Medical management of metabolic dysfunction in PCOS.
Medical management of metabolic dysfunction in PCOS.
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DOI：
10.1016/j.steroids.2011.11.014
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发表时间：
2012-03-10
期刊：
影响因子：
2.7
通讯作者：
Duleba AJ
中科院分区：
文献类型：
--
作者：
Duleba AJ
多囊卵巢综合征（PCOS）与代谢紊乱有关，包括胰岛素抵抗、血脂异常、全身炎症和内皮功能障碍。越来越需要开发药物干预措施来改善PCOS女性的代谢功能。已在PCOS患者中测试的药物包括二甲双胍、噻唑烷二酮类、阿卡波糖、纳洛酮、奥利司他、维生素D和他汀类药物。二甲双胍可降低肝硬化和游离脂肪酸氧化，同时增加外周葡萄糖摄取。PCOS的早期研究表明，二甲双胍间接降低胰岛素水平，血脂异常和全身炎症;然而，最近的安慰剂对照试验未能证明显着的代谢益处。噻唑烷二酮类主要通过增加外周葡萄糖摄取起作用。大多数PCOS研究表明噻唑烷二酮类药物可降低胰岛素抵抗，但对血脂异常的影响令人失望。使用噻唑烷二酮类药物与体重增加和主要并发症有关。阿卡波糖减少多糖的消化。多囊卵巢综合征的研究表明阿卡波糖对胰岛素敏感性的影响不一致，对血脂异常无明显改善。纳洛酮可降低食欲并调节胰岛素释放;在PCOS中使用纳洛酮可降低高胰岛素血症。奥利司他减少膳食脂肪的吸收;多囊卵巢综合征的研究表明对胰岛素敏感性有益。维生素D可能会改善胰岛素敏感性，但在PCOS的血脂混合结果已被报道。他汀类药物是调节甲羟戊酸途径的关键酶的竞争性抑制剂;其作用与降低胆固醇产生以及抗炎和抗氧化特性有关。在PCOS女性中，他汀类药物可降低高雄激素血症，改善血脂，减少全身炎症，而对胰岛素敏感性的影响是可变的。妊娠期禁用他汀类药物。
Polycystic ovary syndrome (PCOS) is associated with metabolic derangements including insulin resistance, dyslipidemia, systemic inflammation and endothelial dysfunction. There is a growing need to develop pharmacologic interventions to improve metabolic function in women with PCOS. Medications that have been tested in patients with PCOS include metformin, thiazolidinediones, acarbose, naltrexone, orlistat, vitamin D and statins. Metformin decreases hepatic gluconeogenesis and free fatty acid oxidation while increasing peripheral glucose uptake. Early studies in PCOS suggested that metformin indirectly reduces insulin level, dyslipidemia and systemic inflammation; however, recent placebo-controlled trials failed to demonstrate significant metabolic benefit. Thiazolidinediones act primarily by increasing peripheral glucose uptake. Most studies in PCOS have demonstrated that thiazolidinediones reduce insulin resistance; however, effects on dyslipidemia were disappointing. Use of thiazolidinediones is associated with weight gain and major complications. Acarbose reduces digestion of polysaccharides. Studies in PCOS yielded inconsistent effects of acarbose on insulin sensitivity and no significant improvement of dyslipidemia. Naltrexone reduces appetite and modulates insulin release; its use in PCOS may reduce hyperinsulinemia. Orlistat decreases absorption of dietary fats; studies in PCOS suggest beneficial effects on insulin sensitivity. Vitamin D may improve insulin sensitivity but mixed results on lipid profile in PCOS have been reported. Statins are competitive inhibitors of the key enzyme regulating the mevalonate pathway; their effects are related to reduced cholesterol production as well as anti-inflammatory and anti-oxidant properties. In women with PCOS, statins reduce hyperandrogenism, improve lipid profile and reduce systemic inflammation while the effects on insulin sensitivity are variable. Use of statins is contraindicated in pregnancy.
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