Letrozole, known commercially as Femara, is a potent oral medication classified as a non-steroidal aromatase inhibitor. Its core function involves blocking the enzyme aromatase, which converts androgens into estrogens in the body’s peripheral tissues. By inhibiting this process, the drug effectively lowers overall circulating estrogen levels. This mechanism is fundamental to its therapeutic uses but creates a significant safety concern regarding its use during pregnancy.
Primary Uses of Letrozole
The primary application of letrozole, for which it received initial regulatory approval, is the treatment of hormone-receptor-positive breast cancer in postmenopausal women. For these patients, estrogen acts as a fuel for cancer growth, and the drug’s ability to suppress estrogen production helps to slow or stop the progression and recurrence of the disease. It is often prescribed as an adjuvant treatment following initial therapies like surgery or radiation, or for advanced-stage cancer.
Beyond oncology, letrozole is also used widely in reproductive medicine, though this is considered an off-label use. It serves as a first-line agent for inducing ovulation, particularly in women dealing with infertility related to conditions such as Polycystic Ovary Syndrome (PCOS). The transient reduction in estrogen triggers a release of follicle-stimulating hormone (FSH) from the brain, which in turn stimulates the ovaries to mature and release an egg.
Fetal Risks Associated with Letrozole Exposure
Letrozole is formally contraindicated for use in women who are pregnant. The drug’s mechanism of action, which involves profoundly suppressing estrogen, is the direct cause of this concern. Estrogen is a naturally occurring hormone that plays an indispensable role in promoting healthy intrauterine growth and the development of numerous fetal organ systems.
Continuous exposure during pregnancy can drastically reduce the estrogen required for proper fetal development. Animal studies have demonstrated that letrozole exposure can lead to increased embryo and fetal toxicity, resulting in higher rates of pregnancy loss. The data also suggests a risk of congenital malformations, including skeletal defects and genital abnormalities, particularly if exposure occurs during the crucial early stages of organ formation.
Post-marketing surveillance in humans, although limited, has reported cases of spontaneous abortions and specific congenital birth defects following exposure to the medication. Due to the clear potential for harm, the drug’s manufacturer advises against its use during gestation. Letrozole was previously classified as Pregnancy Category D, a designation indicating evidence of human fetal risk.
Medical Guidance for Planning Pregnancy
For any woman of reproductive age who is taking letrozole, the absolute necessity of effective contraception cannot be overstated. This precaution must be maintained throughout the entire course of treatment to prevent accidental fetal exposure. Consulting with a specialist regarding reliable birth control options is a required part of the treatment plan.
The need for contraception extends beyond the final dose of the medication due to the time it takes for the drug to clear the body. Letrozole has a terminal elimination half-life of approximately 40 to 48 hours. To ensure the drug is nearly eliminated from the bloodstream, women are advised to continue using effective contraception for at least three weeks after taking their last letrozole tablet.
If a patient discovers she is pregnant while undergoing letrozole treatment, the immediate and most important step is to stop taking the medication and contact her healthcare provider without delay. Pre-conception counseling is strongly recommended for women who are using the drug for fertility or who are breast cancer survivors considering future pregnancy. This counseling allows for a thorough assessment of risks and the creation of a plan to minimize fetal exposure before attempting conception.