Goodrest Croft Surgery, Yardley Wood, London, UK.
Clin Endocrinol (Oxf). 2013 Feb;78(2):297-302. doi: 10.1111/j.1365-2265.2012.04491.x.
To determine the effects of tibolone or oestradiol (E(2) )/norethisterone acetate (NETA) hormone replacement therapy on glucose and insulin metabolism in postmenopausal women.
Single-centre double-blind placebo-controlled randomized clinical trial.
SUBJECTS/METHODS: We randomized 105 healthy postmenopausal women to tibolone 2·5 mg daily, continuous combined oral E(2) 2 mg/NETA 1 mg daily or placebo over a 2-year study. We performed intravenous glucose tolerance tests (IVGTT) with measurements of plasma glucose, insulin and C-peptide concentrations and the IVGTT glucose elimination rate, k. Mathematical modelling was performed to determine measures of insulin sensitivity, S(i) , pancreatic insulin secretion and hepatic and plasma insulin elimination.
Tibolone decreased S(i) to 53-63% and k to 72-79% of baseline values but increased IVGTT phase 2 C-peptide concentrations 1·6-1·8-fold and pancreatic insulin secretion 2·2-2·4-fold, so overall IVGTT glucose concentrations were unaffected. Similar, but for k, significantly smaller changes in insulin and C-peptide secretion were seen with E(2) /NETA, also with no effect on overall IVGTT glucose concentrations.
Tibolone reduces insulin sensitivity. Healthy postmenopausal women seem able to compensate for this and maintain normal postload glucose concentrations, but it may not be advisable to prescribe tibolone to women with, or at increased risk for, diabetes.
观察替勃龙或雌二醇（E2）/醋酸炔诺酮（NETA）激素替代治疗对绝经后妇女糖和胰岛素代谢的影响。
单中心、双盲、安慰剂对照、随机临床试验。
受试者/方法：我们将 105 例健康绝经后妇女随机分为替勃龙 2.5mg 组、雌二醇 2mg/醋酸炔诺酮 1mg 组和安慰剂组，进行为期 2 年的研究。我们进行了静脉葡萄糖耐量试验（IVGTT），测量血浆葡萄糖、胰岛素和 C 肽浓度以及 IVGTT 葡萄糖消除率 k。采用数学模型评估胰岛素敏感性（S(i)）、胰岛β细胞胰岛素分泌和肝及血浆胰岛素清除。
替勃龙使 S(i)降低至基线值的 53%-63%，k 降低至 72%-79%，但使 IVGTT 第 2 相 C 肽浓度增加 1.6-1.8 倍，胰岛β细胞胰岛素分泌增加 2.2-2.4 倍，因此 IVGTT 葡萄糖浓度总体无变化。雌二醇/醋酸炔诺酮对胰岛素和 C 肽分泌的作用类似，但 k 的变化较小，对 IVGTT 葡萄糖浓度也无影响。
替勃龙降低胰岛素敏感性。健康绝经后妇女似乎能够对此进行代偿，维持正常餐后血糖浓度，但对于有糖尿病或糖尿病风险增加的妇女，不建议使用替勃龙。
