What Are SERMs?

Selective estrogen receptor modulators change how estrogen affects the body

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Selective estrogen receptor modulators (SERMs) are a group of medications classified as hormone therapies. Two common SERMs are Nolvadex (tamoxifen) for the treatment of breast cancer and Evista (raloxifene) for osteoporosis (progressive bone thinning).

These medications act on a protein in some cells of the body called the estrogen receptor. The estrogen receptor binds to the hormone estrogen, sending a signal to the cell. This signal causes the cells to grow and can exert other effects.

This article will explain selective estrogen receptor modulators, how they work, what they are, and the most common kinds. It will also discuss side effects and safety and how healthcare providers prescribe them for osteoporosis, breast cancer, and other conditions.

Person with breast cancer consults telehealth provider about SERMs

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The ovaries (egg-producing organs) release the hormone estrogen during the menstrual cycle, as do the adrenal glands, fat, and skin. During pregnancy, the placenta releases estrogen. Estrogen can impact tissues differently based on how their cells are programmed to react to it.

Estrogen affects the growth of mammary tissue, hair growth, and the menstrual cycle. When estrogen is too high or too low, menstrual periods may be irregular, and mood, bone health, and heart health can be affected.

Estrogen is also an important factor fueling the growth of some breast cancers and is important in growing long bones, like the limb bones.

Estrogen Modulators

Compounds that act as “modulators” can attach to the estrogen receptor to change its activity. For example, SERMs are modulators for some estrogen receptors—turning up or down the effects of estrogen through binding to its receptor.

In some tissues, including breast tissue, SERMs block the effects of estrogen. In others, they act like estrogen, binding the receptor. Different SERMs are active in various tissues.

When estrogen changes in the body lead to an illness, SERMs may be a treatment option. These illnesses include estrogen receptor-positive (ER+) breast cancers, osteoporosis, and menopause (the cessation of menstruation). 

Types of SERM Drugs

The differences between SERMS come down to what tissues they act upon and if they also mimic estrogen in some tissues. These differences play a role in who gets prescribed these medications and for which conditions. 

Tamoxifen (Nolvadex, Soltamox)

Tamoxifen is a SERM used as hormone therapy to treat breast cancer. It’s primarily used in people of any sex whose cancer has spread to other body parts and in females with early breast cancer after other therapies.

For people with stage 0 breast cancer (ductal carcinoma in situ) Tamoxifen can help reduce the risk of developing a more serious type of breast cancer.

Alternate names for tamoxifen include the brand names Nolvadex and Soltamox. Tamoxifen is taken as a daily pill by mouth. It is also available as a liquid. 

Raloxifene (Evista, Keoxifene)

Raloxifene is a SERM used to prevent and treat osteoporosis (a thinning of the bones that can lead to fractures) by mimicking the effects of estrogen in the bones, which makes them denser and thicker.

It can also decrease the risk of developing invasive breast cancer for postmenopausal people at high risk. Raloxifene should not be prescribed to people who menstruate who have not reached menopause. It is also known by the brand names Evista and Keoxifene

Raloxifene is taken as a tablet daily by mouth. Healthcare providers recommend getting a lot of foods rich in calcium and vitamin D while taking raloxifene.

Other Less Common SERMs

Less common SERMs include:

  • Fareston (toremifene) is another SERM that works similarly to tamoxifen. It is less common and only approved to treat postmenopausal people with metastatic breast cancer (breast cancer that has spread to other areas of the body). You take it as a tablet by mouth once a day.
  • Fablyn (lasofoxifene) is a SERM that is not approved in the U.S. It is being tested as a treatment option for metastatic breast cancer and osteoporosis.
  • Bazedoxifene is similar to raloxifene and is used to treat osteoporosis. It blocks the action of estrogen on the lining of the uterus (womb), decreasing the risk of overgrowth that may lead to cancer. It’s available as a combination drug with conjugated estrogen under the brand name Duavee for treating moderate to severe symptoms of menopause and preventing postmenopausal osteoporosis.

Benefits of SERMs

When used in the right treatment groups, SERMs can improve bone density in people with osteoporosis, reduce the likelihood of some fractures due to low bone density, and reduce the risk that breast cancer will develop or come back after treatment. 

SERMs for Osteoporosis

SERMS like Evista (raloxifene) can help improve bone density in people with osteoporosis. It can prevent low bone density from becoming osteoporosis and reduces the risk of vertebral fractures.  They act by turning down the bone cells in charge of breaking down bone and reabsorbing its nutrients.

SERMs for Breast Cancer

Tamoxifen, as hormone therapy, can treat ER+ breast cancer. In the cancer cells, tamoxifen stops estrogen from binding to the receptor, stopping the signal telling cancer to grow.

People being treated for breast cancer typically take the drug after surgery and other treatments, typically for five years and sometimes longer. Healthcare providers will sometimes prescribe toremifene in place of tamoxifen.

All SERMs, including raloxifene, can help prevent breast cancer in high-risk people. Either tamoxifen or raloxifene may reduce the risk of developing breast cancer by 40%.

