Letrozole, known by the brand name Femara, is a non-steroidal aromatase inhibitor. Its core function involves blocking the enzyme aromatase, which is responsible for converting androgens into estrogens within the body. This action makes it a standard treatment for certain types of hormone receptor-positive breast cancer, where reducing estrogen levels helps slow tumor growth. The medication is also commonly used off-label in fertility treatment to induce ovulation in women experiencing difficulty conceiving. This dual use makes the question of its safety during a confirmed pregnancy particularly important.
Letrozole’s Role and Official Pregnancy Classification
Letrozole works by significantly lowering the concentration of estrogen circulating throughout the body’s tissues. For women who have gone through menopause, this suppression of estrogen production in peripheral tissues is the main mechanism for combating hormone-sensitive breast cancer. When used for fertility, this temporary estrogen reduction prompts the body to increase the release of follicle-stimulating hormones, thereby stimulating the ovaries to develop and release an egg.
Despite its use to initiate a pregnancy, Letrozole is strictly contraindicated for use once a pregnancy is confirmed. The U.S. Food and Drug Administration (FDA) labeling advises against its use in pregnant women, stating that based on animal studies and its mechanism of action, the drug can cause fetal harm. It is considered safe for fertility cycles because its short half-life ensures it is typically cleared from the body before the embryo implants and the critical period of organ development begins.
Specific Fetal Risks Associated with Exposure
The primary concern with Letrozole exposure during pregnancy stems from its potent anti-estrogen effects, which can severely disrupt the hormonal environment required for fetal development. Estrogen is necessary for the proper formation of numerous fetal structures, and its drastic reduction can lead to teratogenicity, meaning the potential to cause birth defects. Animal studies have provided strong evidence of adverse outcomes even at doses much lower than the recommended human therapeutic dose.
In pregnant rats and rabbits, exposure to Letrozole has been linked to increased rates of embryo and fetal death, as well as post-implantation pregnancy loss. The observed malformations in animal models included significant skeletal abnormalities, such as incomplete ossification of the skull, metatarsals, and sternebrae. Renal and urinary tract defects were also noted, including the absence or shortening of the renal papilla and dilation of the ureter. These data suggest that exposure during the first trimester, when major organs are forming, presents the highest risk of structural malformations.
Immediate Steps Upon Pregnancy Discovery
A patient who discovers they are pregnant while actively taking Letrozole must immediately stop the medication and contact their prescribing physician, oncologist, or fertility specialist. This immediate cessation is the single most important action to prevent further potential exposure to the developing embryo. The prescribing clinician will need to determine the specific timing and duration of the medication exposure relative to the early stages of the pregnancy.
The medical team will then initiate a plan for close monitoring, which may include specialized ultrasounds to assess fetal development and look for any signs of congenital anomalies. Women of childbearing potential are strongly advised to use effective, non-hormonal contraception consistently while on Letrozole and for a period of at least three weeks after the last dose, reflecting the drug’s clearance time.