Are all estrogens the same?
Are all estrogens the same?
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DOI：
10.1016/j.maturitas.2003.11.009
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发表时间：
2004-04-15
期刊：
影响因子：
4.9
通讯作者：
Bennink, HJTC
中科院分区：
文献类型：
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作者：
Bennink, HJTC
本文重点探讨女性用于避孕、激素替代疗法 (HRT) 或预防骨质疏松症时，不同雌激素 (E) 是否具有不同性质的药效作用。在本文中，雌激素被定义为雌激素激动剂雌二醇(E2)、雌酮(E1)、雌三醇(E3)、结合马雌激素(CEE)、己烯雌酚(DES)和炔雌醇(EE)。选择性雌激素受体调节剂（SERM）已被排除在该分析之外，主要是因为缺乏与雌激素激动剂的比较（临床）数据。在解决雌激素激动剂的可比性问题时，一个主要问题是缺乏来自头对头纯雌激素比较研究的数据。比较研究几乎完全是用雌激素激动剂与一系列不同的孕激素 (P) 结合进行的，添加孕激素是为了保护子宫免受子宫内膜增生的影响。由于已知孕激素表现出不同的内在药效特性以及与雌激素的相互作用，因此当观察到不同组合 E/P 制剂之间的定性差异时，不可能判断雌激素所起的作用。总之，没有发现令人信服的证据表明所提到的雌激素有质的差异。显然，由于不同方面的差异，存在数量上的差异。受体亲和力、代谢（半衰期）和给药途径（透皮/阴道）。由于 DES 因具有致畸性而被废弃，因此所有复方 E/P 口服避孕药中使用的 EE 是目前最有效的雌激素激动剂。在 HRT 中，E2 和 CEE 对于治疗潮热和泌尿生殖道萎缩同样有效，并且优于任何其他治疗选择。对于预防骨质疏松症的长期治疗，甚至短期激素替代疗法，雌激素激动剂最近引起了激烈的争论，因为人们早已知道这种药物会略微增加患乳腺癌的风险。充分知情和个性化的治疗选择似乎是合适的解决方案。 (C) 2004 Elsevier Ireland Ltd. 保留所有权利。
This paper focuses on the question whether different estrogens (E) have different qualitative pharmacodynamic effects when used by women for contraception, Hormone Replacement Therapy (HRT) or prevention of osteoporosis. In this context estrogens have been defined as the estrogen agonists estradiol (E2), estrone (E1), estriol (E3), conjugated equine estrogens (CEE), diethylstilbestrol (DES) and ethinylestradiol (EE). Selective Estrogen Receptor Modulator's (SERM's) have been excluded from this analysis primarily because of lack of comparative (clinical) data with estrogen agonists. A major problem when addressing the issue of comparability of estrogen agonists is the lack of data from head-to-head estrogen-only comparative studies. Comparative studies have been performed almost exclusively with estrogen agonists combined with a series of different progestogens (P), that have been added to protect the uterus from endometrial hyperplasia. Since progestogens are known to exhibit different intrinsic pharmacodynamic properties and interactions with estrogens, it is impossible to judge which role the estrogen plays when qualitative differences between different combined E/P preparations are observed. In summary, no convincing evidence has been found that the estrogens mentioned differ qualitatively. Obviously quantitative differences are present due to differences in e.g. receptor affinity, metabolism (half life) and route of administration (transdermal/vaginal). Since DES has been discarded for human use due to teratogenicity, EE used in all combined E/P oral contraceptives is the most potent estrogen agonist available at present. In HRT, E2 and CEE are equally effective for the treatment of hot flushes and urogenital atrophy and superior to any other treatment option. For long term treatment to prevent osteoporosis and even for short term HRT, estrogen agonists are heavily debated recently because of a small increased risk of breast cancer, that has been known for a long time already. Well informed and individualised choice of treatment seems the appropriate solution. (C) 2004 Elsevier Ireland Ltd. All fights reserved.