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Letrozole: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on June 21, 2023.

1. How it works

  • Letrozole may be used to treat postmenopausal women whose cancers are fueled by hormones. It may also be used off-label for fertility issues.
  • Letrozole works by blocking the action of the enzyme aromatase, which prevents the body from converting androgens into estrogens. Estrogen is a hormone that causes some types of breast cancer to grow. Letrozole lowers the amount of estrogen in a woman's body.
  • Letrozole also induces ovulation in patients with polycystic ovary syndrome (PCOS), which is a condition where hormone imbalance can interfere with ovulation leading to anovulation (a lack of ovulation). It increases the chances of pregnancy in women who ovulate. Letrozole is also used to increase the chance of pregnancy in women who already ovulate. In these women, treatment with letrozole can result in the development of multiple follicles leading to multiple eggs being released. This process is known as controlled ovarian hyperstimulation or superovulation.
  • Letrozole belongs to the class of medicines known as aromatase inhibitors.

2. Upsides

  • Approved to treat postmenopausal women with hormone-receptor-positive early breast cancer, in addition to other treatments. Can also be given as extended treatment in postmenopausal women who have already received 5 years of adjuvant tamoxifen treatment.
  • May also be used to treat advanced-stage, hormone-receptor-positive, unknown locally advanced, or metastatic, breast cancer.Can also be given to postmenopausal women with advanced breast cancer with disease progression despite antiestrogen treatment.
  • When taken for breast cancer, letrozole is taken orally (by mouth) once a day or once every other day.
  • May be used off-label (as an unapproved use but recommended by the American College of Obstetricians and Gynecologists [ACOG] guidelines) for fertility issues in women with polycystic ovary syndrome (PCOS). When used for this purpose, letrozole is usually taken once a day for five days starting on day three or four of a woman's monthly cycle (the first day of your monthly cycle is the first day of your period) and then taken for five days.
  • No dosage adjustment is required for women with mild-to-moderate liver disease. The dose of letrozole in women with cirrhosis and severe liver disease should be reduced by 50%.
  • No dosage adjustment is required in people with kidney disease if their creatinine clearance is greater than or equal to 10 mL/min.
  • Available as a generic.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Common side effects include hot flashes and flushing, joint pain, weakness, fluid retention, fatigue, headache, dizziness, increased sweating, bone or muscle pain, nausea, weight decrease, and vaginal irritation.
  • Other reported side effects include bone effects (fractures, decreased bone mineral density, and osteoporosis) an increase in cholesterol levels, blood clots, stroke, heart attack, and endometrial cancer.
  • Treatment with letrozole is usually given for 5 years; however, women with a greater risk of disease recurrence may elect to continue therapy past 5 years, but side effects can be a concern.
  • Letrozole may cause hair thinning rather than total hair loss in approximately 3.4% to 6.2% of women taking letrozole. Most hair thinning or loss was not graded as a serious effect.
  • Letrozole can cause harm to a developing fetus and should not be taken by women who are already pregnant. When used for fertility issues, follow the guidance of your gynecologist. Women taking letrozole should not breastfeed during treatment and for at least 3 weeks following the last dose.
  • May decrease lymphocyte counts, but the significance of this is unknown and the effect was transient.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Letrozole is a treatment that may be used to reduce the risk of breast cancer recurrence in postmenopausal women and also to increase the chance of ovulation in women with polycystic ovary syndrome. Side effects include hot flashes, headaches, and joint pain, and it may lower bone mineral density and increase cholesterol levels.

5. Tips

  • Letrozole can be taken with or without food.
  • Report any worrying side effects, such as chest pain, leg pain, or cough to your doctor.
  • If you are taking letrozole to increase fertility, take it strictly as directed. Letrozole should not be taken once you have conceived. Talk to your doctor about this.
  • Letrozole is usually taken once a day or once every other day when used to treat or protect against breast cancer recurrence in postmenopausal women.
  • Be cautious when driving or operating machinery if letrozole makes you dizzy or tired.
  • Your doctor may wish to monitor your bone mineral density (BMD) while you are taking Letrozole as it may lower your BMD.

6. Response and effectiveness

  • Research has shown that treatment with aromatase inhibitors like letrozole can extend the length of time for a breast cancer recurrence or breast cancer spreading in the body. In one study, over 70% of women had a disease-free survival period of up to 8 years.
  • Studies that have compared tamoxifen with aromatase inhibitors (AIs) such as letrozole in early-stage breast cancer have shown that five years of treatment with AIs was more effective than tamoxifen at prolonging the time until breast cancer comes back or having breast cancer spread in the body.
  • There is also a benefit to switching to an AI after 2 or 3 years on tamoxifen or continuing an AI after 5 years of tamoxifen treatment (rather than stopping treatment altogether). However, there is no benefit to switching compared to using letrozole alone for 5 years; however, switching may be a reasonable option for patients who experience intolerable side effects with either drug.
  • Some women may benefit from extended therapy past 5 years based on the risk of disease recurrence, side effects, and previous treatments. The American Society of Clinical Oncology (ASCO) recommends that for women on extended letrozole treatment, 10 years should be the maximum duration of therapy.
  • Deciding to extend letrozole therapy should be a shared decision based on the risk of disease recurrence, drug side effects, disease status (node-positive/negative disease), and patient preference. A longer duration of letrozole use has been associated with increased bone fractures and heart side effects, as well as treatment discontinuation.
  • Treatment with letrozole should be discontinued if breast cancer returns.

7. Interactions

Medicines that interact with letrozole may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with letrozole. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with letrozole include:

  • antiandrogens, such as apalutamide
  • aprepitant
  • cannabidiol
  • cimetidine
  • citalopram
  • clobazam
  • clopidogrel
  • dabrafenib
  • echinacea
  • HIV medications, such as darunavir, efavirenz
  • hormones, such as estrone, ethinyl estradiol, or hydroxyprogesterone
  • ivacaftor
  • mifepristone
  • oxcarbazepine
  • St. John's Wort
  • tacrolimus or sirolimus
  • thalidomide
  • tamoxifen
  • warfarin.

Note that this list is not all-inclusive and includes only common medications that may interact with letrozole. You should refer to the prescribing information for letrozole for a complete list of interactions.


Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use letrozole only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2023 Revision date: June 21, 2023.