1. SERMs Dr Sarvesh Singh Associate Professor

2. 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

3. 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

4. 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

5. 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

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

7. 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

8. 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

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

10. 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 )

11. 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

12. 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