Myfembree vs. Orilissa: 5 Things to Know When Comparing These Endometriosis Treatments

Endometriosis is a condition in which the tissue of the uterine lining (endometrium) grows in areas outside of the uterus. Endometriosis can be very painful, cause heavy menstruation, and make it hard to get pregnant.

Myfembree (estradiol / norethindrone / relugolix) and Orilissa (elagolix) are two endometriosis treatments. They have some similarities, but they also have a number of differences to know about. Below, we’ll discuss five things to keep in mind when considering Myfembree versus Orilissa for endometriosis.

1. Myfembree and Orilissa have different active ingredients

Orilissa contains one active ingredient: elagolix, a gonadotropin-releasing hormone (GnRH) antagonist. Elagolix reduces the release of estrogen in the body. Estrogen stimulates the growth of uterine tissue, which can worsen endometriosis symptoms. When Orilissa lowers the release of estrogen, uterine tissue doesn’t grow as much. And this helps improve pain caused by endometriosis.

Myfembree contains a GnRH antagonist called relugolix. But it also contains small amounts of two lab-made hormones: estradiol (an estrogen) and norethindrone (a progestin). This addition of estradiol and norethindrone is known as “add-back therapy.”

Adding hormones to relugolix may seem counterintuitive. But it can help lower the risk of long-term side effects from the GnRH antagonist. When taken without add-back therapy, GnRH antagonists have a higher risk of causing bone mineral density (BMD) loss and fractures (broken bones).

2. Myfembree and Orilissa have different FDA-approved uses

Myfembree is FDA approved to improve moderate-to-severe endometriosis pain. It’s also approved to reduce heavy menstruation caused by uterine fibroids. Fibroids are noncancerous growths that occur in and around the uterus.

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Like Myfembree, Orilissa is approved for moderate-to-severe endometriosis pain. But it doesn’t have other FDA-approved uses.

3. Myfembree and Orilissa have different recommended dosages

Myfembree and Orilissa are both oral tablets. But there are differences when it comes to their recommended dosages.

Myfembree comes as a tablet that contains 40 mg of relugolix, 1 mg of estradiol, and 0.5 mg of norethindrone. The typical dosage is 1 tablet by mouth once daily with or without food. It doesn’t matter what time of day you take Myfembree. But be sure to take it around the same time each day.

Orilissa comes as 150 mg and 200 mg tablets. Most people take 150 mg by mouth once daily. But in some cases, healthcare professionals may prescribe a dosage of 200 mg by mouth twice daily. Orilissa should be taken around the same time each day and can be taken with or without food.

Good to know: Because both Myfembree and Orilissa can cause low BMD and fractures, most people should only take them for up to 24 months (2 years). Though, if you're taking the higher, twice-daily Orilissa dosage, you should only take the medication for up to 6 months.

4. Myfembree and Orilissa share some common side effects

Myfembree and Orilissa share some common side effects. But they also have some unique side effects.

Notable side effects for Myfembree and Orilissa can be found in the table below. But keep in mind that these aren’t comprehensive lists.

Bone loss with Myfembree and Orilissa

Both Myfembree and Orilissa carry a risk of decreased BMD, which can raise your risk of fractures. This serious side effect happens because Myfembree and Orilissa lower estrogen levels in the body. And estrogen helps protect the bones.

The risk of low BMD is why it’s only recommended to take Myfembree and Orilissa for up to 2 years. Taking the medications for as short of a time as possible helps to minimize this risk.

This serious side effect is also why Myfembree contains estradiol. Research shows that add-back therapy helps significantly lower the risk of reduced BMD. So if you’re taking Orilissa, your prescriber may suggest that you also take estrogen-containing pills as add-back therapy. This provides similar benefits to taking a combination pill like Myfembree.

5. Myfembree and Orilissa have different interactions

Myfembree and Orilissa have different drug interactions, because the body breaks down (metabolizes) these medications in different ways. Depending on what other medications you’re taking, your prescriber may recommend one of the endometriosis treatments over the other.

Some medications can affect how your body metabolizes and clears Myfembree or Orilissa. This could either raise your risk of side effects or cause your endometriosis treatment to be less effective. It’s also possible for Myfembree and Orilissa to affect how other medications work. In some cases, dosage adjustments of one or more medications can help manage interactions. Other times, you may need to avoid the combinations altogether.

Some of the medications that Myfembree and Orilissa interact with can be found in the table below. But be sure to share a full list of the medications you take with your prescriber and pharmacist. They can use this list to help you avoid serious interactions.

How to save on Myfembree and Orilissa

There are ways to save on Myfembree and Orilissa, which are available as brand-name medications. GoodRx can help you navigate between patient assistance programs and copay savings cards to save money on your prescription:

• Save with a copay savings card. If you have commercial insurance, you may be eligible to pay as little as $5 per prescription for Myfembree or $5 per month for Orilissa using a savings card from the manufacturer.

• Save with a patient assistance program. If you’re uninsured or underinsured, you may be eligible for Myfembree or Orilissa’s patient assistance program. These programs offer the medications free of cost to eligible consumers.

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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:

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.

Reviewed by:

Tegan Smedley, PharmD, APh

Tegan Smedley, PharmD, APh, has 10 years of experience as a pharmacist. She has worked in a variety of settings, including retail, hospital, and ambulatory care.

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