Comparison of the metabolic effects of raloxifene and oral estrogen in postmenopausal and growth hormone-deficient women
Comparison of the metabolic effects of raloxifene and oral estrogen in postmenopausal and growth hormone-deficient women
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DOI：
10.1210/jc.2005-0173
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发表时间：
2005-07-01
影响因子：
5.8
通讯作者：
Ho, KKY
中科院分区：
文献类型：
--
作者：
Gibney, J;Johannsson, G;Ho, KKY
研究背景：雌激素影响肝脏的内分泌和代谢功能。口服雌激素减少IGF-I和抑制脂肪氧化，尽管增加GH分泌。本研究的目的是确定选择性雌激素受体调节剂是否显示出类似的效果，以及这些效果是否在GH缺乏（GHD）的妇女中由于GH反馈的丧失而被放大。设计：这是一项开放标签、随机、两阶段、交叉研究，（雷洛昔芬vs雌二醇）和组（正常vs. GHD）。设置：本研究的设置是一个临床研究单位。参与者：12名绝经后妇女和12名垂体功能减退症妇女参加了这项研究。干预：用17 β-雌二醇进行两次4周治疗（E2; 2 mg，随后4 mg）或雷洛昔芬（60毫克，然后120毫克），交叉后，交替治疗4周洗脱期。结果测量：内分泌[GH、IGF-I、IGFBP-3、GH结合蛋白和SHBG]和代谢（脂肪氧化）终点作为结果measurement.Results：E2以剂量依赖方式降低两组血清IGF-I水平，其作用大于雷洛昔芬（P < 0.05）。雷洛昔芬可降低GHD组的IGF-I水平（P < 0.001），但在绝经后组中无此作用。两组E2降低（P < 0.05），雷洛昔芬升高（P < 0.05），IGFBP-3水平升高（P < 0.05）。E2能增加绝经后妇女的GH（P < 0.05），而雷洛昔芬无此作用。E2和雷洛昔芬对IGF-I、IGFBP-3、IGF-I/IGFBP-3摩尔比、GH结合蛋白和SHBG的影响差异有统计学意义（P < 0.05）。结论：E2和雷洛昔芬对GHD患者肝脏内分泌有不同的影响，但对脂质氧化无明显影响。在GHD女性中看到的更大的影响可能是由内源性GH反馈的丧失所解释的。
Context: The endocrine and metabolic functions of the liver are affected by estrogen. Oral estrogen reduces IGF-I and suppresses fat oxidation despite augmenting GH secretion. The aim of this study was to determine whether selective estrogen receptor modulators display similar effects and whether these effects are magnified in GH-deficient (GHD) women because of the loss of GH feedback.Design: This was an open-label, randomized, two-period, crossover study comparing treatment (raloxifene vs. estradiol) and group (normal vs. GHD).Setting: The setting of this study was a clinical research unit.Participants: Twelve postmenopausal women and 12 women with hypopituitarism participated in this study.Intervention: Two 4-wk treatments with 17 beta-estradiol (E2; 2 mg, followed by 4 mg) or raloxifene (60 mg, followed by 120 mg) were given, crossing over to the alternate treatment after a 4-wk washout period.Outcome Measures: Endocrine [GH, IGF-I, IGF-binding protein-3 (IGFBP-3), GH-binding protein, and SHBG] and metabolic (fat oxidation) end points were used as outcome measures.Results: E2 reduced serum IGF-I levels in a dose-dependent manner in both groups, with effects greater (P < 0.05) than raloxifene. Raloxifene reduced IGF-I levels in the GHD group (P < 0.001), but not in the postmenopausal group. E2 reduced (P < 0.05), and raloxifene increased (P < 0.05), IGFBP-3 levels in both groups. E2, but not raloxifene, increased GH (P < 0.05) in postmenopausal women. The effects of E2 and raloxifene on IGF- I, IGFBP-3, IGF-I/IGFBP-3 molar ratio, GH-binding protein, and SHBG were significantly different (P < 0.05). E2 and raloxifene reduced (P < 0.05) fat oxidation equally in GHD, whereas the decrease in postmenopausal women was not significant.Conclusion: E2 and raloxifene exert different hepatic endocrine, but not lipid oxidative, effects. The greater effects seen in GHD women may be explained by the loss of endogenous GH feedback.