Beyond estrogen: advances in tissue selective estrogen complexes and selective estrogen receptor modulators

Abstract

Selective estrogen receptor modulators (SERMs) are synthetic non-steroidal agents which have variable estrogen agonist and antagonist activities in different target tissues. Tamoxifen is an anti-estrogen in the breast used for treatment and prevention of breast cancer, with estrogen agonist activity in the uterus. Raloxifene prevents and treats osteoporosis and prevents breast cancer, and can be safely combined with vaginal but not systemic estrogen. The tissue selective estrogen complex combines conjugated equine estrogens (CEE) with the SERM bazedoxifene (BZA). The five Selective Estrogen Menopause and Response to Therapy studies, with up to 2 years of data, demonstrated that CEE/BZA 0.45 mg/BZA 20 mg improved vasomotor symptoms and vulvovaginal atrophy, prevented bone loss, and was neutral on breast tenderness, breast density, with breast cancer incidence similar to placebo. Protection against estrogen-induced endometrial hyperplasia and cancer was found, with similar amenorrhea rates to placebo. Ospemifene is approved to treat dyspareunia, with potential benefits on bone and the breast, while lasofoxifene is being developed to treat resistant estrogen receptor-positive breast cancer in women. Estetrol is an estrogen synthesized exclusively during pregnancy by the human fetal liver and initially considered a weak estrogen, but it appears to have dual weak estrogenic/anti-estrogenic features.

摘要

选择性雌激素受体调节剂(s)是一种合成的非甾体类药物, 它在不同的靶器官中可以发挥雌激素激动剂或拮抗剂活性。他莫昔芬作为一种抗雌激素药物被用来治疗和预防乳腺癌, 同时它对子宫有雌激素拮抗剂活性。雷洛昔芬用作预防和治疗骨质疏松和预防乳腺癌, 同时它联合阴道用雌激素也是安全的。组织选择性雌激素复合物是指结合雌激素(CEE)和SERM苯卓昔芬(BZA)。历时2年, 5个关于选择性雌激素绝经期疗效的研究表明, CEE/BZA 0.45 mg/BZA 20mg改善了血管舒缩症状和外阴阴道萎缩, 预防了骨丢失, 不引起乳房胀疼, 乳癌的发生率与安慰剂无差异, 而且不出现雌激素引起的内膜增生和内膜癌变, 闭经率与安慰剂无差异。奥培米芬用来治疗性交痛, 同时它对骨骼和乳房有益。拉索昔芬用于治疗抗雌激素受体阳性的乳癌。雌四醇是一种只在孕期由胎儿肝脏合成的雌激素, 起初被认为雌激素效能很弱, 但是人们逐渐发现了它弱雌激素/抗雌激素的双重效能。

KEYWORDS:

• Selective estrogen receptor modulators
• tissue selective estrogen complex
• bazedoxifene
• conjugated estrogens
• bazedoxifene/conjugated estrogens
• tamoxifen
• raloxifene
• estetrol

Conflict of interest

The authors report no conflict of interest.

Source of funding

Nil.