Anastrozole is a nonsteroidal aromatase inhibitor. Anastrozole significantly suppresses serum estradiol levels, and it offers an alternative to tamoxifen in postmenopausal women with breast cancer. Anastrozole is highly potent and specific for aromatase, and represents the fourth generation of aromatase inhibitors. Unlike aminoglutethimide, an early aromatase inhibitor, anastrozole does not inhibit adrenal steroid synthesis.
Anastrozole has been tested for reducing estrogens, including estradiol, in men. Some athletes and body builders use anastrozole as part of their steroid cycle to reduce and prevent symptoms of excess estrogen–gynecomastia, emotional lability and water retention. Anastrozole causes less weight gain than megestrol and may offer a survival advantage over megestrol in women with advanced breast cancer. Anastrozole inhibits aromatase, the enzyme that catalyzes the final step in estrogen production.
Excess estradiol in men can cause benign prostatic hyperplasia, gynecomastia, and symptoms of hypogonadism. It can also contribute to increased risk of stroke, heart attack, chronic inflammation, prostate enlargement and prostate cancer.
Anastrozole is an oral, competitive, non-steroidal inhibitor of aromatase and is less likely to exhibit agonist or antagonist steroidal properties.
Study data suggest dosages of 0.5 mg to 1 mg a day reduce serum estradiol by approximately 50% in men, which differs in postmenopausal women.
Aromatase inhibitors are considered to be a standard of therapy and drug class of choice for the treatment of early breast cancer in postmenopausal women with hormone-receptor positive disease. The American Society of Clinical Oncology recommends that all postmenopausal women with hormone receptor-positive early breast cancer receive adjuvant aromatase inhibitor therapy.
The formation of adrenal corticosteroids or aldosterone is not affected by anastrozole; only serum estradiol concentrations are affected by anastrozole. In postmenopausal women, the principal source of circulating estrogens is from the conversion of adrenal and ovarian androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) by aromatase in peripheral tissues. Inhibition of aromatase may result in a more complete estrogen block than surgical ablation. Extraglandular sites are more amenable to aromatase inhibition by anastrozole than are premenopausal ovaries. Inhibiting the biosynthesis of estrogens is one way to deprive the tumor of estrogens and to restrict tumor growth. Estradiol plasma concentrations decrease about 80% from the baseline with continued dosing of anastrozole. Aromatase inhibitors might also inhibit estrogen production at the tumor cell. However, tumor production of estradiol may be insignificant because aromatase activity appears to be low. Anastrozole has little or no effect on CNS, autonomic, or neuromuscular function.