Coelingh Bennink Herjan J T
Pantarhei Bioscience, Institute for Clinical Concept Research in Reproductive Medicine, Pantarhei Bioscience, Zeist, The Netherlands.
Maturitas. 2004 Apr 15;47(4):269-75. doi: 10.1016/j.maturitas.2003.11.009.
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.
本文聚焦于一个问题，即不同雌激素（E）在女性用于避孕、激素替代疗法（HRT）或预防骨质疏松时是否具有不同的定性药效学作用。在此背景下，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）被排除在本分析之外，主要是因为缺乏与雌激素激动剂的比较（临床）数据。在探讨雌激素激动剂可比性问题时，一个主要问题是缺乏仅雌激素的直接比较研究的数据。几乎所有的比较研究都是将雌激素激动剂与一系列不同的孕激素（P）联合进行的，添加孕激素是为了保护子宫免受子宫内膜增生的影响。由于已知孕激素具有不同的内在药效学特性以及与雌激素的相互作用，所以当观察到不同的E/P联合制剂之间存在定性差异时，无法判断雌激素起到了何种作用。总之，尚未找到令人信服的证据表明上述雌激素存在定性差异。显然，由于例如受体亲和力、代谢（半衰期）和给药途径（经皮/阴道）等方面的差异，存在定量差异。由于DES具有致畸性已被弃用，目前所有E/P口服避孕药中使用的EE是现有最有效的雌激素激动剂。在HRT中，E2和CEE在治疗潮热和泌尿生殖系统萎缩方面同样有效，且优于任何其他治疗选择。由于长期以来已知雌激素激动剂会使乳腺癌风险略有增加，因此对于预防骨质疏松的长期治疗甚至短期HRT，近期都存在激烈争论。明智且个体化的治疗选择似乎是合适的解决方案。
