IN POSTMENOPAUSAL WOMEN, ESTROGENS ARE MAINLY DERIVED FROM THE ACTION OF THE AROMATASE ENZYME, WHICH CONVERTS ADRENAL ANDROGENS (PRIMARILY ANDROSTENEDIONE AND TESTOSTERONE) TO ESTRONE AND ESTRADIOL. THE SUPPRESSION OF ESTROGEN BIOSYNTHESIS IN PERIPHERAL TISSUES AND IN THE CANCER TISSUE ITSELF CAN THEREFORE BE ACHIEVED BY SPECIFICALLY INHIBITING THE AROMATASE ENZYME.
LETROZOLE IS A NONSTEROIDAL COMPETITIVE INHIBITOR OF THE AROMATASE ENZYME SYSTEM; IT INHIBITS THE CONVERSION OF ANDROGENS TO ESTROGENS. IN ADULT NONTUMOR- AND TUMOR-BEARING FEMALE ANIMALS, LETROZOLE IS AS EFFECTIVE AS OVARIECTOMY IN REDUCING UTERINE WEIGHT, ELEVATING SERUM LH, AND CAUSING THE REGRESSION OF ESTROGEN-DEPENDENT TUMORS. IN CONTRAST TO OVARIECTOMY, TREATMENT WITH LETROZOLE DOES NOT LEAD TO AN INCREASE IN SERUM FSH. LETROZOLE SELECTIVELY INHIBITS GONADAL STEROIDOGENESIS BUT HAS NO SIGNIFICANT EFFECT ON ADRENAL MINERALOCORTICOID OR GLUCOCORTICOID SYNTHESIS.