9 Side Effects of Aromatase Inhibitors (Like Anastrozole) and How to Manage Them

If you’ve been diagnosed with breast cancer, you’re not alone. It affects the lives of millions of women every year, so researchers have made it a priority to find treatments that work. Today, you and your cancer specialist have many breast cancer medications to choose from.

Chemotherapy is one option — but it's far from the only one. In many cases, your treatment plan will include medications that work on specific cancer targets in your body. One of these targets includes a protein called the estrogen receptor. This is a type of hormone receptor.

Aromatase inhibitors (AIs) are a common group of breast cancer medications that treat hormone receptor-positive breast cancer. If you have this type of cancer, it’s likely that you’ll encounter an AI at some point in your treatment journey.

AIs come with a unique set of side effects. Knowing what to expect and how to manage them can help make your treatment experience run a bit smoother.

What is an aromatase inhibitor?

AIs are oral medications that lower estrogen levels in your body. FDA-approved aromatase inhibitors include anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara). They’re hormone therapy medications, not chemotherapies.

How do aromatase inhibitors work?

Hormone-receptor positive cancers use estrogen and/or progesterone to help them grow. AIs lower estrogen levels to treat this version of breast cancer.

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In terms of risks, AIs tend to cause fewer side effects than chemotherapy. But because these medications lower your estrogen levels, some of their common side effects are similar to what people experience when going through menopause.

1. Hot flashes

Hot flashes are an unfortunate consequence of lowering estrogen in your body. They cause a sudden, intense feeling of heat that can lead to sweating and anxiety. If you’ve experienced menopause, you’re likely all too familiar with this side effect.

Hot flashes are a common AI side effect. They can occur in up to 36% of people who take them. Thankfully, there are many medication-free treatments that you can try. You should:

• Avoid smoking, caffeine, and alcohol, as they can all worsen hot flashes. 

• Keep your body cool by wearing light clothing, sleeping with a fan on, and taking cool showers.

• Try relaxation techniques, such as meditation or yoga.

If these strategies aren’t cutting it, talk to your healthcare provider about prescription medication. Typical options include antidepressants or gabapentin. But avoid taking supplements for hot flashes unless it’s been OK’d by your healthcare team. Some supplements can cause harm or interact with your other medications.

2. Vaginal changes

Vaginal dryness is another common side effect of low estrogen. It can cause irritation and make sex more painful. However, AIs can cause you to experience pain during sex even without dryness.

It might feel uncomfortable to talk about, but sexual health can have a big impact on your day to day life. Luckily, there are strategies to help you through it. Over-the-counter (OTC) options like vaginal moisturizers and lubricants are a good first step in treating dryness. Moisturizers should be used regularly, while lubricants only need to be used during sex. 

If OTC options don’t work, the next step may potentially include trying vaginal estrogen tablets or inserts (Vagifem, Imvexxy), creams (Estrace), or rings (Estring). However, it’s important to ask your healthcare provider if this type of treatment is appropriate for you. Many women with hormone-receptor positive breast cancer avoid topical estrogen.

3. Joint, muscle, or bone pain

It’s common for AIs to cause painful symptoms that affect your muscles, bones, and joints. Muscle and joint pain (and stiffness) can start any time during AI treatment. But it’s more common to start noticing it about 6 weeks after starting your medication. 

As many as three-fourths of people taking AIs will experience these symptoms at some point during treatment. So what can you do? Various types of exercise, like yoga and strength training, have proven benefits. Maintaining a healthy body weight can also lower your risk.

You can also consider acupuncture or a prescription medication, such as duloxetine (Cymbalta). Other options could include stopping your AI for a short period, switching to an alternative AI, or trying an estrogen blocker, like tamoxifen (Soltamox). But don’t stop your AI without speaking with your provider first — doing this on your own could lower the effectiveness of your medication.

4. Trouble sleeping

Trouble sleeping is another common AI side effect. And this is not just because decreased estrogen can affect sleep quality. Hot flashes and joint or muscle pains could all play a role in keeping you up at night. 

