Activella (Estradiol and Norethindrone) – Oral

What Is Activella?

Activella (estradiol and norethindrone) is an orally prescribed medication option used to relieve moderate to severe menopausal symptoms in people assigned female at birth. Activella can also be used to prevent postmenopausal osteoporosis.

Activella is defined as a combination hormone therapy.

Specifically, it contains a form of estrogen and a human-made version of progesterone, which are defined as sex hormones.

This medication works by influencing sex hormones. Hormone replacement therapy works by replacing estrogen hormones that are no longer being made by the body.

While also available as a generic product, similar brand-name drugs that contain the estradiol and norethindrone combination ingredients include Amabelz and Mimvey.

This article will focus on the oral (taken by mouth) use of Activella.

Drug Facts

Generic Name: Estradiol and norethindrone

Brand Name(s): Activella, Amablez, Mimvey

Drug Availability: Prescription

Therapeutic Classification: Estrogen/progestin combination

Available Generically: Yes

Controlled Substance: N/A

Administration Route: Oral

Active Ingredient: Estradiol/norethindrone acetate

Dosage Form(s): Tablet

What Is Activella Used For?

Activella has been approved by the Food and Drug Administration (FDA) to treat low levels of estrogen, commonly resulting in vaginal dryness and night sweats, a byproduct of menopause. The FDA also approved Activella to prevent osteoporosis—a medical condition of weak bones—after menopause.

In people assigned female at birth, menopause is a normal part of life—with 52 being the average age of onset of menopause in the United States (U.S.). Once menopause is reached, your menstrual periods permanently stop.

Hormonal changes can cause symptoms that can go away without any treatment.

Some people assigned female at birth, however, might experience discomfort from their symptoms, which may include hot flashes and night sweats. Activella is a medication option that may help relieve these symptoms.

Menopause also can cause symptoms of low sex drive and other sexual-related symptoms, including painful sex due to vaginal dryness and itchiness.

If Activella is needed only just for these vaginal symptoms, the FDA recommends trying topical vaginal products first.

Since Activella is a combined hormone therapy, it is used for people who still have their uterus, meaning they have not had a hysterectomy (surgical removal of the uterus).

How to Take Activella

Activella comes as a tablet containing estrogen and progestin.

Take one tablet every day. To help you remember to take hormone replacement therapy, take it around the same time daily. Follow the directions on your prescription label carefully, and ask your healthcare provider to explain anything you do not understand.


Because Activella is a noncontrolled prescription, meaning it's not regulated by law regarding possession and use, your healthcare provider can approve refills for up to one year from the originally written date on the prescription.

Your healthcare provider may want to see you every three to six months to weigh the benefits and risks of continuing hormone therapy and, at that time can authorize fewer refills.

When you bring Activella home from the pharmacy, store the medication in a dry place and at room temperature, which is around 68 to 77 degrees F.

Activella has a safe storage temperature range between 59 to 86 degrees F for short excursions.

If you’re going to travel with Activella, know your final destination’s regulations. In general, however, make a copy of your Activella prescription and carry it with you.

Also, keep the medication in its original container or packaging—with your name on it—from the pharmacy.

How Long Does Activella Take to Work?

Within four weeks of taking Activella, you might notice an improvement in your menopausal symptoms.

What Are the Side Effects of Activella?

This is not a complete list of side effects, and others may occur. A healthcare provider can advise you on side effects.

If you experience other symptoms, contact your pharmacist or a healthcare provider. You may report side effects to the FDA at or 800-FDA-1088.

Common Side Effects

Some of Activella’s common side effects include:

Severe Side Effects

Get medical help right away if you experience the following serious side effects:

Long-Term Side Effects

Long-term use of Activella raises the likelihood of:

Report Side Effects

Activella may cause other side effects. Call your healthcare provider if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your provider may send a report to the FDA's MedWatch Adverse Event Reporting Program or by phone (800-332-1088).

Dosage: How Much Activella Should I Take?

Drug Content Provided and Reviewed by IBM Micromedex®

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (tablets):
    • For moderate to severe hot flashes:
      • Adults—One tablet once a day. Each tablet contains 1 milligram (mg) of estradiol and 0.5 mg of norethindrone or 0.5 mg of estradiol and 0.1 mg of norethindrone.
      • Children—Use is not recommended.
    • For moderate to severe vaginal problems or dryness:
      • Adults—One tablet once a day. Each tablet contains 1 milligram (mg) of estradiol and 0.5 mg of norethindrone.
      • Children—Use is not recommended.
    • For prevention of osteoporosis after menopause:
      • Adults—One tablet once a day. Each tablet contains 1 milligram (mg) of estradiol and 0.5 mg of norethindrone, or 0.5 mg of estradiol and 0.1 mg of norethindrone.
      • Children—Use is not recommended.


