SERM

SERM stands for selective estrogen receptor modulator, a class of drugs that bind estrogen receptors and exhibit tissue-selective agonist or antagonist effects. They can block estrogen signaling in some tissues, notably breast tissue, while mimicking estrogen in others, such as bone or, in some cases, the endometrium.

Mechanism and action: Estrogen receptors are nuclear receptors that regulate gene transcription when bound by ligands. SERMs induce receptor conformations that recruit co-regulators differently across tissues, producing antiestrogenic effects in breast tissue and estrogenic effects in bone or uterus depending on the compound. This tissue selectivity underlies both therapeutic benefits and adverse effects.

Common agents and use: The class includes tamoxifen, raloxifene, toremifene, lasofoxifene, and bazedoxifene. Tamoxifen is a prodrug metabolized to active forms and is widely used for ER-positive breast cancer in pre- and postmenopausal women and for risk reduction in high-risk individuals. Raloxifene is used primarily to prevent osteoporosis in postmenopausal women and to reduce risk of invasive breast cancer in some high-risk patients; it tends to have lower endometrial risk than tamoxifen. Toremifene and lasofoxifene are used in select breast cancer or osteoporosis settings, with varying safety profiles. Bazedoxifene is used in combination therapies for menopausal symptoms and osteoporosis risk reduction in some regimens.

Clinical considerations: In breast cancer, SERMs can block estrogen-driven tumor growth and are used as adjuvant therapy or prevention in high-risk individuals. In osteoporosis, several SERMs promote bone density via estrogenic effects on bone. Safety concerns include thromboembolism risk for many SERMs; endometrial stimulation and cancer risk are concerns with tamoxifen, while raloxifene generally has a lower endometrial risk. Pharmacokinetics vary by agent; most are taken orally, and tamoxifen’s efficacy can be influenced by hepatic metabolism and interactions with CYP2D6 inhibitors.