Palomba Stefano, Russo Tiziana, Orio Francesco, Sammartino Annalidia, Sbano Francesco Maria, Nappi Carmine, Colao Annamaria, Mastrantonio Pasquale, Lombardi Gaetano, Zullo Fulvio
Department of Obstetrics & Gynaecology, University of Catanzaro Magna Graecia, Catanzaro, Italy.
Hum Reprod. 2004 Feb;19(2):415-21. doi: 10.1093/humrep/deh053.
Although GnRH analogues are widely used to treat a variety of sex hormone-related diseases, little is known about their effect on metabolism. Therefore, we have evaluated the effect of a GnRH analogue, administered with or without raloxifene, on serum levels of lipoproteins, glucose, insulin and homocysteine (Hcy).
One hundred premenopausal women with symptomatic uterine leiomyomas were initially enrolled and randomized to receive 3.75 mg/28 days leuprolide acetate depot associated with 60 mg/day raloxifene hydrochloride (group A) or 1 placebo tablet/day (group B) for six cycles of 28 days. At entry and at cycle 6, subjects underwent anthropometric measurements, including body mass index and waist-to-hip ratio measurements, and blood chemistry assays for serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glucose, insulin, Hcy, vitamin B(12) and folate concentrations. Insulin resistance was evaluated with the homeostasis model assessment (HOMA) score.
Baseline parameters were similar in the two groups. At cycle 6, TC, HDL-C, LDL-C and TG levels were significantly increased (P < 0.05) in group B. In group A, LDL-C levels were unchanged, and TC, HDL-C and TG levels were increased (P < 0.05). Serum TC and LDL-C levels differed (P < 0.05) between the groups. Glucose levels were unchanged between and within groups, whereas insulin levels and HOMA scores increased (P < 0.05) versus baseline in group B. Post-treatment Hcy levels were higher (P < 0.05) versus baseline in group B; they were unchanged in group A. Serum vitamin B(12) and folate concentrations were unchanged in both groups.
GnRH analogues alter serum lipoprotein and Hcy levels and increase insulin resistance. These acute metabolic changes may be prevented or reduced by raloxifene.
尽管促性腺激素释放激素（GnRH）类似物被广泛用于治疗各种与性激素相关的疾病，但其对代谢的影响却知之甚少。因此，我们评估了一种GnRH类似物联合或不联合雷洛昔芬给药对血清脂蛋白、葡萄糖、胰岛素和同型半胱氨酸（Hcy）水平的影响。
最初纳入100名有症状的子宫平滑肌瘤的绝经前女性，并随机分为两组，一组接受每月一次3.75mg醋酸亮丙瑞林长效注射剂联合每日60mg盐酸雷洛昔芬（A组），另一组每日服用1片安慰剂（B组），为期6个周期，每个周期28天。在入组时和第6周期时，对受试者进行人体测量，包括体重指数和腰臀比测量，并检测血清总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、甘油三酯（TG）、葡萄糖、胰岛素、Hcy、维生素B12和叶酸浓度的血液生化指标。采用稳态模型评估（HOMA）评分评估胰岛素抵抗。
两组的基线参数相似。在第6周期时，B组的TC、HDL-C、LDL-C和TG水平显著升高（P<0.05）。在A组中，LDL-C水平未发生变化，而TC、HDL-C和TG水平升高（P<0.05）。两组之间的血清TC和LDL-C水平存在差异（P<0.05）。组间和组内的葡萄糖水平均未发生变化，而B组的胰岛素水平和HOMA评分相对于基线升高（P<0.05）。治疗后B组的Hcy水平相对于基线更高（P<0.05）；A组中该指标未发生变化。两组的血清维生素B12和叶酸浓度均未发生变化。
GnRH类似物会改变血清脂蛋白和Hcy水平，并增加胰岛素抵抗。雷洛昔芬可能预防或减轻这些急性代谢变化。