Users should be aware of the following before beginning Activella:

Pregnant or nursing people: Since Activella is used during or after menopause, it’s not meant to be taken by individuals who are pregnant or breastfeeding.

There is no effectiveness and safety data for Activella in pregnant people. However, combination birth control has not led to negative effects on the unborn baby during early pregnancy.

As for nursing parents, estrogen and progesterone are present in breast milk. As a result, the manufacturer—Amneal Pharmaceuticals—recommends weighing the benefits and risks of Activella therapy while nursing.

Postmenopausal people assigned female at birth: Due to a higher risk of breast cancer, stroke, blood clots, and dementia with Activella in postmenopausal people assigned female at birth—who are 50 or older, the manufacturer recommends taking this medication at the lowest effective dose for the shortest amount of time necessary—depending on goals and risks of treatment.

Adults 65 and older: There have not been sufficient numbers of people of this age involved in clinical studies to determine whether those over 65 differ from younger people in their response to Activella. 

As such, speak with your healthcare provider if you think your age will impact your ability to tolerate it.

Missed Dose

If you accidentally forget to take an Activella dose, take it as soon as you remember. If it’s close to your next scheduled dose, however, then skip the missed dose and take the following dose at the next scheduled dosing time.

Don’t try to double up and take more than one dose to make up for the missed one.

Overdose: What Happens If I Take Too Much Activella?

If you accidentally take too many Activella tablets, you may experience the following symptoms:

If you took too much Activella, get medical help right away or contact the Poison Control Center.

What Happens If I Overdose on Activella?

If you think you or someone else may have overdosed on Activella, call a healthcare provider or the Poison Control Center (800-222-1222).

If someone collapses or isn't breathing after taking Activella, call 911 immediately.


Drug Content Provided and Reviewed by IBM Micromedex®

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly and does not cause unwanted effects. These visits may be every 3 to 6 months. Blood or urine tests, pelvic exam, breast exam, and mammogram (breast x-ray) may be needed to check for unwanted effects, unless your doctor tells you otherwise. Be sure to keep all appointments.

It is unlikely that a postmenopausal woman may become pregnant. But, you should know that using this medicine while you are pregnant could harm your unborn baby. If you think you have become pregnant while using the medicine, tell your doctor right away.

Using this medicine may increase your risk for having blood clots, strokes, or heart attacks. This risk may continue even after you stop using the medicine. Your risk for these serious problems is even greater if you have high blood pressure, high cholesterol in your blood, diabetes, or if you are overweight or smoke cigarettes. Contact your doctor immediately if you experience chest pain, confusion, difficulty speaking, double vision, headaches, an inability to move arms, legs or facial muscle, or an inability to speak.

Using this medicine for a long period of time may increase your risk of endometrial cancer, breast cancer, or uterine cancer. Talk with your doctor about this risk. Do not use this medicine if you have had your uterus (womb) removed (hysterectomy). Check with your doctor immediately if your experience abnormal vaginal bleeding.

Using this medicine may increase your risk of dementia, especially in women 65 years of age and older.

This medicine may increase your risk of having gallbladder disease. Check with your doctor if you start to have stomach pains, nausea, and vomiting.

Check with your doctor immediately if severe headache or sudden loss of vision or any other change in vision occurs while you are using this medicine. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).

Tell your doctor or dentist who treats you knows that you are using this medicine before any kind of surgery (eg, surgery that will require inactivity for a long time) or emergency treatment. Your doctor will decide whether you should continue using this medicine. This medicine may also affect the results of certain medical tests.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

What Are Reasons I Shouldn't Take Activella?

If any of the following applies to you, Activella isn’t an ideal therapy for you:

  • Abnormal vaginal bleeding without a healthcare provider’s awareness or follow-up care
  • Estrogen-dependent neoplasms—or abnormal growths
  • History of blood clots
  • History of breast cancer
  • History of heart attack
  • History of stroke
  • Liver impairment or disease
  • History of certain medical conditions—like protein C, protein S, or antithrombin deficiency—that raise your risk of blood clots
  • Severe allergic reaction to Activella or its components

What Other Medications Interact With Activella?

In general, CYP3A4 is a type of protein in the liver that breaks down Activella. Therefore, any medications that influence the way CYP3A4 works may also affect the amount of Activella medication in the body.

Medications—like Saint-John’s-wort for mood or Tegretol (carbamazepine) for seizures—are CYP3A4 inducers. So, they encourage CYP3A4 to quickly work and break down Activella. With fewer amounts of Activella in the body, the medication is also less effective.