There are many strategies out there to improve your sleep hygiene. These include:

• Avoiding screens an hour before bedtime

• Keeping your bedroom cool and dark

• Having a consistent bedtime and wake time

If you’re having trouble sleeping because of hot flashes or pain, treating the underlying issue could do the trick. And if you need a little extra help, your provider may have you try a short-term prescription medication, such as zolpidem (Ambien) or trazodone.

5. Nausea

Nausea is another possible AI side effect. You can take anastrozole and letrozole with or without a meal, but taking it with food might help decrease nausea. Exemestane should be taken with food, even if you aren’t having nausea. 

If food doesn’t help, there are a few other things you can try at home. These include:

• Eating smaller, more frequent meals throughout the day

• Avoiding spicy, high-fiber, or fried foods

• Trying an OTC antacid, such as calcium carbonate (Tums) or bismuth subsalicylate (Pepto-Bismol)

If those aren’t providing relief, you can reach out to your provider for a prescription nausea medication.

6. Fatigue

Most cancer treatments cause some form of tiredness. Hormonal treatments are no exception. Over half of people taking AIs report fatigue. Just like sleep, fatigue is dependent on many factors. And it could also be a direct result of trouble sleeping at night. 

Your provider can work with you to determine the cause(s) of your fatigue. It’s possible it may be due to other treatable conditions — such as anemia or insomnia. Regardless of the cause, carving out time for rest and naps throughout the day might help. In addition, exercise, yoga, and talk therapy all have proven benefits.

7. Bone loss

Estrogen plays a role in keeping our bones healthy. So when AIs lower your estrogen levels, it can have an impact on your bone health. Taking AIs for longer periods of time (2 years or more) can raise the risk of bone loss or osteoporosis — a condition that raises your risk of broken bones.

To help minimize this side effect, your healthcare provider may have you take a bone-strengthening medication — such as denosumab (Prolia) or zoledronic acid (Reclast) — along with calcium and vitamin D supplements.

8. Heart problems

AIs may potentially raise the risk of heart problems, such as heart failure, heart attacks, and other forms of cardiovascular disease. So it’s important to tell your healthcare provider if you are experiencing the following symptoms:

• Chest pain

• Shortness of breath

• Increased fatigue, even with light exertion

• Swelling in your legs

• Episodes of excessive sweating (especially if they don’t seem to be related to a hot flash)

If you have a history of heart problems — including complications from chemotherapies like doxorubicin — make sure your healthcare provider is aware of them before starting an AI. This could make a difference in which breast cancer treatment they recommend. And they can also monitor your heart health throughout your treatment.

9. Liver damage

AI medications can sometimes raise liver enzymes (proteins). While rare, this is a possible sign of liver damage. These medications have also been linked to a condition called autoimmune hepatitis, which causes inflammation in the liver.

Signs or symptoms of liver problems aren’t always easy to discern, but they can include:

• Yellow-colored skin or eyes (jaundice)

• Severe or ongoing abdominal pain 

• Significant bloating and fluid in the abdomen

• Nausea or vomiting that doesn’t go away

Your healthcare provider may do occasional testing to monitor for these more serious side effects. However, you should always let your healthcare provider know if you experience anything unusual.

How long do you have to take aromatase inhibitors?

AIs are given for different amounts of time. This depends on the way your healthcare provider is treating your cancer. A typical time frame ranges from 5 to 10 years.

Sometimes, people will switch estrogen-lowering medications after taking one for a few years. This could mean you take an AI for less than 5 years. However, your total time taking hormonal medication will most likely be at least 5 years. For example, you may take tamoxifen for 2 to 3 years, followed by an AI for the remainder of the treatment time.

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Written by:

Rachel Feaster, PharmD, BCOP, BCPS

Rachel Feaster has over 10 years of professional experience in ambulatory, inpatient, pharmacogenomics, and oncology care. She is board certified in oncology and pharmacotherapy.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Katie E. Golden, MD

Katie E. Golden, MD, is a board-certified emergency medicine physician and a medical editor at GoodRx.

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