，似乎比正常女性更有可能出现糖耐量异常，尽管使用避孕药的需要胰岛素的糖尿病患者似乎并不经常出现葡萄糖稳态恶化。在正常女性和恒河猴中，同时服用甲孕酮-去甲睾酮衍生物通常会增强外周循环胰岛素对葡萄糖挑战的反应，而单独使用避孕类固醇和同时服用合成雌孕激素衍生物通常对循环胰岛素浓度影响很小。然而，恒河猴并不是研究避孕药类固醇代谢影响的理想模型，因为它的葡萄糖耐量在同时服用甲孕醇和炔诺酮时有所改善。目前还没有其他合适的动物模型来研究避孕类固醇对碳水化合物代谢的影响。雌激素治疗会导致空腹血清甘油三酯浓度升高。去甲睾酮衍生物(但不是17个α-乙酰氧孕酮衍生物)可以抵消雌激素的高甘油三酯效应。这两种影响似乎都与剂量有关。避孕药引起的高甘油三酯血症主要是由于肝脏产生的甘油三酯增加，尽管避孕药中的雌激素成分似乎也降低了甘油三酯的血浆清除量。避孕药产生的血清胆固醇浓度的变化很小，并且与患者的年龄有关。在40岁以上的妇女中，服用避孕药后血清总胆固醇浓度降低；而在40岁以下的妇女中，血清总胆固醇浓度上升。当血清总胆固醇浓度增加时，它们似乎与去甲睾酮或孕酮衍生物的摄入量有关。本文讨论了这些复杂的避孕类固醇引起的碳水化合物和脂肪代谢变化与心血管疾病长期发展的可能关系，尽管涉及的机制尚不清楚。
Although chronic ingestion of contraceptive steroids may produce a variety of metabolic changes, their effect on carbohydrate and lipid metabolism appears to be related to the age and predisposition to metabolic disease of the recipient and to the amounts and relative proportions of estrogen, nortestosterone, and progesterone derivatives in the birth control preparations employed.In healthy intact young women, the separate administration of either synthetic estrogensorprogesterone derivativesornortestosterone derivatives does not consistently alter glucose or insulin metabolism as assessed by serum glucose or insulin concentrations after overnight fasting or following glucose administration. However, the concurrent administration of mestranol or ethinyl estradiol with a nortestosterone derivative produces deterioration of glucose tolerance, which is not observed during concurrent synthetic estrogenprogesterone derivative administration. The changes in glucose tolerance produced by birth control pills are superimposed on the deterioration of glucose tolerance observed with aging. Also, women with borderline pancreatic insulin reserve appear more likely to develop abnormal glucose tolerance than normal women when challenged with contraceptive steroids, although deterioration of glucose homeostasis does not seem to occur frequently in insulin-requiring diabetics using birth control pills.Concurrent mestranol-nortestosterone derivative administration generally enhances the peripheral circulating insulin response to a glucose challenge in normal women and in rhesus monkeys, whereas the individual contraceptive steroids and concurrent synthetic estrogen-progesterone derivative administration generally produce little measurable effect on circulating insulin concentrations. However, the rhesus monkey is not an ideal model for studying the metabolic effects of contraceptive steroids because its glucose toleranceimproveswith concurrent mestranol-norethindrone administration. No other suitable animal model has been developed for studying the effect of contraceptive steroids on carbohydrate metabolism.Estrogen administration leads to increased fasting serum triglyceride concentrations. Nortestosterone derivatives (but not 17 α-acetoxyprogesterone derivatives) counteract the hypertriglyceridemic effect of estrogens. Both of these effects appear to be dose-related. Contraceptive steroid-inducd hypertriglyceridemia primarily appears to be due to increased hepatic production of triglycerides, although plasma clearance of the triglycerides also seems to be reduced by the estrogen component of contraceptive steroids.Changes in serum cholesterol concentrations produced by birth control pills are small and are related to the age of the patient. In womenover40, total serum cholesterol concentrationsdecreaseduring birth control pill use; in womenunder40, theyincrease. When increases in total serum cholesterol concentrations occur, they appear to be related to the amount of nortestosterone or progesterone derivative ingested.The possible relationship of these complex contraceptive steroid-induced changes in carbohydrate and lipid metabolism to the long-term development of cardiovascular diseases is discussed, although the mechanisms involved remain obscure.