Letrozole

Third-generation non-steroidal aromatase inhibitor

ATC code: L02BG04

Brand names: Femara, Letrobel, Loxifan

Updated 24 Sep 2026 · Methodology

Indications

ER-positive breast cancer

First line

First-line adjuvant endocrine therapy for hormone-receptor positive breast cancer in postmenopausal women per ESMO 2024 and NCCN 2024. Dose 2.5 mg once daily for 5–10 years. The BIG 1–98 trial showed superiority over tamoxifen in disease-free survival. In metastatic ER+ HER2-negative disease, first-line combined with a CDK4/6 inhibitor (palbociclib, ribociclib, abemaciclib) or fulvestrant.

Postmenopausal women only. In premenopausal patients, concurrent ovarian function suppression is required.

Sources

ICD-10: C50 · ICD-11: 2C6Z

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Athletic endurance

Not recommended

Letrozole is used by amateur bodybuilders and AAS users as a more potent aromatase inhibitor. ASCO 2022 and the AEMPS Ficha Técnica confine letrozole to hormone-receptor-positive breast cancer. Approved indications in male athletes do not exist. Use causes marked bone mineral density loss, arthralgia, hypercholesterolemia, psychiatric effects and cardiovascular risk.

Sources

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

A selective reversible inhibitor of aromatase – the cytochrome P450 enzyme converting androgens (testosterone, androstenedione) to estrogens (estradiol, estrone) in peripheral tissues. In postmenopausal women, lowers plasma estradiol by 95–98%. Does not affect adrenal cortex or cortisol synthesis. Half-life 2 days; once-daily dosing.

Safety

Contraindications

Letrozole hypersensitivity
Premenopausal status without ovarian suppression
Pregnancy and lactation
Severe hepatic impairment

Serious adverse effects

Osteoporosis and fractures
Cardiovascular events (higher risk than with tamoxifen)
Hyperlipidemia
Thromboembolic events (less than with tamoxifen)
Hepatotoxicity

Common adverse effects

Hot flashes and night sweats
Joint and muscle pain
Fatigue
Nausea
Reduced libido and vaginal dryness
Weight gain

Pregnancy: can you take Letrozole?

Absolute contraindication. Teratogen. If pregnancy occurs on therapy, immediate discontinuation and obstetric consultation are required.

Breastfeeding: can you take Letrozole?

Contraindicated during lactation.

Calculate RID Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

Take once daily, with or without food. Standard adjuvant duration is 5 years; up to 10 years at high recurrence risk. Pre-treatment and 12-month DXA – osteoporosis and fracture risk. All patients on aromatase inhibitors receive calcium 1000–1200 mg and vitamin D 800–1000 IU/day; in osteoporosis or high risk, bisphosphonates or denosumab. Regular lipid profile monitoring.

Label mentions6 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

MajorTamoxifen
«No existe experiencia clínica hasta la fecha sobre el uso de letrozol en combinación con estrógenos u otros agentes anticancerosos, aparte de tamoxifeno. El tamoxifeno, otros antiestrógenos o…»
AEMPS, section 4.5 · Open on CIMA
ModerateClopidogrel
«In vitro, letrozol inhibe los isoenzimas 2A6 del citocromo P450 y, moderadamente, 2C19, pero se desconoce la relevancia clínica. Por tanto, se debe tener precaución cuando se administre de forma…»
AEMPS, section 4.5 · Open on CIMA
ModeratePhenytoin
«In vitro, letrozol inhibe los isoenzimas 2A6 del citocromo P450 y, moderadamente, 2C19, pero se desconoce la relevancia clínica. Por tanto, se debe tener precaución cuando se administre de forma…»
AEMPS, section 4.5 · Open on CIMA
Tamoxifen
«DRUG INTERACTIONS: Tamoxifen»
FDA, section 7 · Open on DailyMed
Warfarin
«DRUG INTERACTIONS: Warfarin»
FDA, section 7 · Open on DailyMed

From other drugs’ labels

ModerateTamoxifen
«Drug Interactions:: Tamoxifen reduced letrozole plasma concentrations by 37%. The effect of tamoxifen on metabolism and excretion of other antineoplastic drugs, such as cyclophosphamide and other…»
FDA, section 7 · Open on DailyMed

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Frequently asked

What is Letrozole used for?

Letrozole is evaluated for the following indications with varying evidence strength: ER-positive breast cancer (evidence tier A), Athletic endurance (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Letrozole?

Common side effects of Letrozole (≥ 1 in 100): Hot flashes and night sweats, Joint and muscle pain, Fatigue, Nausea, Reduced libido and vaginal dryness, Weight gain. See the Safety section for uncommon and serious reactions.

Is Letrozole safe during pregnancy?

Absolute contraindication. Teratogen. If pregnancy occurs on therapy, immediate discontinuation and obstetric consultation are required.

Is Letrozole compatible with breastfeeding?

Contraindicated during lactation.

Who should not take Letrozole?

Letrozole is contraindicated in: Letrozole hypersensitivity; Premenopausal status without ovarian suppression; Pregnancy and lactation; Severe hepatic impairment. Full list in the Safety section.

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMALabel dated 02/18/2026
FDA / DailyMedLabel dated 08/20/2026

Other drugs in this group

Abiraterone, Anastrozole, Bicalutamide, Exemestane, Tamoxifen