Selective Estrogen Receptor Modulators (SERMs)

Definition: SERMs are non-steroidal agents that bind the oestrogen receptor and act as tissue-selective agonists or antagonists — agonist on bone and lipids, antagonist on breast, with variable effect on the endometrium. Selectivity arises from differential recruitment of co-activators and co-repressors to ER-α and ER-β.

Agents: raloxifene (60 mg/day, second generation, the main bone agent), bazedoxifene (third generation, also used as a tissue-selective oestrogen complex with conjugated oestrogens), tamoxifen and toremifene (breast cancer), ospemifene (dyspareunia), lasofoxifene.

Mechanism on bone: agonist action suppresses osteoclastic resorption and reduces bone turnover, preserving BMD — a mild antiresorptive effect, weaker than bisphosphonates.

Indication in Pathy's algorithm: in postmenopausal women categorised as low fracture risk, menopausal hormone therapy and SERMs may be considered. Raloxifene raises lumbar spine BMD by about 3% and femoral neck by 2% at 12– 18 months and reduces vertebral fracture only.

Key limitation (frequently examined): raloxifene has not been found to decrease the incidence of femoral neck fractures, and SERMs must be avoided after femoral neck fracture because of the increased risk of thromboembolic complications.

Additional benefit: raloxifene reduces the incidence of ER-positive invasive breast cancer, making it attractive in a woman with vertebral osteoporosis and elevated breast cancer risk.

Adverse effects and cautions: venous thromboembolism (2–3 fold increase — the main hazard in the elderly and in the immobile), hot flushes, leg cramps, peripheral oedema; an excess of fatal stroke was seen in women with cardiovascular risk factors. Contraindicated in prior VTE, prolonged immobility, and active hepatic disease. Unlike oestrogen, raloxifene does not stimulate the endometrium (no increase in endometrial cancer) and does not relieve vasomotor symptoms.