SERMs for Other Conditions

Some SERMs—specifically bazedoxifene—are combined with a mixture of estrogens (called conjugated estrogens) to treat moderate-to-severe hot flashes and other vasomotor symptoms of menopause (temperature dysfunction).

The SERM selectively blocks the estrogens from impacting the uterus, reducing the likelihood that the estrogens will lead to cancer.

SERMs vs. Aromatase Inhibitors

SERMS are similar to another class of drugs called aromatase inhibitors. Aromatase inhibitors are another type of hormone therapy. They are used more often for people who have gone through menopause. 

Aromatase inhibitors act to stop estrogen from being made, decreasing the amounts of and effects of this hormone in the body.

Common aromatase inhibitors used to treat breast cancer include:

Side Effects of SERMs

Because they act on estrogen receptors, SERMs mimic menopause in people who menstruate. Side effects of SERMs may include symptoms of menopause. These can include:

  • Hot flashes
  • Leg cramps 
  • Night sweats 

Other more dangerous side effects can happen but are rare. These include blood clots—known as deep vein thrombosis in the leg and pulmonary embolism in the lungs—leading to serious problems and even death.

Raloxifene Side Effects

Raloxifene may cause side effects. These can include:

  • Painful urination, including a burning sensation 
  • Bloody or cloudy urine
  • Flu-like or cold-like symptoms including fever and joint or muscle pain
  • Chest pain, cough, wheezing, rapid breathing, or fast heart rate
  • Swelling of the hands, feet, ankles, or lower legs
  • Vaginal itching or white discharge
  • Insomnia (difficulty falling asleep or staying asleep)
  • Digestive issues, including vomiting, upset stomach, and gas
  • Unexplained weight gain

Mention these symptoms to your healthcare provider if they are severe or do not go away.

Tamoxifen Side Effects

While tamoxifen has been a game-changing drug for breast cancer care, there are some possible side effects you should be aware of.

Tumor flare: If you’re taking tamoxifen as a treatment for cancer that has spread to the bones, you may experience a tumor flare, in which the tumor gets bigger for a short time and causes bone pain. The tumor flare can lead to a high calcium level in the blood that is hard to control.

Uterine cancer: Some SERMs increase the risk of developing uterine cancer and endometrial pre-cancers. Tell your healthcare provider if you have vaginal bleeding, pelvic pain or pressure, irregular periods, or unusual vaginal discharge, especially if you’re post-menopausal. 

Signs of Uterine Cancer

If you are taking tamoxifen, tell your healthcare provider if you have any abnormal vaginal bleeding or spotting, especially after menopause, as these are possible symptoms of uterine cancer.

Other common side effects of tamoxifen can include:

  • Vaginal dryness, itching, or discharge 
  • Menstrual changes, leading to periods becoming irregular or even stopping, sometimes leading to menopause
  • Loss of sexual desire
  • Stroke
  • Bone thinning (pre-menopausal people only)
  • Increased risk of cataracts (clouding of the lens in the eye) that may need surgery to repair

Mention these symptoms to your healthcare provider if severe or do not go away.

Side Effects of Toremifene 

Toremifene may cause QT prolongation (an irregular heart rhythm that can lead to fainting, loss of consciousness, seizures, or sudden death).

Other side effects of toremifene include:

  • Vision changes, including blurring, sensitivity to light, halos around lights, difficulty seeing at night, or fading or yellowing of colors
  • Dry eyes
  • Swelling of the hands, feet, ankles, or lower legs
  • Redness of the face, neck, arms, and occasionally the upper chest
  • Sudden or excessive sweating

Mention these symptoms to your healthcare provider if they are severe or do not go away.

Are SERMs Safe?

SERMs are generally safe for use according to prescribing guidelines. The risk of developing more dangerous side effects like uterine cancer or blood clots is relatively low:

  • The risk of developing blood clots is under 1% over five years of treatment with SERMs, but may be higher in those who have previously had a clot or are at increased risk for clots.
  • The risk of uterine cancer with tamoxifen use is less than 1%.


Selective estrogen receptor modulators (SERMs) are a class of drugs that impact the action of estrogen and the estrogen receptors in the body. They can prevent breast cancer and treat it and osteoporosis. They’re generally safe but may have some serious or mild side effects.

Frequently Asked Questions

  • How do SERMs differ from estrogen?

    SERM stands for selective estrogen receptor modulators, which means these drugs act on the estrogen receptor. They don’t change the estrogen level in the body but can impact how the body responds to the hormone.

  • Are SERMs safe for dense breasts?

    People with dense breast tissue have more connective tissue than fatty tissue. Dense breast tissue puts them at a higher risk of developing breast cancer. Therapy with tamoxifen can reduce breast density, potentially lowering the risk of breast cancer.

13 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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Additional Reading

By Jennifer Welsh
Jennifer Welsh is a Connecticut-based science writer and editor with over ten years of experience under her belt. She’s previously worked and written for WIRED Science, The Scientist, Discover Magazine, LiveScience, and Business Insider.