Saxman K A, Barrett-Connor E L, Morton D J
Department of Family and Preventive Medicine, University of California-San Diego, La Jolla 92093-0607.
J Clin Endocrinol Metab. 1994 May;78(5):1059-63. doi: 10.1210/jcem.78.5.8175960.
The objective of this study was to identify abnormalities in lipid and carbohydrate metabolism in women taking thiazide diuretics and determine whether these abnormalities are mitigated by concurrent postmenopausal estrogen replacement therapy. The study design was cross-sectional; its setting was Rancho Bernardo, an upper middle-class community in southern California. The subjects included 1047 white nondiabetic postmenopausal women, aged 50-89 yr, categorized by the use of thiazide diuretic, estrogen replacement therapy, both, or neither. Medical history including behavior, verified medication use, height, weight, fasting chemistry and lipid panels, and a standardized oral glucose tolerance test with fasting and 2-h plasma glucose and serum insulin levels were determined. Compared with nonusers, women taking thiazides had significantly lower high density lipoprotein cholesterol levels and significantly higher fasting triglyceride, glucose, and insulin levels. Concomitant use of thiazide and estrogen yielded lipid profiles and fasting glucose and insulin levels similar to those of subjects receiving estrogen alone, i.e. elevated high density lipoproteins, decreased low density lipoproteins, and lower levels of fasting glucose and insulin compared with those in nonusers. However, thiazide-associated postchallenge glucose and insulin elevations were not modified by estrogen. These patterns were not explained by differences in age, body mass index, exercise, smoking, alcohol use, type or dose of thiazide diuretic, type of estrogen replacement, or serum potassium levels. We conclude that postmenopausal estrogen use masks thiazide-associated dyslipidemia and fasting elevations in glucose and insulin levels, but does not improve thiazide-associated postchallenge glucose intolerance and hyperinsulinemia. Modification of most of the untoward metabolic effects of thiazides in women taking postmenopausal estrogen could provide a new incentive for the use of this traditional antihypertensive in elderly women.
本研究的目的是确定服用噻嗪类利尿剂的女性脂质和碳水化合物代谢的异常情况，并确定这些异常是否可通过同时进行的绝经后雌激素替代疗法得到缓解。研究设计为横断面研究；研究地点是位于南加州的中上层阶级社区兰乔贝纳多。研究对象包括1047名年龄在50 - 89岁的白人非糖尿病绝经后女性，根据是否使用噻嗪类利尿剂、雌激素替代疗法、两者都用或两者都不用进行分类。记录了包括行为在内的病史、核实的用药情况、身高、体重、空腹生化指标和血脂指标，以及进行了标准化口服葡萄糖耐量试验，测定了空腹及2小时血浆葡萄糖和血清胰岛素水平。与未使用者相比，服用噻嗪类药物的女性高密度脂蛋白胆固醇水平显著降低，空腹甘油三酯、葡萄糖和胰岛素水平显著升高。同时使用噻嗪类药物和雌激素的女性的血脂谱、空腹血糖和胰岛素水平与仅接受雌激素治疗的受试者相似，即与未使用者相比，高密度脂蛋白升高，低密度脂蛋白降低，空腹血糖和胰岛素水平较低。然而，雌激素并不能改善噻嗪类药物引起的餐后血糖和胰岛素升高。这些模式无法通过年龄、体重指数、运动、吸烟、饮酒、噻嗪类利尿剂的类型或剂量、雌激素替代类型或血清钾水平的差异来解释。我们得出结论，绝经后使用雌激素掩盖了噻嗪类药物相关的血脂异常以及空腹血糖和胰岛素水平升高，但并不能改善噻嗪类药物相关的餐后葡萄糖不耐受和高胰岛素血症。改善绝经后服用雌激素的女性中噻嗪类药物的大多数不良代谢效应，可能会为在老年女性中使用这种传统抗高血压药物提供新的动力。
