Paper II
2024 March (Supplementary) (2019 Scheme) · 100 marks · 180 min

Question

Classify the Selective Estrogen Receptor Modulators (SERMs) and explain the pharmacological basis of their clinical indications.

Q104 marksShort Answers

Answer

Classification of SERMs Tissue-selective drugs acting as estrogen agonists in some tissues and antagonists in others, depending on local receptor conformation and co-regulator proteins.

SERMTissue action
TamoxifenAntagonist — breast; Partial agonist — endometrium, bone
RaloxifeneAntagonist — breast, endometrium; Agonist — bone
ClomipheneAntagonist — hypothalamus

Pharmacological basis of clinical indications

  • Tamoxifen in ER-positive breast cancer — its antagonist action in breast tissue blocks estrogen-driven proliferative signaling in the tumour; its partial agonist effect on bone incidentally helps preserve bone density, but its endometrial agonist action raises endometrial cancer risk, requiring monitoring.
  • Raloxifene in postmenopausal osteoporosis — its bone-agonist action reduces osteoclast-mediated resorption like estrogen would, while its breast/endometrial antagonist action avoids the cancer risk traditional estrogen replacement carries.
  • Clomiphene in anovulatory infertility — blocking hypothalamic estrogen receptors removes negative feedback, increasing GnRH pulsatility and FSH/LH release, stimulating follicular development and ovulation.

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