Notelovitz Morris
MedGenMed. 2007 Jan 3;9(1):2.
Although the menopause is a generic physiologic event, its biology is variable and specific to a given individual. Genetically determined distribution and polymorphism of relevant hormone receptors, enzymes, and various cofactors are the biologic mechanisms controlling an individual's clinical response to endogenous and prescribed hormones. Advances in molecular biology have led to the development of newer pharmacologic agents that are tailored to meet specific therapeutic objectives, based on the hormonal biology of relevant organs. Tibolone, an analogue of the progestin, norethynodrel, is a drug with tissue-specific effects on receptors and enzymes that influences the synthesis and metabolism of endogenous estrogen, progesterone, and androgen. This is achieved via the intestinal bioconversion of tibolone into metabolites that have tissue-specific agonistic and/or antagonistic estrogenic (3alpha and 3beta hydroxytibolone) and progestogenic/androgenic (delta4 tibolone) properties. The postmenopausal synthesis and metabolism of estrogen and androgen are briefly reviewed with particular reference to sex steroid activity in various target organs. On the basis of this hormonal physiology, the clinical utility of tibolone is reviewed as a therapeutic agent for the treatment of the symptomatic menopause. The effects of tibolone on bone health and osteoporosis, cardiovascular disease, the breast, and the endometrium are summarized, and its role in clinical practice is reviewed.
尽管绝经是一种普遍的生理现象，但其生物学特性因人而异。相关激素受体、酶及各种辅助因子的基因决定的分布和多态性是控制个体对内源性和处方激素临床反应的生物学机制。分子生物学的进展促使开发出更新型的药物制剂，这些制剂根据相关器官的激素生物学特性进行定制，以实现特定的治疗目标。替勃龙是孕激素炔诺酮的类似物，是一种对受体和酶具有组织特异性作用的药物，它会影响内源性雌激素、孕激素和雄激素的合成与代谢。这是通过替勃龙在肠道内生物转化为具有组织特异性激动和/或拮抗雌激素特性（3α和3β羟基替勃龙）以及孕激素/雄激素特性（δ4替勃龙）的代谢产物来实现的。本文简要回顾了绝经后雌激素和雄激素的合成与代谢，特别提及了各种靶器官中的性类固醇活性。基于这种激素生理学，本文回顾了替勃龙作为治疗有症状绝经的治疗药物的临床应用。总结了替勃龙对骨骼健康和骨质疏松症、心血管疾病、乳腺及子宫内膜的影响，并对其在临床实践中的作用进行了回顾。
