Description

Letrozole is a non-steroidal medication belonging to the class of drugs known as aromatase inhibitors. It is an oral medication primarily used in the treatment of breast cancer. Letrozole works by potently and selectively inhibiting the enzyme aromatase, which is responsible for estrogen synthesis. Because it does not affect the production of other steroids, it is a highly targeted hormonal therapy.

Indication

Letrozole is indicated for the treatment of hormone-dependent breast cancer in postmenopausal women. Its primary indications include:

• Adjuvant Treatment: As an initial adjuvant therapy for hormone receptor-positive early breast cancer.
• Extended Adjuvant Treatment: For postmenopausal women with early-stage breast cancer who have completed 5 years of tamoxifen therapy.

• Advanced Breast Cancer: For the treatment of advanced hormone receptor-positive or unknown primary breast cancer.
• Ovulation Induction (Off-label use): Letrozole is also used off-label in reproductive medicine to stimulate ovulation in women with ovulatory disorders (e.g., polycystic ovary syndrome, PCOS).

Mechanism of Action

The mechanism of action of letrozole is based on its ability to inhibit the synthesis of estrogen in the body.

1. Estrogen Production in Postmenopausal Women: In premenopausal women, the ovaries are the primary source of estrogen. However, after menopause, estrogen is produced primarily in peripheral tissues (such as fat, muscle, and liver) through the conversion of androgens (hormones like testosterone and androstenedione). This conversion is catalyzed by the enzyme aromatase.

2. Aromatase Inhibition: Letrozole acts as a potent and selective competitive inhibitor of the aromatase enzyme. It binds to the active site of the enzyme, blocking it from converting androgens into estrogens.

3. Significant Estrogen Reduction: By inhibiting aromatase, letrozole significantly reduces the levels of circulating estrogen in the body. This is a critical action because hormone-dependent breast cancer cells (those that are estrogen receptor-positive) require estrogen to grow and proliferate.

4. Anti-cancer Effect: The reduction in estrogen levels starves the cancer cells of the hormone they need to survive, leading to a decrease in tumor size or a delay in tumor progression.
5. Ovulation Induction (Off-label): When used for infertility, the mechanism is different. By reducing estrogen levels, letrozole removes the normal negative feedback on the hypothalamus and pituitary gland. In response, the hypothalamus increases the release of GnRH, which in turn stimulates the pituitary to secrete more follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The increased FSH stimulates the ovaries to develop mature follicles, leading to ovulation. This makes it an effective alternative to other ovulation-inducing drugs.