SERMs Dr Sarvesh Singh Associate Professor Email drsarveshsinghgmail

SERMs Dr Sarvesh Singh Associate Professor E-mail: drsarveshsingh@gmail. com

ESTROGEN RECEPTORS (ERS) • Demonstrated in female sex organs • Two types: • ERα: üPredominates in uterus, vagina, breast, hypothalamus and blood vessels • ERᵝ: üPredominates in prostate gland of males and ovaries in females

SERMs • Selective estrogen receptor modulators • Actions are in a tissue selective manner • Agents that act as: üEstrogen agonists in some tissues üAntagonists in other tissues • TWO SERMs: üRaloxifene üTamoxifen

RALOXIFENE • High affinity for both ERα and Erβ • Distinct DNA target the ‘raloxifene response element’ (RRE) • Partial agonistic actions in: üBone üCVS • Antagonistic actions in: üEndometrial üBreast

RALOXIFENE PARTIAL AGONISTIC ACTIONS IN: v Bone ü Prevents bone loss in postmenopausal women v CVS ü It reduces LDL cholesterol ANTAGONISTIC ACTIONS IN: v Endometrial ü No increase in the risk of endometrial carcinoma v Breast ü It reduces the risk of breast cancer

RALOXIFENE FIRST LINE DRUG FOR POSTMENOPAUSAL OSTEOPOROSIS ? BISPHONATE

RALOXIFENE BONE: • Bone mineral density (BMD) may increase by 0. 9– 3. 4% in different bones (particularly the lumbar vertebrae) • Risk of vertebral fracture is reduced to half, but not that of long bones • Ca 2+ and vit D supplements enhance the benefit • It is less efficacious than bisphonates in preventing fractures • Raloxifene is a second line drug for prevention and treatment of osteoporosis in postmenopausal women

RALOXIFENE • It reduces LDL cholesterol(by upregulating hepatic LDL receptors) • In contrast to estrogen HRT: üNo increase in HDL and triglyceride levels DISADVANTAGES: • No relief of menopausal vasomotor symptoms • Hot flushes may occur

RALOXIFENE SERIOUS DISADVANTAGE 3 -fold increase in risk of deep vein thrombosis and pulmonary embolism

TAMOXIFEN Estrogenic (agonist) action: ü Uterus (increased risk of endometrial carcinoma) ü Bone (Improvement in bone mass) Anti-estrogenic (antagonist) action – ü Breast (used for treatment of breast cancer) ü Blood (Improvement in lipid profile & increased risk of venous thromboembolism )

RALOXIFENE & TAMOXIFENE Similarities b/w Raloxifene & Tamoxifene üImprovement in lipid profile üIncreased risk of venous thromboembolism Differences b/w raloxifene & tamoxifene Raloxifene: üAntiestrogenic action on endometrium so NO RISK of carcinoma endometrium Tamoxifene: üEstrogenic action on endometrium so increased risk of carcinoma endometrium

TAKE HOME MESSAGES • Tamoxifen: used for treatment of breast cancer • Raloxifene: used for treatment of osteoporosis NOTE Increased risk of venous thromboembolism with BOTH