Ginsburg E S, Walsh B, Greenberg L, Price D, Chertow G M, Owen W F
Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Kidney Int. 1998 Oct;54(4):1344-50. doi: 10.1046/j.1523-1755.1998.00087.x.
Patients with ESRD have excessive cardiovascular morbidity and mortality. In postmenopausal women with normal renal function, estrogen replacement therapy decreases cardiovascular mortality by 50%, in part because of their beneficial effects on the lipoprotein profile. Because of similarities in the lipoprotein profile between healthy, postmenopausal women, and women with ESRD, we examined the effects of estrogen replacement on lipoproteins in 11 postmenopausal women with ESRD.
In a randomized, placebo-controlled crossover study (8 week treatment arms) using 2 mg daily of oral, micronized estradiol, 11 postmenopausal women with ESRD were treated. Neither baseline lipid nor lipoprotein abnormalities were used as entry criteria for study participation.
Blood estradiol levels were 19 +/- 4 with placebo and 194 +/- 67 pg/ml (P = 0.024) with estradiol treatment. Total HDL cholesterol concentrations increased from 52 +/- 19 mg/dl to 61 +/- 20 mg/dl (16%), with placebo and estradiol treatments, respectively (P = 0.002). Apolipoprotein A1 increased by 24.6% (P = 0.0002) with estradiol intervention. HDL2 concentrations were 19 +/- 13 with placebo and 24 +/- 16 with estradiol treatment (P = 0.046). There were no differences in total or LDL cholesterol, other lipoprotein fractions including Lp(a), and triglycerides with 2 mg daily estradiol treatment. No significant side effects were observed.
Therefore, using standard dosage regimens for estrogen replacement therapy in postmenopausal women with ESRD, HDL cholesterol is increased to an extent that would be expected to improve their cardiovascular risk profile. Further studies are needed to assess whether estrogen replacement therapy decreases the incidence or severity of cardiovascular disease in ESRD patients to a similar degree compared with other women.
终末期肾病(ESRD)患者存在过度的心血管疾病发病率和死亡率。在肾功能正常的绝经后女性中,雌激素替代疗法可使心血管疾病死亡率降低50%,部分原因是其对脂蛋白谱有有益影响。由于健康绝经后女性与ESRD女性的脂蛋白谱存在相似性,我们研究了雌激素替代疗法对11例绝经后ESRD女性脂蛋白的影响。
采用每日口服2毫克微粒化雌二醇进行随机、安慰剂对照交叉研究(每个治疗组为期8周),对11例绝经后ESRD女性进行治疗。研究参与的入选标准未采用基线血脂或脂蛋白异常情况。
服用安慰剂时血雌二醇水平为19±4,服用雌二醇治疗时为194±67皮克/毫升(P = 0.024)。安慰剂组和雌二醇治疗组的总高密度脂蛋白(HDL)胆固醇浓度分别从52±19毫克/分升增至61±20毫克/分升(16%)(P = 0.002)。雌二醇干预使载脂蛋白A1增加了24.6%(P = 0.0002)。HDL2浓度在安慰剂组为19±13,在雌二醇治疗组为24±16(P = 0.046)。每日服用2毫克雌二醇治疗时,总胆固醇或低密度脂蛋白胆固醇、包括脂蛋白(a)在内的其他脂蛋白组分以及甘油三酯均无差异。未观察到明显副作用。
因此,在绝经后ESRD女性中采用标准剂量方案进行雌激素替代疗法,可使HDL胆固醇升高至预期能改善其心血管疾病风险状况的程度。需要进一步研究来评估雌激素替代疗法与其他女性相比,是否能同等程度地降低ESRD患者心血管疾病的发病率或严重程度。