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

ESTROGEN RECEPTORS (ERS) Demonstrated in female sex organs Two types: ERα: Predominates in uterus, vagina, breast, hypothalamus and blood vessels ERᵝ: Predominates 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: Estrogen agonists in some tissues Antagonists in other tissues TWO SERMs: Raloxifene Tamoxifen

RALOXIFENE High affinity for both ERα and Erβ Distinct DNA target the ‘raloxifene response element’ (RRE) Partial agonistic actions in: Bone CVS Antagonistic actions in: Endometrial Breast

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

FIRST LINE DRUG FOR POSTMENOPAUSAL OSTEOPOROSIS RALOXIFENE FIRST LINE DRUG FOR POSTMENOPAUSAL OSTEOPOROSIS ? BISPHOSPHONATE

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 Ca2+ and vit D supplements enhance the benefit It is less efficacious than bisphosphonates 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: No 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: Uterus (increased risk of endometrial carcinoma) Bone (Improvement in bone mass) Anti-estrogenic (antagonist) action – Breast (used for treatment of breast cancer) Blood (Improvement in lipid profile & increased risk of venous thromboembolism )

RALOXIFENE & TAMOXIFENE Similarities b/w Raloxifene & Tamoxifene Improvement in lipid profile Increased risk of venous thromboembolism Differences b/w raloxifene & tamoxifene Raloxifene: Antiestrogenic action on endometrium so NO RISK of carcinoma endometrium Tamoxifene: Estrogenic action on endometrium so increased risk of carcinoma endometrium

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