Aromatase inhibitors

Aromatase inhibitors

In postmenopausal women, estrogen is produced through aromatase, an enzyme that converts hormone precursors into estrogen. Aromatase inhibitors prevent androgen from being converted into estrogen in postmenopausal women, thereby blocking estrogen’s ability to activate can-cer cells; limiting the amount of estrogen means that less estrogen is available to reach cancer cells and make them grow.

Two types

There are two types of aromatase inhibitors. Type 1, or steroidal, inhibitors include exemestane; type 2, or nonsteroidal, inhibitors include anastrozole and letrozole.

Pharmacokinetics

Aromatase inhibitors are taken orally (in pill form) and are usually well tolerated. Steady-state plasma levels after daily doses are reached in 2 to 6 weeks. Inactive metabolites are excreted in urine.

Pharmacodynamics

Aromatase inhibitors work by lowering the body’s production of estrogen. In about one-half of all patients with breast cancer, the tumors depend on estrogen to grow. Aromatase inhibitors are used only in postmenopausal women because they lower the amount of estrogen that’s produced outside the ovaries, such as in muscle and fat tissue. Because these drugs induce estrogen depri-vation, bone thinning and osteoporosis may develop over time.

To reverse or not to reverse: That is the question

Type 1 inhibitors, such as exemestane, irreversibly inhibit the aro-matase enzyme, whereas type 2 inhibitors, such as anastrozole, re-versibly inhibit it. Type 1 aromatase inhibitors may still be effec-tive after a type 2 aromatase inhibitor has failed.

Competitive advantage

Anastrozale and letrozole work by competitively binding to heme of the cytochrome P450 subunit of aromatase, leading to de-creased levels of estrogen in all tissues; they don’t affect synthesis of adrenocorticosteroids, aldosterone, or thyroid hormones.

Pharmacotherapeutics

Aromatase inhibitors are primarily used to treat postmenopausal women with metastatic breast cancer. They may be administered alone or with other agents such as tamoxifen.

Drug interactions

Certain drugs may decrease the effectiveness of anastrozole, in-cluding tamoxifen and estrogen-containing drugs. (See Adversereactions to aromatase inhibitors.)