Hormone Therapy for Endometrial Cancer

This type of treatment uses hormones or hormone-blocking drugs to treat cancer. It’s not the same as the hormone therapy given to ease the symptoms of menopause (menopausal hormone therapy). Hormone therapy can be      used to treat advanced endometrial cancer (stage III or IV) or cancer that has come back after treatment (recurred).  It is also used for early-stage cancer when surgery is not an option, or in patients who wish to keep the uterus to save their fertility. It’s usually also considered for cancer that is lower-grade, low volume, and slow growing.      

Hormone treatment for endometrial cancer

Hormone treatment for endometrial cancer can include:

• Progestins (this is the main hormone treatment used)
• Aromatase inhibitors (AIs)
• Tamoxifen
• Fulvestrant
• CDK 4/6 inhibitors

At this time, no one type of hormone treatment has been found to be the best for endometrial cancer.

Progestins

The main hormone treatment for endometrial cancer uses progesterone or drugs like it (called progestins).

The progestins used to manage endometrial cancer are:

• Medroxyprogesterone acetate (Provera^®), which can be given as an injection or as a pill
• Megestrol acetate (Megace^®), which can be given as a pill or liquid
• Levonorgestrel intrauterine device (IUD) which is placed inside the uterus and releases levonorgestrel daily for many years. This is the preferred hormonal treatment for patients with endometrial cancer that has not spread beyond the uterus and who are unable to have surgery or who choose not to have surgery because of plans for a future pregnancy.

Side effects of progestins can include:

• Hot flashes
• Night sweats
• Weight gain (from fluid retention and an increased appetite)
• Worsening of depression
• Increased blood sugar levels in women with diabetes
• Serious blood clots (this is rare)

Aromatase inhibitors (AIs)

Before menopause, most estrogen is made by the ovaries.  Even after the ovaries are removed (or are not working), estrogen is still made in fat tissue by an enzyme called aromatase. Aromatase inhibitors work by preventing aromatase from making estrogen. 

Examples of aromatase inhibitors are:

• Letrozole (Femara^®)
• Anastrozole (Arimidex^®)
• Exemestane (Aromasin^®)

These drugs are most often used to treat breast cancer, but can be helpful in treating endometrial cancer, too. These drugs are taken as pills, typically once a day.

Common side effects of aromatase inhibitors can include:

• Joint and muscle pain
• Mood changes
• Vaginal dryness
• Hot flashes

If taken for a long time (years), these drugs also can weaken bones, sometimes leading to osteoporosis. These drugs are still being studied for how to best use them to treat endometrial cancer.

Tamoxifen

Tamoxifen is an anti-estrogen drug that can be used to treat advanced or recurrent endometrial cancer. Alternating a progestin and tamoxifen seems to work well and be better tolerated than giving a progestin alone.

Tamoxifen blocks estrogen from connecting to the cancer cells and telling them to grow and divide. It is a pill taken by mouth, daily.

Common side effects of tamoxifen include:

• Hot flashes
• Vaginal dryness

Rare but serious side effects include blood clots in the legs (called deep vein thrombosis or DVT) or blood clots in the lungs (called pulmonary emboli or PE).

Fulvestrant

Fulvestrant is an anti-estrogen drug also called a selective estrogen receptor degrader (SERD),  that can be used to treat advanced or recurrent endometrial cancer. It is given as 2 injections into the buttocks. For the first month, the 2 shots are given 2 weeks apart. After that, they are given once a month.

Common side effects of fulvestrant include:

• Hot flashes and/or night sweats
• Headache
• Nausea
• Feeling tired
• Loss of appetite
• Muscle, joint, or bone pain

CDK 4/6 inhibitors  

Some endometrial cancers are hormone (estrogen or progesterone) receptor-positive. For these uterine cancers, CDK 4/6 inhibitors may be a treatment option. 

Ribociclib (Kisqali) and abemaciclib (Verzenio) are drugs that block proteins in the cell called cyclin-dependent kinases (CDKs), particularly CDK4 and CDK6. Blocking these proteins in hormone receptor-positive uterine cancer cells helps stop the cells from dividing. This can slow cancer growth. Ribociclib or abemaciclib can be given with an AI (letrozole). These drugs are pills typically taken once or twice a day.

The most common side effects of CDK4/6 inhibitors include:

• Low blood cell counts (low white cell counts can increase the risk of infection)
• Fatigue

Less common side effects include:

• Nausea and vomiting
• Mouth sores
• Hair loss
• Diarrhea
• Headache

A rare but possible life-threatening side effect is inflammation of the lungs, also called interstitial lung disease or pneumonitis.