medicationPrescription only (US)Used off-label for ovulation induction in the cited trial; FDA-approved indication is breast cancer
LetrozoleBenefits, Dosage & Interactions
Also known as: Femara
Letrozole, marketed under the brand name Femara, is an oral medication categorized as a non-steroidal aromatase inhibitor. It is predominantly used in the treatment of hormone-receptor-positive breast cancer in postmenopausal women. The reported plasma half-life is about 48 hours, which shapes dosing frequency.
How much Letrozole do people take?
The cited randomized trial used letrozole 2.5 mg once daily for 5 days, increased to 5 mg or 7.5 mg in later cycles without ovulation, for up to 5 cycles. Route reported: Oral. Frequency reported: Once daily for 5 days per cycle in the cited trial. These are amounts documented in the cited studies and labels for Letrozole — they are reported for reference, not a recommendation. Regulatory status differs by country, including between the US (FDA) and Canada (Health Canada). Confirm any amount with a licensed clinician before you take it.
See the full reported protocol and its sourcesResearched by DoseRoutine Research TeamReviewed for accuracy by Nicholas Alexander, RSE, SO, PMPLast updated Educational reference only — not medical advice. Always confirm dosing and safety decisions with a licensed clinician.
Evidence: Moderate — One published human randomized trial; results not yet replicated.
Evidence strengthModerate · 3/4
PreclinicalStrong human evidence
One published human randomized trial; results not yet replicated.
Plasma half-life
2–4 days
Default unit
mg
What published protocols report
Ranges documented in the literature, shown for reference. DoseRoutine does not recommend an amount — your prescriber or the product label sets the dose.
- Reported amounts
- The cited randomized trial used letrozole 2.5 mg once daily for 5 days, increased to 5 mg or 7.5 mg in later cycles without ovulation, for up to 5 cycles[1]
- Route studied
- Oral[1]
- Frequency
- Once daily for 5 days per cycle in the cited trial[1]
- Cycle length
- Up to 5 treatment cycles in the cited trial[1]
- Half-life
- Roughly 2 days[1]
- Storage
- Room temperature, sealed[1]
Reported for Letrozole in the cited sources. Published ranges are not dosing advice.
References & evidence
Documents the Letrozole entry is written from. Each number matches an inline marker above.
- [1]Letrozole versus clomiphene for infertility in the polycystic ovary syndromeLegro RS, Brzyski RG, Diamond MP, et al. · The New England Journal of Medicine · 2014 · Peer-reviewed · PMID 25006718
References & Evidence
Sources on this page that document Letrozole dosing, timing and safety.
- [1]U.S. National Library of Medicine View source
Educational information only — not medical advice. Dose ranges vary by person, indication and prescriber.
What is Letrozole?Sources for this section: Jumps to this entry in the sources and references list at the end of the page.
Letrozole, marketed under the brand name Femara, is an oral medication categorized as a non-steroidal aromatase inhibitor. It is predominantly used in the treatment of hormone-receptor-positive breast cancer in postmenopausal women. By inhibiting the enzyme aromatase, letrozole significantly reduces the production of estrogen in the body. While its primary role is in oncology, it has also been used off-label in certain fertility treatments and conditions where estrogen reduction is beneficial. Its high efficacy in reducing estrogen levels makes it a valuable tool in managing estrogen-dependent cancers and conditions where excessive estrogen may be detrimental.
What does the research say about Letrozole?
Tap a section to expand.
Letrozole exerts its therapeutic effects by selectively inhibiting the enzyme aromatase. Aromatase is a cytochrome P450 enzyme responsible for a crucial step in the biosynthesis of estrogens (estrone and estradiol) from androgenic precursors (androstenedione and testosterone) in various tissues, including adipose tissue, liver, muscle, and breast tissue. In postmenopausal women, the ovaries cease to produce significant amounts of estrogen, and estrogen production primarily occurs in peripheral tissues via the aromatase enzyme. By binding competitively to the heme component of the aromatase enzyme, letrozole blocks its activity, thereby reducing systemic estrogen levels. This reduction in estrogen is particularly beneficial in hormone-receptor-positive breast cancers, as the growth of these cancers is often stimulated by estrogen. The FDA label for Letrozole details this mechanism of action.
Source for this section: Sources for How does Letrozole work?: Jumps to this entry in the sources and references list at the end of the page.
The primary approved benefit of letrozole is in the treatment of hormone-receptor-positive breast cancer in postmenopausal women. This includes:
* **Adjuvant treatment:** For early-stage breast cancer after initial surgery, to reduce the risk of recurrence.
