A pharmacological review of selective oestrogen receptor modulators

Selective oestrogen receptor modulators (SERMs) are structurally diverse no n-steroidal compounds that bind to oestrogen receptors and produce oestroge n agonist effects in some tissues and oestrogen antagonist effects in other s. SERMs are being evaluated for a number of oestrogen-related diseases, in cluding past-menopausal osteoporosis, hormone-dependent cancers, and cardio vascular disease. Several compounds that exhibit a SERM profile are current ly available for clinical use, including clomiphene, tamoxifen, and toremif ene (which are triphenyrethylenes) and raloxifene (a benzothiophene), Clomi phene is used for the induction of ovulation in sub-fertile women attemptin g pregnancy, Tamoxifen and toremifene are both used to treat breast cancer, Tamoxifen may have beneficial effects on bone mineral density and serum li pids. The effects of toremifene on serum lipids are similar to that of tamo xifen. Both compounds have stimulatory effects on the endometrium. Raloxife ne, indicated for the treatment and prevention of post-menopausal osteoporo sis, has beneficial effects on bone mineral density and serum lipids, but d oes not increase the risk of endometrial hyperplasia or endometrial cancer. Recently, raloxifene was shown to reduce the incidence of vertebral fractu res in otherwise healthy women with osteoporosis; in the same study, a redu ced incidence of breast cancer was also observed. Similar to oestrogens, SE RMs increase the incidence of venous thromboembolism. Several newer compoun ds that exhibit a SERM profile are also in clinical development, including other triphenylethylenes (droloxifene, idoxifene) and benzothiophenes (LY35 3381 . HCl), benzopyrans (EM-800), and naphthalenes(CP-336,156).