Aromatase inhibitors: Uses, common brands, and safety info

Approximately 2 out of 3 breast cancers are classified as hormone receptor-positive breast cancer. This means that estrogen and/or progesterone are significantly responsible for cancer growth. 

Aromatase inhibitors are commonly used in postmenopausal women who have hormone receptor-positive breast cancer. Aromatase inhibitors are now the first choice for adjuvant endocrine therapy in this patient population. 

Three generations of aromatase inhibitors have been developed over the last 30 years. The third-generation aromatase inhibitors have replaced previous generations. They are better tolerated and more effective than the first and second-generation aromatase inhibitors. 

In this article, we will discuss the uses, common brand names, and safety information of aromatase inhibitors. The table below lists the three available aromatase inhibitors.

What are aromatase inhibitors?

Aromatase inhibitors (AIs) are prescription drugs approved by the U.S. Food and Drug Administration (FDA). They block a hormone called aromatase, which turns a hormone called androgen into estrogen. By blocking aromatase, aromatase inhibitors stop the production of estrogen. This means that there is less estrogen to stimulate breast cancer cell growth. 

Because they do not stop the ovaries from making estrogen, AIs are used in postmenopausal women. 

AIs are available in tablet form and are taken by mouth.

How do aromatase inhibitors work?

Estrogen can promote breast cancer cell growth. Aromatase inhibitors work by lowering estrogen levels. They stop an enzyme called aromatase from changing hormones into estrogen. This lowers estrogen levels. 

Aromatase inhibitors do not stop the ovaries from making estrogen. They only work in women who have already gone through menopause.

What are aromatase inhibitors used for?

Arimidex (anastrozole) is indicated for:

• Adjuvant treatment for hormone receptor-positive early-stage breast cancer in postmenopausal women.

• First-line treatment for hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer in postmenopausal women.

• Treatment of advanced breast cancer in postmenopausal women who have disease progression after taking tamoxifen.

Aromasin (exemestane) is indicated for:

• Adjuvant treatment for estrogen receptor-positive early breast cancer in postmenopausal women who have taken tamoxifen for 2 to 3 years, and take exemestane to complete a total of 5 consecutive years.

• Treatment of advanced breast cancer in postmenopausal women with disease progression after taking tamoxifen.

Femara (letrozole) is indicated for:

• Adjuvant treatment of hormone receptor-positive early breast cancer in postmenopausal women.

• Extended adjuvant treatment for postmenopausal women who have early breast cancer and have taken tamoxifen.

• First-line and second-line treatmentof hormone receptor-positive or hormone receptor unknown advanced breast cancer in postmenopausal women.

Studies have compared aromatase inhibitors with tamoxifen. Based on the results of these studies, doctors generally recommend that after initial treatment (of surgery and possibly chemotherapy and radiation):

• An aromatase inhibitor is the best hormonal therapy, with more benefits and fewer side effects than tamoxifen.

• Switching to an aromatase inhibitor after 2-3 years of tamoxifen (for a total of 5 years of hormone therapy) is better than 5 years of tamoxifen alone.

• Taking tamoxifen for 5 years, and then an aromatase inhibitor for 5 years after that, will help lower the chances of cancer coming back. 

Types of aromatase inhibitors 

There are two types of aromatase inhibitors: nonsteroidal and steroidal aromatase inhibitors. 

Nonsteroidal aromatase inhibitors

Nonsteroidal aromatase inhibitors bind to aromatase reversibly. These include Arimidex (anastrozole) and Femara (letrozole). 

Steroidal aromatase inhibitor 

Aromasin (exemestane) is a steroidal aromatase inhibitor. It irreversibly binds to aromatase.

Who can take aromatase inhibitors?

Below are general guidelines based on age and gender. However, only your healthcare provider can determine if an aromatase inhibitor is an appropriate treatment for you based on your medical conditions and history. 

Before taking an aromatase inhibitor, tell your doctor about all of your medical conditions and any medications you take, including prescription drugs, over-the-counter medicines, and vitamins or supplements.

Men

Aromatase inhibitors are only indicated in postmenopausal women. In some cases, doctors may occasionally prescribe an aromatase inhibitor off-label in a male patient, but there is not a lot of data on this population. 

Women

Postmenopausal women who fit the criteria and do not fall into one of the contraindications/restrictions can take an aromatase inhibitor. Women who are premenopausal, pregnant, or breastfeeding should not take an aromatase inhibitor. Women of childbearing age should use effective non-hormonal birth control while taking an aromatase inhibitor. Ask your healthcare provider what kind of non-hormonal birth control is best for you. 

Children 

There have been clinical trials of aromatase inhibitors in children with certain conditions. However, the studies failed to show efficacy. Currently, AIs are not approved for children.