* **Extended adjuvant treatment:** For patients who have completed 5 years of adjuvant tamoxifen therapy, to further reduce recurrence risk.
* **First-line treatment:** For advanced breast cancer.
* **Second-line treatment:** For advanced breast cancer that has progressed after antiestrogen therapy.
Beyond its primary use in oncology, letrozole has also been investigated and used off-label for other conditions. In fertility treatment, particularly for women with polycystic ovary syndrome (PCOS), it may be used to induce ovulation due to its ability to lower estrogen, which can lead to an increase in follicle-stimulating hormone (FSH). However, this is an off-label use and should only be considered under strict medical supervision. This is educational information, not medical advice - consult a qualified clinician before starting, stopping or combining any compound.
Numerous large-scale clinical trials have established the efficacy of letrozole in breast cancer treatment. For example, the BIG 1-98 trial, a landmark study, compared letrozole to tamoxifen and found that letrozole was superior in reducing the risk of recurrence in postmenopausal women with hormone-receptor-positive early breast cancer. Another significant trial, presented by the National Cancer Institute, showed that extended adjuvant therapy with letrozole significantly improved disease-free survival compared to placebo after 5 years of tamoxifen. The Cochrane Library contains systematic reviews that corroborate these findings, emphasizing the role of aromatase inhibitors like letrozole in improving outcomes for breast cancer patients. Evidence for off-label uses, such as for ovulation induction in PCOS, also exists in clinical studies published in journals like Fertility and Sterility, demonstrating its effectiveness in this context, although it is not an FDA-approved indication for letrozole. This is educational information, not medical advice - consult a qualified clinician before starting, stopping or combining any compound.
As letrozole works by significantly reducing estrogen levels, many of its side effects are related to estrogen deficiency. Common side effects, as reported in the FDA label and MedlinePlus, include:
* Hot flashes
* Joint pain (arthralgia)
* Muscle pain (myalgia)
* Fatigue
* Nausea
* Headache
* Bone thinning (osteoporosis) leading to increased fracture risk
* Night sweats
* Hair thinning
* High cholesterol levels
* Weight gain
Less common but more serious side effects can include:
* Thromboembolic events (blood clots)
* Cardiovascular issues (e.g., angina, myocardial infarction)
* Stroke
* Liver enzyme elevations
Patients should report any new or worsening symptoms to their healthcare provider. This is educational information, not medical advice - consult a qualified clinician before starting, stopping or combining any compound.
Source for this section: Sources for What are the side effects of Letrozole?: Jumps to this entry in the sources and references list at the end of the page.
Letrozole should be used with caution in certain populations and conditions. Due to its impact on estrogen levels, it can lead to a decrease in bone mineral density and an increased risk of osteoporosis and fractures. Bone density monitoring is often recommended during treatment. Patients with a history of cardiovascular disease or risk factors should be closely monitored, as cardiovascular events have been reported. Liver function should be assessed before and periodically during treatment, especially in patients with pre-existing hepatic impairment. Pregnant women and women of childbearing potential should not use letrozole due to the potential for fetal harm; effective contraception should be used if there is any chance of becoming pregnant. The FDA label provides detailed warnings and precautions. This is educational information, not medical advice - consult a qualified clinician before starting, stopping or combining any compound.
Source for this section: Sources for Who should avoid Letrozole?: Jumps to this entry in the sources and references list at the end of the page.
Letrozole is contraindicated in individuals with known hypersensitivity to the active substance or to any of the excipients. It is also contraindicated in pregnant or potentially pregnant women, as it can cause fetal harm. In premenopausal women, letrozole is generally not indicated for breast cancer treatment, as ovarian function is intact and estrogen suppression mechanisms differ. For specific contraindications related to liver impairment or other severe medical conditions, consult the FDA label or a medical professional. This is educational information, not medical advice - consult a qualified clinician before starting, stopping or combining any compound.
Source for this section: Sources for When should Letrozole not be taken?: Jumps to this entry in the sources and references list at the end of the page.
Letrozole should be used with caution, or avoided, in combination with certain medications or substances. The primary concern relates to drugs that may interact with its metabolism or counteract its estrogen-lowering effects.
* **Tamoxifen and other anti-estrogens:** Co-administration with tamoxifen can reduce the plasma concentration of letrozole and should generally be avoided as it may diminish letrozole's efficacy. The FDA label advises against concurrent use.
