Letrozole

Letrozole is a prescription tablet that lowers oestrogen levels by blocking the aromatase enzyme. It is approved to treat hormone receptor-positive breast cancer in women after the menopause.

What it is

Letrozole is a tablet medicine from the group called aromatase inhibitors. It is sold under the brand name Femara and as generic versions ^[1]. It is used in the treatment of breast cancer in women who have been through the menopause ^[1]. It is a prescription-only medicine and is used under the care of a cancer specialist.

How it works

Letrozole is a non-steroidal, competitive inhibitor of the aromatase enzyme. It blocks the conversion of androgens into oestrogens, which lowers oestrogen production in postmenopausal women ^[1]. Its terminal elimination half-life is about 2 days, and steady levels in the blood are reached within 2 to 6 weeks ^[1]. Exposure to the drug is about doubled in people with liver cirrhosis ^[1].

Approved medical uses

• Adjuvant treatment of hormone receptor-positive early breast cancer in postmenopausal women ^[1].
• Extended adjuvant treatment of early breast cancer in postmenopausal women who have already completed tamoxifen treatment ^[1].
• Advanced breast cancer in postmenopausal women, as a first-line or second-line treatment ^[1].
• It is not approved for men ^[1].

What the research shows

• Bone health in breast cancer trials. In a trial summarised in the US label, bone mineral density fell by a median of 4.1% at 24 months with letrozole, compared with a small rise of 0.3% with tamoxifen ^[1]. After about 8 years of follow-up, fractures had occurred in 14.7% of women on letrozole and 11.4% of women on tamoxifen ^[1].
• Cholesterol. High cholesterol was reported in 52.3% of women taking letrozole and 28.6% of those taking tamoxifen, although severe cases were rare ^[1].
• Men with low testosterone or infertility. Aromatase inhibitors such as letrozole and anastrozole block the conversion of testosterone to oestrogen, and may counteract the way these hormones suppress the signals that drive the testes ^[2]. The American Urological Association (AUA) says clinicians may use aromatase inhibitors, selective oestrogen receptor modulators or hCG in men with testosterone deficiency who want to keep their fertility. This is a conditional recommendation based on lower-quality evidence, and it is an off-label use ^[3].
• Limits of the evidence in men. Reviewers describe these fertility approaches as not well established, limited in how widely they apply, and carrying side effects ^[2]. The bone and cholesterol findings above come from women with breast cancer ^[1].

Known risks and side effects

• Bone thinning and fractures: letrozole lowers bone mineral density, and fractures were more common than with tamoxifen in trials ^[1].
• Raised cholesterol is common ^[1].
• Tiredness, dizziness and sleepiness: caution is advised when driving or using machines ^[1].
• Liver disease: people with severe liver impairment have higher drug levels ^[1].
• Pregnancy: letrozole can cause miscarriage and birth defects. It must not be used in pregnancy, and women who could become pregnant need effective contraception during treatment and for 3 weeks after stopping ^[1].
• Common effects (in more than 20% of people in trials) include hot flushes, joint pain, flushing, weakness, fluid retention (oedema), headache, dizziness and muscle and bone pain ^[1].
• Sport: letrozole is prohibited at all times under the World Anti-Doping Agency (WADA) Prohibited List ^[4].

Blood tests commonly monitored

• Cholesterol (lipid profile): the label advises considering monitoring of serum cholesterol during treatment ^[1].
• Liver function: relevant because drug levels are higher in people with liver cirrhosis ^[1].
• Bone mineral density: not a blood test, but bone density monitoring should be considered during treatment ^[1].
• Oestradiol and testosterone: aromatase inhibitors act by changing the balance between these hormones, so they are the main measures discussed in reviews of their use in men ^[2]. There are no official monitoring guidelines for letrozole in men because it is not approved for use in men ^[1].

Sources

1. US Food and Drug Administration. Femara (letrozole) tablets prescribing information. FDA, 2017. accessdata.fda.gov
2. Herati AS, Kohn TP, Kassiri B. New frontiers in fertility preservation: a hypothesis on fertility optimization in men with hypergonadotrophic hypogonadism. Translational Andrology and Urology, 2020. PMC
3. American Urological Association (Mulhall, et al.). Evaluation and Management of Testosterone Deficiency: AUA Guideline. Journal of Urology and auanet.org, 2018 (validity confirmed 2024). auanet.org
4. World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. WADA, 2025. Prohibited List 2026 (PDF copy hosted by CONMEBOL)

Related

Last reviewed 7 October 2026. General information, not medical advice. Found a mistake? Email [email protected].