Eden John
Royal Hospital for Women, UNSW School of Women's and Children's Health, Randwick, Australia.
Gynecol Endocrinol. 2005 Jul;21 Suppl 1:22-7. doi: 10.1080/09513590400030020.
For decades, hormone therapy (HT) has been the mainstay for managing menopausal symptoms. However, fear of breast cancer, as well as side-effects such as breast pain and return of vaginal bleeding, have made many women stop HT or refuse to take it. There is therefore a clear need for alternative treatments. Recent years have seen the development of hormonal agents with selective effects, such as tibolone. Tibolone has a unique mode of action and is described as a STEAR (Selective Tissue Estrogenic Activity Regulator). The main action of tibolone is mediated through two 3-hydroxy metabolites; small amounts of a third metabolite are also found in the circulation. In the brain, the effect is estrogenic and perhaps androgenic and, as such, tibolone relieves hot flushes and improves energy and sexual well-being. The uterus converts tibolone and its hydroxy metabolites into a Delta4 metabolite that has a progestogenic effect. In the breast, the metabolites of tibolone inhibit key enzymes that result in estrogen depletion within the breast itself. Clinically, tibolone does not stimulate the breast and it does not increase mammographic density. There are several key large, placebo-controlled international trials of tibolone currently underway, one of which (LIBERATE) aims to test the safety of tibolone (vs placebo) in women with a history of breast cancer who are suffering from climacteric symptoms.
几十年来，激素疗法（HT）一直是治疗更年期症状的主要方法。然而，对乳腺癌的恐惧以及诸如乳房疼痛和阴道出血复发等副作用，使得许多女性停止使用HT或拒绝服用。因此，显然需要替代疗法。近年来，出现了具有选择性作用的激素制剂，如替勃龙。替勃龙具有独特的作用方式，被描述为一种选择性组织雌激素活性调节剂（STEAR）。替勃龙的主要作用是通过两种3-羟基代谢物介导的；在循环中也发现了少量的第三种代谢物。在大脑中，其作用是雌激素样的，可能还有雄激素样作用，因此，替勃龙可缓解潮热并改善精力和性健康。子宫将替勃龙及其羟基代谢物转化为具有孕激素作用的Δ4代谢物。在乳腺中，替勃龙的代谢物抑制关键酶，从而导致乳腺自身雌激素耗竭。临床上，替勃龙不会刺激乳腺，也不会增加乳房X线摄影密度。目前正在进行几项关于替勃龙的关键大型国际安慰剂对照试验，其中一项试验（LIBERATE）旨在测试替勃龙（与安慰剂相比）对患有更年期症状且有乳腺癌病史的女性的安全性。