Older adults and seniors

Postmenopausal women, older adults, and seniors can take an aromatase inhibitor if one of the indications apply and the doctor determines it is safe to do so. 

Are aromatase inhibitors safe?

Recalls

No aromatase inhibitor recalls found.

Restrictions

Do not take an AI if you are allergic to the drug(s) or any of its ingredients.

Premenopausal women should not take an aromatase inhibitor. 

Do not take an aromatase inhibitor if you are taking tamoxifen or medication that contains estrogen (such as estrogen-containing birth control or hormone replacement therapy).

Aromatase inhibitors can harm an unborn baby. Women who are pregnant should not take an aromatase inhibitor. Women of reproductive age should use effective contraception while taking an aromatase inhibitor and for at least 3 weeks after the last dose. 

Warnings 

Women with pre-existing ischemic heart disease should consult their health care professional before taking an aromatase inhibitor. In a breast cancer trial called the Arimidex, Tamoxifen, Alone, or in Combination (ATAC) study, there was an increased incidence of ischemic heart events. If you are taking an aromatase inhibitor and have chest pain or shortness of breath, get emergency medical help right away.

Discuss bone mineral density monitoring and risks with your doctor before taking an aromatase inhibitor. In the ATAC study, breast cancer patients who took Arimidex had a decrease in lumbar spine density and total hip bone mineral density.

Discuss cholesterol monitoring and risks with your doctor before taking an aromatase inhibitor. In the ATAC trial, more people who took Arimidex had increased cholesterol compared to people who took tamoxifen.

Aromatase inhibitors can cause lab abnormalities. Discuss this with your doctor before taking an aromatase inhibitor. 

Vitamin D levels and liver function should be checked before taking an aromatase inhibitor.

Some patients experience fatigue, dizziness, and sleepiness. Do not drive or operate machinery until you know how the medication affects you. 

Can you take aromatase inhibitors while pregnant or breastfeeding?

Pregnancy

There are no studies of aromatase inhibitors in pregnant women. However, they have been shown to cause fetal harm in animal studies. Before taking an aromatase inhibitor, pregnancy status should be verified. While taking an aromatase inhibitor (and for at least 3 weeks after the last dose), effective contraception should be used. 

Also, based on animal studies, aromatase inhibitors may impair fertility in women and men. 

Breastfeeding

There are no studies of aromatase inhibitors and human milk. However, based on the results of animal studies, the manufacturers advise that women should not breastfeed while taking an aromatase inhibitor and for some time after the last dose. 

Are aromatase inhibitors controlled substances?

No, aromatase inhibitors are not controlled substances.

Common aromatase inhibitors side effects

The most common side effects of aromatase inhibitors include:

• Hot flashes

• Tiredness 

• Weakness 

• Pain

• Joint pain and/or stiffness

• Bone pain

• Muscle pain

• Breast pain 

• Chest pain 

• Carpal tunnel syndrome 

• Blood clots

• Arthritis 

• Nausea

• Vomiting 

• Diarrhea

• Constipation 

• Abdominal pain 

• Sweating/night sweats

• Flushing 

• Headache 

• Hair loss 

• Sore throat

• Depression 

• Rash 

• High blood pressure (hypertension)

• Swelling of the arms or legs

• Insomnia 

• Weight gain 

• Appetite loss

• Shortness of breath

• Visual disturbances

• High cholesterol

• Osteoporosis 

• Fractures 

• Cough 

• Tingling 

• Infection 

• Cataracts 

Serious effects can occur (some of them are also listed above as common). These may include:

• Fractures 

• Osteoporosis 

• Endometrial cancer 

• Blood clots 

• Heart attack (myocardial infarction)

• Heart failure

• Stroke 

• Chest pain 

• High blood pressure 

• Cataracts 

• Low red blood cells (anemia) 

• Low white blood cells

• Skin disorder with bullseye-shaped lesions (erythema multiforme)

• Stevens-Johnson syndrome

• Jaundice 

• Allergic/hypersensitivity reaction

• Severe allergic reaction

• Severe skin reaction 

While allergic reactions are rare, if you experience symptoms such as shortness of breath, hives, or swelling of the lips, tongue, or face, get emergency medical help right away.

This is not a full list of side effects. Talk to your doctor before using an aromatase inhibitor about what side effects to expect and how to address them.

How much do aromatase inhibitors cost?

The price for an aromatase inhibitor prescription varies by insurance coverage. Most insurance and Medicare prescription plans cover generic aromatase inhibitors, but the copay or coinsurance will vary by plan. You can contact your insurance company for up-to-date coverage information, as plans may change. You can always use a free SingleCare card or coupon on your prescription and refills to save up to 80% at any participating pharmacy.