Goldstein S R, Siddhanti S, Ciaccia A V, Plouffe L
Department of Obstetrics and Gynecology, NYU Medical Center, NY 10016, USA.
Hum Reprod Update. 2000 May-Jun;6(3):212-24. doi: 10.1093/humupd/6.3.212.
Selective oestrogen receptor modulators (SERMs) are structurally diverse non-steroidal compounds that bind to oestrogen receptors and produce oestrogen agonist effects in some tissues and oestrogen antagonist effects in others. SERMs are being evaluated for a number of oestrogen-related diseases, including post-menopausal osteoporosis, hormone-dependent cancers, and cardiovascular disease. Several compounds that exhibit a SERM profile are currently available for clinical use, including clomiphene, tamoxifen, and toremifene (which are triphenylethylenes) and raloxifene (a benzothiophene). Clomiphene is used for the induction of ovulation in sub-fertile women attempting pregnancy. Tamoxifen and toremifene are both used to treat breast cancer. Tamoxifen may have beneficial effects on bone mineral density and serum lipids. The effects of toremifene on serum lipids are similar to that of tamoxifen. Both compounds have stimulatory effects on the endometrium. Raloxifene, indicated for the treatment and prevention of post-menopausal osteoporosis, has beneficial effects on bone mineral density and serum lipids, but does not increase the risk of endometrial hyperplasia or endometrial cancer. Recently, raloxifene was shown to reduce the incidence of vertebral fractures in otherwise healthy women with osteoporosis; in the same study, a reduced incidence of breast cancer was also observed. Similar to oestrogens, SERMs increase the incidence of venous thromboembolism. Several newer compounds that exhibit a SERM profile are also in clinical development, including other triphenylethylenes (droloxifene, idoxifene) and benzothiophenes (LY353381.HCl), benzopyrans (EM-800), and naphthalenes (CP-336,156).
选择性雌激素受体调节剂（SERM）是结构多样的非甾体化合物，可与雌激素受体结合，在某些组织中产生雌激素激动剂作用，而在其他组织中产生雌激素拮抗剂作用。目前正在对SERM进行多种与雌激素相关疾病的评估，包括绝经后骨质疏松症、激素依赖性癌症和心血管疾病。目前有几种具有SERM特性的化合物可供临床使用，包括氯米芬、他莫昔芬和托瑞米芬（均为三苯乙烯类）以及雷洛昔芬（一种苯并噻吩类）。氯米芬用于诱导不孕妇女排卵以助受孕。他莫昔芬和托瑞米芬均用于治疗乳腺癌。他莫昔芬可能对骨矿物质密度和血脂有有益作用。托瑞米芬对血脂的作用与他莫昔芬相似。这两种化合物对子宫内膜均有刺激作用。雷洛昔芬用于治疗和预防绝经后骨质疏松症，对骨矿物质密度和血脂有有益作用，但不会增加子宫内膜增生或子宫内膜癌的风险。最近的研究表明，雷洛昔芬可降低患有骨质疏松症的健康女性椎体骨折的发生率；在同一项研究中，还观察到乳腺癌的发生率有所降低。与雌激素相似，SERM会增加静脉血栓栓塞的发生率。还有几种具有SERM特性的新型化合物也正在进行临床开发，包括其他三苯乙烯类（屈洛昔芬、艾多昔芬）、苯并噻吩类（LY353381.HCl）、苯并吡喃类（EM - 800）和萘类（CP - 336,156）。
