Raloxifene
Introduction
Raloxifene is a selective estrogen receptor modulator (SERM) primarily used for the prevention and treatment of osteoporosis in postmenopausal women. It mimics the beneficial effects of estrogen on bone density while blocking its undesirable effects on breast and uterine tissues. This dual action makes raloxifene an effective medication for maintaining bone health and reducing the risk of vertebral fractures without increasing the risk of breast or endometrial cancer.
Raloxifene is marketed under brand names such as Evista and is available in oral tablet form.
Mechanism of Action
Raloxifene acts by selectively binding to estrogen receptors (ERs) in different tissues, displaying both agonistic and antagonistic activities depending on the target site.
Agonist effect (mimics estrogen):
In bone tissue, it promotes osteoblast activity and reduces osteoclast-mediated bone resorption, maintaining bone mineral density (BMD).
Antagonist effect (blocks estrogen):
In breast and uterine tissues, it prevents estrogen-dependent cell proliferation, lowering the risk of hormone-driven cancers.
Thus, raloxifene provides the protective benefits of estrogen on bone without the carcinogenic risks associated with hormone replacement therapy (HRT).
Pharmacokinetics
Administration: Oral (typically 60 mg once daily)
Absorption: Moderately absorbed; bioavailability ≈ 2% due to extensive first-pass metabolism.
Metabolism: Primarily in the liver via glucuronidation (not CYP450 dependent).
Elimination: Excreted mainly in feces; half-life approximately 27–32 hours.
Therapeutic Uses
1. Osteoporosis Prevention and Treatment
Used in postmenopausal women to reduce the risk of vertebral fractures.
Improves bone mineral density (BMD), particularly in the spine and hips.
2. Reduction of Breast Cancer Risk
Lowers the incidence of invasive estrogen receptor-positive (ER⁺) breast cancer in postmenopausal women with osteoporosis or at high cancer risk.
3. Off-Label Uses
Investigated for lipid modulation (reducing LDL cholesterol).
Studied for cardiovascular protection and male osteoporosis, though not officially approved for these indications.