Is Anastrozole an Aromatase Inhibitor?
Yes, anastrozole is definitively a third-generation nonsteroidal aromatase inhibitor that selectively blocks the aromatase enzyme to suppress estrogen production in postmenopausal women. 1
Mechanism of Action
Anastrozole functions as a selective non-steroidal aromatase inhibitor that specifically blocks the aromatase enzyme responsible for converting adrenal androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) in peripheral tissues. 1
- The drug binds reversibly to the heme group of the aromatase enzyme, distinguishing it from steroidal aromatase inhibitors like exemestane that bind irreversibly to the catalytic site. 2
- At the recommended 1 mg daily dose, anastrozole reduces estradiol by approximately 70% within 24 hours and by approximately 80% after 14 days of daily dosing, with suppression of mean serum concentrations to the lower limit of detection (3.7 pmol/L). 1
- The drug significantly lowers serum estradiol concentrations and has no detectable effect on formation of adrenal corticosteroids or aldosterone, demonstrating high selectivity for the aromatase enzyme. 1
Classification Among Aromatase Inhibitors
Anastrozole belongs to the nonsteroidal family of third-generation aromatase inhibitors, alongside letrozole, while exemestane represents the steroidal class. 3
- Third-generation aromatase inhibitors include two families: nonsteroidal inhibitors (anastrozole and letrozole) and steroidal inhibitors (exemestane). 3
- All three third-generation aromatase inhibitors (anastrozole, letrozole, exemestane) have shown similar anti-tumor efficacy and toxicity profiles in randomized studies in the adjuvant and preoperative settings. 3
Clinical Efficacy Evidence
Anastrozole has demonstrated superior efficacy compared to older endocrine agents and at least equivalent efficacy to tamoxifen in multiple clinical settings. 3
- As first-line treatment for postmenopausal patients with hormone receptor-positive metastatic breast cancer, anastrozole is recommended based upon a more favorable toxicity profile compared to tamoxifen, though tamoxifen remains a valuable option. 3
- Following tamoxifen failure, anastrozole showed superior efficacy compared to megestrol acetate and aminoglutethimide, with a significant survival advantage observed (median time to death 26.7 vs 22.5 months compared to megestrol). 4, 5
Critical Population Restriction
Anastrozole is only effective in postmenopausal women because aromatization of adrenal androgens is not a significant source of estradiol in premenopausal women. 2, 1
- In premenopausal women, anastrozole would not be expected to lower estradiol levels and must be combined with ovarian function suppression (LHRH agonists or surgical/radiotherapeutic ablation) if used at all. 3, 1
Common Pitfall to Avoid
The most critical error is attempting to use anastrozole as monotherapy in premenopausal women, where it will be ineffective without concurrent ovarian suppression, as the ovaries remain the primary source of estrogen production rather than peripheral aromatization. 3, 1