* **Estrogen-containing medications:** Any medications or supplements containing estrogen (e.g., hormone replacement therapy, some oral contraceptives) will counteract the effects of letrozole and render it ineffective. These should be strictly avoided.
* **CYP3A4 inhibitors/inducers:** Letrozole is metabolized primarily by CYP2A6 and partially by CYP3A4. Strong inhibitors of CYP3A4 (e.g., ketoconazole, ritonavir) or inducers (e.g., rifampicin, St. John's Wort) could potentially alter letrozole concentrations, although clinical significance is often considered minimal for CYP3A4-mediated interactions according to the EMA SmPC. Nevertheless, caution is advised.
* **Coumarin-type anticoagulants:** Close monitoring of prothrombin time is recommended if letrozole is co-administered with coumarin-type anticoagulants due to potential interaction, as noted in the EMA SmPC.
Always discuss all medications, supplements, and herbal remedies with a healthcare provider before combining them with letrozole. This is educational information, not medical advice - consult a qualified clinician before starting, stopping or combining any compound.
Source for this section: Sources for What should you not mix with Letrozole?: Jumps to this entry in the sources and references list at the end of the page.
Letrozole is typically taken once daily. The specific dose and duration of treatment are user-directed and must be set by a licensed clinician based on the individual's medical condition, the type of cancer, and response to therapy. It can be taken with or without food. Consistent daily timing is often recommended to maintain stable drug levels. For adjuvant treatment, therapy may extend for several years (e.g., 5 to 10 years). In advanced settings, treatment continues until disease progression or unacceptable toxicity. Always follow the precise instructions provided by your prescribing clinician.
Put it into practice
Reading about Letrozole is the first step — DoseRoutine helps you act on it. These free tools turn what you just learned into a routine.
What interacts with Letrozole?
Frequently asked questions about Letrozole
Letrozole is primarily used to treat hormone-receptor-positive breast cancer in postmenopausal women.
Letrozole works by inhibiting the enzyme aromatase, which is responsible for producing estrogen in the body. By lowering estrogen levels, it helps to slow or stop the growth of estrogen-sensitive breast cancers.
While letrozole's primary use is in postmenopausal women, it has been used off-label in men for conditions like gynecomastia or to manage estrogen levels, particularly in certain bodybuilding contexts or fertility treatments, under strict medical supervision.
Common side effects often mimic menopausal symptoms due to reduced estrogen and include hot flashes, joint pain, fatigue, and night sweats. More serious side effects like bone thinning or cardiovascular issues can occur.
No, letrozole is not a traditional chemotherapy drug. It is a type of hormone therapy or endocrine therapy that works by targeting hormones that fuel cancer growth, rather than directly killing fast-growing cells throughout the body.
As a medication, Letrozole can overlap with other supplements, prescription medicines, hormones and peptides. With a reported plasma half-life near 48 hours, separating doses can change the picture as much as removing one. Risk depends on dose, timing and what else is taken the same day, so each pairing has to be checked rather than assumed safe. The free checker at https://doseroutine.com/interaction-checker covers Letrozole with no sign-up.
The reported plasma half-life is about 48 hours, which is what drives how often it is redosed. Amounts for this medication vary by protocol, formulation and individual response, so follow the dose your clinician or the product label specifies.
Whether Letrozole fits alongside testosterone replacement therapy depends on the protocol — dose, ester and ancillaries such as HCG or anastrozole — and on current bloodwork. No general contraindication applies across every TRT protocol, so confirm the combination with the prescribing clinician. See the free TRT interaction reference: https://doseroutine.com/trt-supplement-interactions
"Peptides" is not one category — healing peptides, GLP-1 agonists, growth-hormone secretagogues and melanocortins each behave differently next to Letrozole. Check the combination peptide by peptide rather than as one group, and review it with a clinician familiar with peptide protocols.
A long plasma half-life of about 48 hours means Letrozole is commonly dosed every few days or weekly rather than daily. Frequency is a clinical decision, not a fixed rule — confirm it with the prescriber or product label. Comparison of apps that keep a schedule like this: https://doseroutine.com/best-dose-tracking-apps
With a plasma half-life near 48 hours, a single missed dose of Letrozole usually has a smaller effect on overall exposure than an irregular pattern of missed doses does. Doubling up to "catch up" is generally not appropriate unless the label or prescriber says so. Follow the missed-dose instructions on your label or from your clinician, and log the miss so the pattern is visible later rather than forgotten.
