Fineberg S E
Indiana University School of Medicine, Department of Medicine, Indianapolis 46202, USA.
Drugs Aging. 2000 Dec;17(6):453-61. doi: 10.2165/00002512-200017060-00003.
Despite evidence that supports the beneficial effects of postmenopausal hormone replacement therapy (HRT), concerns remain about its possible adverse effects. However, entry into the postmenopausal state is associated with many characteristics of the insulin resistance syndrome, including increased cardiovascular morbidity and mortality, accretion of generalised and visceral adiposity and insulin resistance. Studies carried out in postmenopausal women have revealed that an increase in visceral obesity is associated with an increase in androgenicity that, in turn, is associated with type 2 (non-insulin-dependent) diabetes mellitus. Short term studies of HRT containing conjugated estrogens (CEE) and medroxyprogesterone (MPA) have shown prevention of the accretion of visceral fat. However, longer term studies using other techniques suggest that these effects may be evanescent. A few trials suggest that oral estrogen therapy reduces postmenopausal insulin resistance, as suggested by reductions in fasting insulin and glucose levels and an increase in glucose metabolism rates, whereas most studies do not show an adverse effect upon carbohydrate metabolism. MPA may decrease these beneficial effects. Transdermal estrogen is essentially neutral with regard to insulin sensitivity and oral estradiol (17beta-estradiol) may also be neutral or enhance sensitivity. Different progestogens vary in their effects upon carbohydrate metabolism. The Postmenopausal Estrogen/Progestogen Intervention (PEPI) Study was a prospective, 3-year, randomised trial in 875 women that compared placebo, unopposed CEE, CEE plus continuous MPA, CEE plus cyclical MPA, and CEE plus cyclical micronised progesterone. Fasting insulin and glucose levels decreased significantly by 16.1% and 0.122 mmol/L, respectively, in all drug treatment groups. However, after a 75g glucose load, glucose levels at 2 hours increased by 0.33 mmol/L in the active treatment groups without a corresponding increase in insulin levels. No beneficial effects on waist/hip ratio could be demonstrated. Data from the PEPI trial also suggested that the maximum benefit regarding carbohydrate metabolism was achieved in patients who were the most hyperglycaemic and hyperinsulinaemic at the start of therapy. It can be concluded, therefore, that HRT has few, if any, harmful effects on carbohydrate metabolism and that it may be of benefit in women in modifying the long term complications of the postmenopausal state.
尽管有证据支持绝经后激素替代疗法（HRT）的有益效果，但人们仍对其可能的不良反应存在担忧。然而，进入绝经后状态与胰岛素抵抗综合征的许多特征相关，包括心血管疾病发病率和死亡率增加、全身及内脏脂肪堆积以及胰岛素抵抗。对绝经后女性进行的研究表明，内脏肥胖增加与雄激素化增加相关，而雄激素化又与2型（非胰岛素依赖型）糖尿病相关。含结合雌激素（CEE）和甲羟孕酮（MPA）的HRT短期研究显示可预防内脏脂肪堆积。然而，使用其他技术的长期研究表明这些效果可能是短暂的。一些试验表明，口服雌激素疗法可降低绝经后胰岛素抵抗，空腹胰岛素和血糖水平降低以及葡萄糖代谢率增加表明了这一点，而大多数研究并未显示对碳水化合物代谢有不良影响。MPA可能会降低这些有益效果。经皮雌激素对胰岛素敏感性基本呈中性，口服雌二醇（17β - 雌二醇）也可能呈中性或增强敏感性。不同的孕激素对碳水化合物代谢的影响各不相同。绝经后雌激素/孕激素干预（PEPI）研究是一项针对875名女性的前瞻性、为期3年的随机试验，比较了安慰剂、单纯CEE、CEE加持续MPA、CEE加周期性MPA以及CEE加周期性微粉化孕酮。所有药物治疗组的空腹胰岛素和血糖水平分别显著降低了16.1%和0.122 mmol/L。然而，在给予75g葡萄糖负荷后，活性治疗组2小时时的血糖水平升高了0.33 mmol/L，而胰岛素水平没有相应增加。未显示对腰臀比有有益影响。PEPI试验的数据还表明，在治疗开始时血糖和胰岛素水平最高的患者中，在碳水化合物代谢方面获得的益处最大。因此，可以得出结论，HRT对碳水化合物代谢几乎没有有害影响，并且可能对女性改善绝经后状态长期并发症有益。
