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Concept
Selective estrogen receptor modulator
Résumé
Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonist/antagonists (ERAAs), are a class of drugs that act on the estrogen receptor (ER). A characteristic that distinguishes these substances from pure ER agonists and antagonists (that is, full agonists and silent antagonists) is that their action is different in various tissues, thereby granting the possibility to selectively inhibit or stimulate estrogen-like action in various tissues.
SERMs are used for various estrogen-related diseases, including treatment of ovulatory dysfunction in the management of infertility, treatment and prevention of postmenopausal osteoporosis, treatment and reduction in risk of breast cancer and treatment of dyspareunia due to menopause. SERM is also used in combination with conjugated estrogens indicated for the treatment of estrogen deficiency symptoms, and vasomotor symptoms associated with menopause. SERMs are used dependent on their pattern of action in various tissues:
Tamoxifen is a first-line hormonal treatment of ER-positive metastatic breast cancer. It is used for breast cancer risk reduction in women at high risk, and as adjuvant treatment of axillary node-negative and node-positive, ductal carcinoma in situ. Tamoxifen treatment is also useful in the treatment of bone density and blood lipids in postmenopausal women. Adverse effects include hot flushes and more serious is two to three times higher relative risk of developing endometrial cancer compared to women of an age-matched population.
Toremifene, a chlorinated tamoxifen derivative, causes fewer DNA adducts in liver than seen with tamoxifen in preclinical studies and was developed to avoid hepatic carcinomas. It is used as endocrine therapy in women with ER/PR-positive stage 4 or recurrent metastatic breast cancer and has demonstrated similar efficacy compared to tamoxifen as adjuvant treatment of breast cancer and in the treatment of metastatic breast cancer.
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