Effect of one-week treatment with vaginal estrogen preparations on serum estrogen levels in postmenopausal women
Effect of one-week treatment with vaginal estrogen preparations on serum estrogen levels in postmenopausal women
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DOI：
10.1097/gme.0b013e31817b6132
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发表时间：
2009-01-01
影响因子：
2.7
通讯作者：
Labrie, Claude
中科院分区：
文献类型：
--
作者：
Labrie, Fernand;Cusan, Leonello;Labrie, Claude
目的：大约50%的绝经后妇女患有阴道萎缩，其中很大一部分人选择阴道内注射局部作用的雌激素制剂，以避免全身暴露于雌激素及其相关的乳腺癌和子宫癌风险。本研究的主要目的是评估雌二醇和雌酮的系统生物利用度，以及两种最常用的阴道内雌激素制剂（Vagifem和Premarin霜）的药代动力学。设计：虽然基于免疫的分析以前不能提供绝经后妇女血清雌激素浓度的准确测量，但我们已经使用验证的质谱分析来测量每组10名绝经后妇女每天第七次使用25 μ g雌二醇（Vagifem）和1 g （0.625 mg）结合雌激素（Premarin）乳膏后24小时内血清雌二醇和雌酮的药代动力学。结果：每天给予雌二醇25 μ g或偶联雌激素乳膏1 g (0.625 mg)， 24小时内血清雌二醇水平由3提高到17 pg/mL，平均提高5.4倍。相反，使用Vagifem的血清雌酮增加150%，使用Premarin乳膏的血清雌酮增加500%。结论：目前使用经过验证的、准确的、敏感的雌激素质谱分析的数据显示，阴道丸和普雷马林乳膏，在每天治疗1周后，导致绝经后妇女血清雌二醇增加约5倍，从而表明其影响不太可能局限于阴道，并且在使用这些阴道内雌激素制剂后，预计会产生全身作用。
Objective: Approximately 50% of postmenopausal women suffer from vaginal atrophy, and a large proportion of them choose intravaginal estrogen preparations administered for local action to avoid systemic exposure to estrogens and its associated risk of breast and uterine cancer. The primary objective of this study was the evaluation of the systematic bioavailability of estradiol and estrone and the pharmacokinetics of two of the most frequently used intravaginal estrogen preparations, namely Vagifem and Premarin cream.Design: While immunobased assays could not previously provide accurate measurement of serum estrogen concentrations in postmenopausal women, we have used validated mass spectrometry assays to measure the pharmacokinetics of serum estradiol and estrone during the 24 hours following the seventh daily application of 25 mu g estradiol (Vagifem) and 1 g (0.625 mg) conjugated estrogens (Premarin) cream in 10 postmenopausal women in each group.Results: Serum estradiol was increased on average by 5.4-fold from 3 to 17 pg/mL during the 24-hour period after daily administration of 25 mu g estradiol or 1 g (0.625 mg) conjugated estrogens cream. Serum estrone, conversely, increased 150% with Vagifem and 500% with Premarin cream.Conclusions: The present data using validated, accurate, and sensitive mass spectrometry assays of estrogens show that the Vagifem pill and Premarin cream, after 1 week of daily treatment, cause an approximately fivefold increase in serum estradiol in postmenopausal women, thus indicating that the effects are unlikely to be limited to the vagina and that systemic actions are expected after application of these intravaginal estrogen preparations.