7 Possible Side Effects of Letrozole and How to Manage Them

Letrozole (Femara) is a medication that treats certain types of estrogen-sensitive breast cancer. It’s most often used if you’ve gone through menopause and have already received other breast cancer treatments, such as surgery or radiation. Letrozole is also used off-label for certain types of infertility.

Whether you’ve been prescribed letrozole for breast cancer or infertility, you may be wondering about what side effects to expect. Here, we’ll dive deeper into seven letrozole side effects you should know about. This list doesn’t include all possible side effects, so be sure to reach out to your healthcare provider if you have questions or concerns.

1. High cholesterol

The most common side effect of letrozole is high cholesterol. In clinical trials, more than half of people taking it experienced increased cholesterol levels. And about 30% of people taking letrozole needed to take cholesterol medication because of this side effect.

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Over time, high cholesterol levels can raise your risk of serious complications, such as a heart attack or stroke. Especially if they’re left untreated.

Your healthcare provider will likely check your cholesterol levels before and during treatment with letrozole. A healthy diet and exercise can help lower your cholesterol. If these aren’t enough, your healthcare provider may prescribe a medication to lower your cholesterol.

2. Hot flashes and night sweats

Letrozole blocks an enzyme (protein) called aromatase. This enzyme changes androgen hormones (like testosterone) found in skin, muscle, and fat cells into estrogen. So blocking it lowers estrogen levels in the body.

Low estrogen levels tend to cause hot flashes. About 30% of people reported hot flashes when taking letrozole for breast cancer. In studies of letrozole for PCOS-related infertility, about 20% reported this side effect. Like hot flashes, night sweats can also happen when estrogen levels are low. Almost 15% of people taking letrozole for breast cancer in clinical trials reported this side effect.

Hot flashes and night sweats may be annoying, but they’re not dangerous. Lifestyle changes — like exercising and eating more fruits and veggies — may help. Some people find that mindfulness practices, such as yoga and meditation, are also useful.

There are some natural supplements available over the counter (OTC) to treat hot flashes, but these aren’t recommended if you’re taking letrozole. Some of these products contain plant-based estrogens, known as phytoestrogens. Phytoestrogens act like estrogen in the body. So while they might improve hot flashes, they could interfere with how letrozole works.

3. Fatigue

Fatigue was felt by almost 10% of people taking letrozole for breast cancer. When used for infertility, about 22% of people reported feeling tired.

If fatigue happens while you’re using letrozole, try taking your dose at night. Use caution when driving or operating machinery until you know how letrozole affects you. If this letrozole side effect becomes too bothersome, speak with your healthcare provider.

4. Nausea

Nausea is a common side effect of many medications, including letrozole. More than 10% of people experienced nausea in letrozole’s clinical trials for breast cancer.

Letrozole can be taken with or without food. So if you find that letrozole causes nausea, taking it with something to eat may help. It’s also a good idea to stay hydrated and eat smaller, more frequent meals. These steps can help manage nausea caused by letrozole.

5. Weight changes

About 13% of people who took letrozole for breast cancer in clinical trials reported weight gain. Around 6% experienced weight loss. It’s not mentioned how much weight people gained or lost during these studies.

By taking proactive steps, like healthy eating and regular exercise, you may be able to prevent or manage weight gain from letrozole. There are healthy ways to manage unwanted weight loss, too. Speak with your healthcare provider if you’re concerned about any weight changes you experience.

6. Muscle and joint pain

Muscle and joint pain is the most common reason people decide to stop taking letrozole. This side effect is sometimes called aromatase-inhibitor associated arthralgia.

More than 25% of people reported joint pain in letrozole’s clinical trials. About 10% of people had muscle pain. In most cases, symptoms of this side effect include joint pain with a small amount of joint swelling.

Estrogen is important for bone health. Without it, bone loss often happens (more about this next). This bone loss may cause joint pain. Estrogen may also play a role in how the nerves perceive pain.

If you have joint pain while taking letrozole, an OTC medication, such as ibuprofen (Advil, Motrin) or naproxen (Aleve), may help. Just make sure it’s OK with your healthcare provider first.

7. Bone loss and fractures

As mentioned above, low estrogen levels can lead to bone loss. Because letrozole lowers estrogen levels, it can cause bone loss as a side effect. Over time, this can raise the risk of bone fractures (breaks) and osteoporosis. In fact, bone fractures occurred in almost 15% of people taking letrozole for breast cancer during clinical trials.

A scan to check the strength of your bones is typically recommended before starting and while taking letrozole. Your healthcare provider may also recommend taking calcium with vitamin D or a medication called Prolia (denosumab) to strengthen your bones while you’re taking letrozole.

When should I contact my healthcare provider about letrozole side effects?

Common letrozole side effects can be frustrating, but they’re usually not serious. And most side effects tend to go away once letrozole is stopped. However, if any letrozole side effects become too bothersome, talk to your healthcare provider about other options. Don’t stop taking letrozole on your own.

Serious letrozole side effects are rare, but they can happen. Call 911 or seek emergency medical care if you notice symptoms of a serious side effect, such as:

• Bone fractures. Sudden pain, swelling, or trouble moving a limb may be signs of a bone fracture.

• Heart attack. Symptoms of a heart attack include chest pain or pressure that’s worse during exertion. Other symptoms may include shortness of breath, sweating, or indigestion.

• Stroke. Symptoms of a stroke can include weakness on one side of the body, facial changes, or difficulty speaking.

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Written by:

Nicole E. Cieri-Hutcherson, PharmD, BCPS, NCMP

Nicole E. Cieri-Hutcherson, PharmD, BCPS, NCMP, has over a decade of experience as a pharmacist, professor, and researcher. She was a full-time clinical professor in the pharmacy practice department at D’Youville School of Pharmacy before subsequently joining the faculty of the pharmacy practice department at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences.

Edited by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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