Tamoxifen

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Mechanism of action

• Competitive antagonist on the estrogen receptors of the breast → ↓ breast cancer cell growth
• Agonist on estrogen receptors in the following tissues:
  • Bone tissue → inhibition of osteoclasts → ↓ risk of osteoporosis and fractures
  • Endometrium → ↑ proliferation
  • Myometrium → ↑ proliferation

Indications

• Premenopausal estrogen receptor-positive breast cancer
• Vaginal atrophy (related to menopause)
• Prostate cancer: prevention of gynecomastia

Side effects

• Hot flashes
• ↑ Risk of endometrial cancer
• ↑ Risk of Uterine leiomyoma > Uterine leiomyosarcoma (uterine sarcoma)
• ↑ Risk of thromboembolic events (e.g., pulmonary embolism, DVT)
  • Proposed mechanisms include increased levels of clotting factors (eg, prothrombin; fibrinogen; factor VII, VIII, X) and activated protein C resistance.

Raloxifene

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Mechanism of action

• Competitive antagonist on estrogen receptors in the following tissues:
  • Breast → ↓ breast cancer cell growth
  • Endometrium and myometrium → ↓ proliferation (in contrast to tamoxifen)
• Agonist on estrogen receptor in bone tissue → inhibition of osteoclasts

Indications

• Prophylaxis of breast cancer in high-risk patients
• Osteoporosis in older patients (if bisphosphonates are contraindicated)

Side effects

• ↓ Risk of endometrial cancer and uterine sarcoma

Clomiphene

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Mechanism of action

• Blocks hypothalamic estrogen receptors, thereby inhibiting negative feedback and increasing release of FSH and LH to trigger ovulation

Indications

• Infertility (for ovulation induction)

Side effects