In a woman with WHO Group II anovulation (PCOS) who fails clomiphene citrate, the mechanism by which letrozole (aromatase inhibitor) achieves ovulation induction more effectively is:

• A Letrozole competitively occupies estrogen receptors in the hypothalamus permanently, preventing downregulation
• B Letrozole directly stimulates FSH secretion from pituitary gonadotrophs via LH receptor binding
• C Letrozole blocks peripheral aromatization of androgens to estrogen, reducing negative feedback on FSH with a normal pituitary response ✓
• D Letrozole induces endometrial VEGF expression, improving implantation rates

Explanation

Letrozole is a reversible aromatase inhibitor that blocks conversion of androgens to estrogens in the ovary and periphery. This reduces circulating estrogen levels, decreasing negative feedback on the hypothalamic-pituitary axis, causing a reflex rise in FSH that stimulates follicular recruitment. Unlike clomiphene (which depletes estrogen receptors causing endometrial thinning and hostile cervical mucus), letrozole's effect is transient — estrogen levels normalize after dominant follicle selection, preserving endometrial receptivity. LEGEND/PCOSACT trials confirmed letrozole superiority over clomiphene for live birth rates in PCOS.

Reference: Shaw's Textbook of Gynaecology, 17th ed.

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Written and medically reviewed by the StethoPrep medical team.