On the other hand, medications—like an erythromycin antibiotic—are CYP3A4 inhibitors. These medications prevent CYP3A4 from working as well. Therefore, there is a higher amount of Activella in the body to cause serious side effects.

What Medications Are Similar?

There are many available medications that can help with relieving menopausal symptoms. These types of hormone therapy are available as oral tablets, patches, a cream, or a vaginal ring.

Hormonal therapy can also be available with a single hormone or a combination of estrogen and progestin. 

Activella is an oral hormone therapy with a combination of estradiol and norethindrone.

However, there are other oral hormonal therapies with various combinations of estrogen and progestin forms.

Some of these other oral hormonal therapies include:

  • Angeliq (estradiol and drospirenone)
  • FemHRT (ethinyl estradiol and norethindrone)
  • Jinteli (ethinyl estradiol and norethindrone)
  • Prefest (estradiol and norgestimate)
  • Premphase (conjugated estrogens and medroxyprogesterone)
  • Prempro (conjugated estrogens and medroxyprogesterone)

In addition to these oral combination hormone therapy options, there are also Amabelz and Mimvey.

Like Activella, both Amabelz and Mimvey contain estradiol and norethindrone.

With so many different choices, the following are some factors to consider while deciding on a product:

Estrogen dose: Since taking estrogen can raise the likelihood of blood clots, some people might prefer hormone therapy with low doses of estrogen.

Progestin type: There are different types of progestin, which mimic the naturally occurring sex hormone called progesterone. Some types might have less negative effects on blood pressure, triglycerides, and how the body breaks down and uses carbohydrates.

The best hormone therapy will vary by person. So, talking with your healthcare provider might help you sort through all the different choices.

Since all of these oral combination hormonal therapies are used to relieve menopause, they are not typically taken together. If you have any questions, also discuss them with your healthcare provider.

Frequently Asked Questions

  • Will I gain weight with Activella?

    Although weight gain is a common side effect of Activella, hormonal changes during menopause are also linked to weight gain.

    However, if you do struggle with your weight, know that there are healthy ways to stop gaining weight during menopause.

  • Can I get cancer with Activella?

    Breast cancer is a risk with long-term use of Activella. As a result, it’s important to take hormone therapy at the lowest effective dose for the shortest amount of time possible.

    Stay in touch with your healthcare provider every three to six months to help you weigh the benefits and risks of continuing hormone therapy.

  • Can I stop taking Activella cold turkey?

    Some people can stop hormone therapy cold turkey. For other people, however, slowly lowering the dose to discontinue the medication over time might be beneficial.

    The decision will be different depending on the person and symptoms. Discuss with your healthcare provider to help find the next best step for you.

How Can I Stay Healthy While Taking Activella?

Although menopause is a normal part of life, it can come with a lot of stressors, making hormonal changes and bothersome symptoms—like hot flashes, sweating, and weight gainunwelcome changes.

As you are going through menopause, remember to take care of yourself. Find ways to manage your stress. Also, consider consulting with a mental health professional to help with coping strategies to balance all the new changes in your life. 

Try to also stay physically active, such as by taking long walks, which might help you de-stress and meet your weight goals. If you cook, consider cooking healthy meals. If you’re traveling or vacationing, take part in active excursions.

Medical Disclaimer

Verywell Health's drug information is meant for educational purposes only and is not intended to replace medical advice, diagnosis, or treatment from a healthcare provider. Consult your healthcare provider before taking any new medication(s). IBM Watson Micromedex provides some of the drug content, as indicated on the page.

12 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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  2. MedlinePlus. Estrogen and progestin (hormone replacement therapy).

  3. National Cancer Institute. Estradiol/norethindrone acetate tablet.

  4. United States Department of Health & Human Services. Office on Women's Health. Menopause basics.

  5. United States Department of Health & Human Services. Office on Women's Health. Menopause symptoms and relief.

  6. Naumova I, Castelo-Branco C. Current treatment options for postmenopausal vaginal atrophyInt J Womens Health. 2018;10:387-395. Published 2018 Jul 31. doi:10.2147/IJWH.S158913

  7. National Institute on Aging. What is menopause?

  8. United States Department of Health & Human Services. Office on Women's Health. Menopause treatment.

  9. Dailymed. Label: Amabelz- estradiol and norethindrone acetate tablet.

  10. Dailymed. Label: Mimvey- estradiol and norethindrone acetate tablet, film coated.

  11. Endocrine Society. Treatment of the symptoms of menopause guideline resources.

  12. American Family Physician. Hormone therapy and other treatments of symptoms of menopause.

By Ross Phan, PharmD, BCACP, BCGP, BCPS
Ross is a writer for Verywell with years of experience practicing pharmacy in various settings. She is also a board-certified clinical pharmacist and the founder of Off Script Consults.