Visser Monique, Coelingh Bennink Herjan J T
Pantarhei Bioscience, PO Box 464, 3700 AL Zeist, The Netherlands.
J Steroid Biochem Mol Biol. 2009 Mar;114(1-2):85-9. doi: 10.1016/j.jsbmb.2008.12.013. Epub 2009 Jan 9.
In this paper the potential clinical applications for the human fetal estrogen estetrol (E(4)) are presented based on recently obtained data in preclinical and clinical studies. In the past E(4) has been classified as a weak estrogen due to its rather low estrogen receptor affinity. However, recent research has demonstrated that due to its favorable pharmacokinetic properties, especially the slow elimination and long half-life, E(4) is an effective orally bioavailable estrogen agonist with estrogen antagonistic effects on the breast in the presence of estradiol. Based on the pharmacokinetic properties, the pharmacological profile and the safety and efficacy results in human studies, E(4) seems potentially suitable as a drug for human use in applications such as hormone replacement therapy (vaginal atrophy and vasomotor symptoms), contraception, osteoporosis and breast cancer.
本文基于近期在临床前和临床研究中获得的数据，介绍了人胎儿雌激素雌三醇（E₄）潜在的临床应用。过去，由于其雌激素受体亲和力相对较低，E₄被归类为弱雌激素。然而，最近的研究表明，由于其良好的药代动力学特性，尤其是消除缓慢和半衰期长，E₄是一种有效的口服生物利用雌激素激动剂，在存在雌二醇的情况下对乳腺具有雌激素拮抗作用。基于药代动力学特性、药理学特征以及人体研究中的安全性和有效性结果，E₄似乎有可能适用于激素替代疗法（阴道萎缩和血管舒缩症状）、避孕、骨质疏松症和乳腺癌等人类应用的药物。
