Skouby S O, Andersen O, Petersen K R, Mølsted-Pedersen L, Kühl C
Department of Obstetrics and Gynecology Y, Rigshospitalet, Copenhagen, Denmark.
Am J Obstet Gynecol. 1990 Jul;163(1 Pt 2):343-8. doi: 10.1016/0002-9378(90)90579-v.
Although the available scientific data on the undesired metabolic effects of sex steroids have accumulated rapidly, most are of a descriptive nature, and only a few studies elucidate the impact at the cellular level and the possible interrelationship between different metabolic systems. This review summarizes the influence of different contraceptive steroid combinations on glucose metabolism and points to the possible mechanisms behind a disturbance of the euglycemic homeostasis with a concomitant change in lipid metabolism. Today the general concept is that the influence of combined sex steroid products on glucose metabolism is mainly caused by the progestogen components, although artificial estrogens may act synergistically. The diabetogenic effects of the progestogens make it important to consider the development during the last decade of the new more selective progestogens of the gonane type. From recent studies it seems, however, that intake of contraceptive combinations of ethinyl estradiol in combination with these types of gonanes, such as desogestrel and gestodene, may also be accompanied by increased insulin resistance, specifically, a hyperinsulinemic response to a glucose challenge despite unchanged glucose values compared with a baseline test. This is similar to observations made with combinations of ethinyl estradiol and other more traditional types of progestogens of the gonane and estrane type. It is conceivable that the diabetogenic effects of the progestogens are caused by a change in insulin receptor binding or a postreceptor defect in the cellular insulin action. The clinical implications of the diabetogenic effects of the sex steroids are hard to interpret, but more long-term exposure of arterial tissue to elevated concentrations of glucose and insulin results in inhibition of lipolysis and synthesis of cholesterol and triglycerides, which result in the development of lipid-filled lesions--fatty streaks--similar to those of early atherosclerosis.
尽管关于性类固醇不良代谢影响的现有科学数据迅速积累，但大多数是描述性的，只有少数研究阐明了其在细胞水平的影响以及不同代谢系统之间可能的相互关系。本综述总结了不同避孕类固醇组合对葡萄糖代谢的影响，并指出了正常血糖稳态紊乱伴脂质代谢变化背后的可能机制。如今的普遍观点是，联合性类固醇产品对葡萄糖代谢的影响主要由孕激素成分引起，尽管人工合成雌激素可能起协同作用。孕激素的致糖尿病作用使得考虑过去十年中新型更具选择性的孕烷类孕激素的发展变得很重要。然而，从最近的研究来看，摄入乙炔雌二醇与这些类型的孕烷类（如去氧孕烯和孕二烯酮）的避孕组合，也可能伴随着胰岛素抵抗增加，具体而言，尽管与基线测试相比血糖值未变，但对葡萄糖刺激会出现高胰岛素血症反应。这与乙炔雌二醇和其他更传统的孕烷类及雌甾烷类孕激素组合的观察结果相似。可以想象，孕激素的致糖尿病作用是由胰岛素受体结合的变化或细胞胰岛素作用中的受体后缺陷引起的。性类固醇致糖尿病作用的临床意义难以解释，但动脉组织长期暴露于升高的葡萄糖和胰岛素浓度会导致脂肪分解受抑制以及胆固醇和甘油三酯合成受抑制，从而导致脂质填充病变——脂肪条纹——的形成，类似于早期动脉粥样硬化的病变。
