SERMs, SERDs & Tocolytics

Introduction & terminology

• SERM — Selective estrogen receptor modulators are compounds that act as estrogen agonists in some tissues and antagonists in others — tissue-selectively, not as uniform agonists/antagonists. The therapeutic goal: estrogenic benefit in bone, brain and liver while antagonising the breast and endometrium, where estrogen stimulation is deleterious.
• Receptor framework — Estrogen acts via two nuclear isoforms — ERα (ESR1), dominant in reproductive tract, breast and the driver of breast-cancer growth, and ERβ (ESR2), dominant in prostate/ovary, which can inhibit ERα transcription. A membrane GPER (GPR30) mediates rapid non-genomic effects.
• Keep the classes straight — SERM = mixed agonist/antagonist (tamoxifen, raloxifene, toremifene, ormeloxifene, bazedoxifene); antiestrogen / SERD = antagonist in all tissues — fulvestrant degrades the ER (clomiphene grouped here by G&G); aromatase inhibitor = blocks estrogen synthesis, not an ER ligand at all.