Verhoeven Marieke O, Hemelaar Majoie, Teerlink Tom, Kenemans Peter, van der Mooren Marius J
Project Aging Women and the Institute for Cardiovascular Research-Vrije Universiteit, Department of Obstetrics & Gynecology, VU University Medical Center, Amsterdam, The Netherlands.
Atherosclerosis. 2007 Nov;195(1):181-8. doi: 10.1016/j.atherosclerosis.2006.09.018. Epub 2006 Nov 7.
Oral estrogens reduce asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, and an independent risk factor for cardiovascular disease. This study was conducted to compare the effect on ADMA between intranasal and oral 17beta-estradiol (E2) combined with norethisterone (acetate) (NET(A)) administration in postmenopausal women.
In a two-center, randomized, double-blind, comparative study 90 healthy postmenopausal women (age 56.6+/-4.7 years) received daily continuous combined intranasal E2/NET 175 microg/275 microg (n=47) or oral E2/NETA 1 mg/0.5 mg (n=43) for one year. At baseline, week 12 and 52, plasma concentrations of ADMA, arginine and symmetric dimethylarginine (SDMA) were measured by high-performance liquid chromatography.
Oral E2/NETA reduced ADMA concentrations (-7.4%; 95% confidence interval (CI) -10.4 to -4.4%), while intranasal E2/NET had no effect (-0.8%; 95% CI -3.7 to 2.1%) after 52 weeks. In both groups, arginine was transiently decreased compared to baseline at week 12 (intranasal: -6.1%; 95% CI -9.1 to -3.0%; oral: -6.5%; 95% CI -10.9 to -2.1%). Only oral E2/NETA reduced SDMA concentrations.
Oral administration of E2/NETA reduced ADMA and SDMA concentrations, whereas intranasal administration did not. Both treatments transiently reduced arginine. The decrease in ADMA by oral estrogens could be a key phenomenon in the modulation of nitric oxide synthesis by postmenopausal hormone therapy.
口服雌激素可降低不对称二甲基精氨酸（ADMA）水平，ADMA是一氧化氮合酶的内源性抑制剂，也是心血管疾病的独立危险因素。本研究旨在比较绝经后女性经鼻和口服17β-雌二醇（E2）联合炔诺酮（醋酸酯）（NET(A)）给药对ADMA的影响。
在一项双中心、随机、双盲、对照研究中，90名健康绝经后女性（年龄56.6±4.7岁）连续一年每日接受经鼻E2/NET 175微克/275微克（n = 47）或口服E2/NETA 1毫克/0.5毫克（n = 43）治疗。在基线、第12周和第52周时，采用高效液相色谱法测定血浆中ADMA、精氨酸和对称二甲基精氨酸（SDMA）的浓度。
52周后，口服E2/NETA可降低ADMA浓度（-7.4%；95%置信区间（CI）-10.4至-4.4%），而经鼻E2/NET则无此作用（-0.8%；95% CI -3.7至2.1%）。在两组中，第12周时精氨酸水平与基线相比均短暂下降（经鼻：-6.1%；95% CI -9.1至-3.0%；口服：-6.5%；95% CI -10.9至-2.1%）。只有口服E2/NETA可降低SDMA浓度。
口服E2/NETA可降低ADMA和SDMA浓度，而经鼻给药则无此效果。两种治疗方法均可短暂降低精氨酸水平。口服雌激素导致的ADMA降低可能是绝经后激素治疗调节一氧化氮合成的关键现象。
