Letrozole (brand name Femara) is an oral medication classified as a third-generation aromatase inhibitor. It blocks the aromatase enzyme, which is responsible for converting androgens into estrogen in the body. By significantly lowering estrogen levels, letrozole serves two primary medical purposes. It is used to starve hormone receptor-positive breast cancer cells, which rely on estrogen for growth, primarily in postmenopausal women. It is also used off-label to stimulate ovulation in women facing fertility challenges, such as those with Polycystic Ovary Syndrome (PCOS).
Starting Letrozole for Fertility Treatment Cycles
The timing for starting letrozole for fertility is precisely synchronized with the start of a woman’s menstrual cycle to maximize the medication’s effect on follicle development. Cycle Day 1 is the first full day of menstrual bleeding, and the tablets are typically started on Day 2, Day 3, Day 4, or Day 5. Starting the medication earlier in the cycle, such as on Day 2 or 3, may encourage the development of fewer, higher-quality follicles.
The standard protocol involves taking the medication once daily for a short, fixed duration, most commonly five consecutive days. This short course ensures that the temporary reduction in estrogen levels is timed perfectly to stimulate the pituitary gland to release more Follicle-Stimulating Hormone (FSH). The resulting surge in FSH acts directly on the ovaries to promote the growth and maturation of one or a few ovarian follicles.
The initial dosage is usually 2.5 milligrams (mg) once per day. If a patient does not ovulate on the initial dose, the prescribing physician may increase the dosage in subsequent cycles, typically in 2.5 mg increments, up to a maximum of 7.5 mg daily for five days. The goal of this careful dose titration is to induce the release of a single, mature egg, which helps to keep the risk of multiple pregnancies low.
The short half-life of the medication is a significant advantage in fertility treatment, as it ensures the drug is cleared from the body quickly after the five-day regimen is complete. This rapid clearance creates a more favorable hormonal environment for the uterine lining, or endometrium, important for successful embryo implantation. Ovulation usually occurs about five to twelve days after the final tablet is taken, requiring careful cycle monitoring for optimal timing of intercourse or an assisted procedure.
Starting Letrozole for Hormone Receptor-Positive Breast Cancer
When letrozole is prescribed for hormone receptor-positive breast cancer, the timing and duration of use are radically different from fertility treatment, as the goal is continuous estrogen suppression. The medication is typically taken as a standard dose of 2.5 mg once per day, and this use is not tied to the menstrual cycle. The drug is used almost exclusively in postmenopausal women, whose main source of estrogen is the peripheral conversion process that letrozole blocks.
Letrozole may be started in various phases of cancer treatment. In the adjuvant setting for early-stage cancer, it is started immediately following initial treatment like surgery. Patients typically take letrozole daily for a standard duration of five years. This long-term, continuous approach is designed to consistently deprive any remaining cancer cells of the estrogen they need to grow and reduce the risk of recurrence.
Another scenario is neoadjuvant therapy, where letrozole is started before surgery to shrink a tumor and potentially allow for a less invasive surgical procedure. In this case, the medication is taken daily for a defined period, which can range from three to twelve months, before the patient undergoes surgery. For advanced or metastatic cancer, letrozole is taken daily and continuously until the disease shows signs of progression.
Essential Preparations Before Taking the First Dose
Regardless of the medical indication, several preparatory steps are mandatory before a patient begins a letrozole regimen to ensure safety and effectiveness. For any woman who is premenopausal or of reproductive potential, a pregnancy test must be performed to confirm a negative result, as letrozole can pose a risk to a developing fetus. This confirmation is especially critical for fertility patients before each cycle of treatment.
A comprehensive physician consultation is necessary to review the patient’s full medical history and current medications to identify any potential drug interactions or contraindications. For breast cancer patients, confirming postmenopausal status is fundamental, as the drug’s mechanism is most effective when the ovaries are no longer producing estrogen. Even recently postmenopausal women may be advised to use contraception due to a small residual chance of pregnancy.
For patients undergoing fertility treatment, a baseline ultrasound is often required at the beginning of the cycle to confirm the absence of existing ovarian cysts before starting the medication. Specific baseline bloodwork is also drawn to assess hormone levels. These preparatory steps ensure the medication is initiated only when the patient is medically cleared and the timing is appropriate for the desired therapeutic outcome.