For Letrozole the useful record is the dose, the time it was actually taken, and what else was taken in the same window. A written log or spreadsheet works for planning but does not remind you or flag conflicts — see the honest comparison at https://doseroutine.com/vs/spreadsheet and the wider roundup at https://doseroutine.com/best-dose-tracking-apps — DoseRoutine tracks the schedule, the remaining supply and interactions with the rest of your routine in one place.
The cited randomized trial used letrozole 2.5 mg once daily for 5 days, increased to 5 mg or 7.5 mg in later cycles without ovulation, for up to 5 cycles. Route reported: Oral. Frequency reported: Once daily for 5 days per cycle in the cited trial. These are amounts documented in the cited studies and labels for Letrozole — they are reported for reference, not a recommendation. Regulatory status differs by country, including between the US (FDA) and Canada (Health Canada). Confirm any amount with a licensed clinician before you take it.
Which studies looked at Letrozole?
Peer-reviewed research indexed in PubMed. Each entry links to the original record.
- 1.Palbociclib and Letrozole in Advanced Breast Cancer(opens PubMed in a new tab)N Engl J Med · 2016 · PMID 27959613 · https://pubmed.ncbi.nlm.nih.gov/27959613/
- 2.Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer(opens PubMed in a new tab)Ann Oncol · 2018 · PMID 29718092 · https://pubmed.ncbi.nlm.nih.gov/29718092/
- 3.Letrozole for Female Infertility(opens PubMed in a new tab)Front Endocrinol (Lausanne) · 2021 · PMID 34220713 · https://pubmed.ncbi.nlm.nih.gov/34220713/
- 4.Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer(opens PubMed in a new tab)N Engl J Med · 2022 · PMID 35263519 · https://pubmed.ncbi.nlm.nih.gov/35263519/
Sources cited on this page
Specific documents referenced by the numbered markers above. Each number matches the marker in the text.
- MedlinePlus(opens in a new tab)U.S. National Library of Medicine · medlineplus.gov/druginfo/meds/a698004.html
Verify at
Publisher search links for Letrozole. These are places to check the information — they are not citations, so they are not numbered.
- FDA-approved labeling (DailyMed)(publisher search, opens in a new tab)U.S. Food and Drug Administration · publisher search
- PubChem(publisher search, opens in a new tab)National Center for Biotechnology Information · publisher search
- Cochrane Library(publisher search, opens in a new tab)Cochrane · publisher search
- DrugBank(publisher search, opens in a new tab)DrugBank Online · publisher search
- PubMed literature search(publisher search, opens in a new tab)National Library of Medicine · publisher search
- Wikipedia entry(publisher search, opens in a new tab)Wikipedia · publisher search
DoseRoutine compiles summaries from publicly available scientific and regulatory references. Always verify important decisions with a licensed clinician. How we source and review this information.
What is the short answer on Letrozole?
Plain-text summary, safe to quote verbatim:
Letrozole, marketed under the brand name Femara, is an oral medication categorized as a non-steroidal aromatase inhibitor. It is predominantly used in the treatment of hormone-receptor-positive breast cancer in postmenopausal women. The reported plasma half-life is about 48 hours, which shapes dosing frequency.
Source: DoseRoutine — https://doseroutine.com/library/letrozole
Letrozole cheat sheet
DoseRoutine cheat sheet · Medication
Letrozole
Letrozole, marketed under the brand name Femara, is an oral medication categorized as a non-steroidal aromatase inhibitor. It is predominantly used in the treatment of hormone-receptor-positive breast cancer in postmenopausal women.
Evidence
Moderate
One published human randomized trial; results not yet replicated.
Studied range
The cited randomized trial used letrozole 2.5 mg once daily for 5 days, increased to 5 mg or 7.5 mg in later cycles without ovulation, for up to 5 cycles
Route
Oral
Frequency studied
Once daily for 5 days per cycle in the cited trial
Half-life
2–4 days
Storage
Room temperature, sealed
Prescription only (US)Used off-label for ovulation induction in the cited trial; FDA-approved indication is breast cancer
Key references
Studied ranges, not dosing advice. Not medical advice — talk to a clinician. doseroutine.com/library/letrozole
Cite this page
Using this in an article, AI answer, or research note? Please attribute:
DoseRoutine. (2026). Letrozole — Overview, Benefits & Side Effects. Retrieved from https://doseroutine.com/library/letrozole
What compounds are similar to Letrozole?
Others in the medication category or studied for the same goals.