SERMs

Selective estrogen receptor modulators (SERMs) are a class of non-steroidal drugs that bind to estrogen receptors and exhibit tissue-selective agonist or antagonist activity. By interacting with estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), SERMs can mimic estrogen effects in some tissues while blocking estrogen action in others. This tissue specificity can help preserve bone density and improve lipid profiles while reducing estrogen-driven cell proliferation in different contexts.

Mechanism of action depends on tissue and receptor context. SERMs recruit different coactivators or corepressors in various tissues, leading to distinct patterns of gene expression. Some SERMs act as antagonists in breast tissue but as partial agonists or agonists in bone or vaginal tissue. Their effects are influenced by receptor subtype distribution, co-regulator levels, and metabolism to active metabolites such as endoxifen in the case of tamoxifen.

Clinical uses include cancer and bone health indications. Tamoxifen is used in the treatment of estrogen receptor–positive breast cancer and to reduce contralateral breast cancer risk in high-risk women. Raloxifene is approved for osteoporosis prevention and treatment in postmenopausal women and also reduces breast cancer risk in some high-risk populations, without increasing endometrial cancer risk. Other SERMs, such as clomiphene, are used for ovulation induction; newer agents like toremifene, bazedoxifene, lasofoxifene, and ospemifene have additional or specialized roles in osteoporosis, cancer risk reduction, or gynecologic symptom relief.

Adverse effects commonly include hot flashes, vaginal bleeding or discharge, and an increased risk of thromboembolism. Tamoxifen carries a known risk of endometrial changes; raloxifene has a lower endometrial risk. Drug metabolism via hepatic enzymes can affect individual response and interactions.