Estradiol/Norethindrone is a combination hormone replacement therapy (HRT) that contains an estrogen and a progestin, prescribed to treat moderate-to-severe menopause symptoms and prevent postmenopausal osteoporosis.

If your doctor has mentioned this medication — or you've seen it listed as Activella, Amabelz, Lopreeza, Mimvey, or CombiPatch — this guide covers everything you need to know, from what it's used for to how much it costs.

What Is Estradiol/Norethindrone?

Estradiol/Norethindrone (full generic name: Estradiol and Norethindrone Acetate) is a sex hormone combination medication. It combines two hormones:

• Estradiol — a synthetic form of estrogen, the primary female sex hormone that declines during menopause
• Norethindrone Acetate — a progestin (synthetic progesterone) that protects the uterine lining from overgrowth caused by estrogen

Brand Names

• Activella — oral tablets, manufactured by Novo Nordisk
• Amabelz — oral tablets
• Lopreeza — oral tablets
• Mimvey — oral tablets
• CombiPatch — transdermal patch

Generic versions are widely available for the oral tablet. The medication is not a controlled substance and does not require special DEA prescribing.

FDA Approval

Activella was approved by the FDA for the treatment of menopause symptoms and prevention of osteoporosis. Generic versions have since been approved by multiple manufacturers including Amneal and Teva.

What Is Estradiol/Norethindrone Used For?

Estradiol/Norethindrone is FDA-approved for three main uses:

1. Moderate-to-severe vasomotor symptoms (hot flashes and night sweats) — This is the most common reason it's prescribed. When estrogen levels drop during menopause, many women experience hot flashes, night sweats, and sleep disruption. Estradiol/Norethindrone replaces some of the lost estrogen to relieve these symptoms.
2. Moderate-to-severe vulvar and vaginal atrophy — Declining estrogen can cause vaginal dryness, irritation, and pain during intercourse. This medication helps restore vaginal tissue health.
3. Prevention of postmenopausal osteoporosis — Estrogen plays a key role in maintaining bone density. Estradiol/Norethindrone can help prevent bone loss in postmenopausal women at risk for osteoporosis.

Off-label uses include hormone replacement for premature ovarian insufficiency and hypogonadism in women.

Important: This medication is intended for women who still have a uterus. The Norethindrone Acetate component protects the uterine lining from the overgrowth (endometrial hyperplasia) that estrogen alone can cause. Women who have had a hysterectomy typically use estrogen-only therapy instead.

How Is Estradiol/Norethindrone Taken?

Oral Tablets

The most common formulation is a once-daily oral tablet. Available strengths include:

• 1 mg Estradiol / 0.5 mg Norethindrone Acetate — the standard dose
• 0.5 mg Estradiol / 0.1 mg Norethindrone Acetate — the low dose

Take one tablet by mouth at the same time each day, with or without food. Your doctor will typically start you on the lowest effective dose.

Transdermal Patch (CombiPatch)

CombiPatch is applied to a clean, dry area of the lower abdomen and replaced twice weekly (every 3 to 4 days). Available in two strengths:

• 0.05 mg/day Estradiol / 0.14 mg/day Norethindrone Acetate
• 0.05 mg/day Estradiol / 0.25 mg/day Norethindrone Acetate

The patch may be preferred by women who experience nausea with oral tablets, or who have certain liver or gallbladder concerns, since the transdermal route bypasses the liver.

General Guidelines

• Use the lowest effective dose for the shortest duration consistent with your treatment goals
• Take it consistently — skipping doses can cause breakthrough bleeding and reduced symptom relief
• Do not stop abruptly without talking to your doctor

Who Should Not Take Estradiol/Norethindrone?

This medication is not safe for everyone. You should not take Estradiol/Norethindrone if you have:

• Undiagnosed abnormal genital bleeding
• Known or suspected breast cancer, or a history of breast cancer
• Known or suspected estrogen-dependent tumors
• Active or history of blood clots (deep vein thrombosis or pulmonary embolism)
• Active or history of arterial thromboembolic disease (stroke or heart attack)
• Known liver impairment or disease
• Known clotting disorders (protein C, protein S, or antithrombin deficiency)
• Pregnancy
• Known severe allergic reaction to the medication

For a detailed look at risks and warnings, read our guide on Estradiol/Norethindrone side effects.

How Much Does Estradiol/Norethindrone Cost?

Cost varies significantly based on whether you use the brand name or generic, and whether you have insurance:

• Generic oral tablets (without insurance): $50 to $200+ per month at retail price. With a discount card like GoodRx, prices can drop to as low as $15 to $50 per month for a 30-day supply.
• Brand-name Activella: $50 to $200+ per month without insurance.
• CombiPatch: Generally more expensive than oral tablets, especially during shortages.
• With insurance: Most commercial insurance plans and Medicare Part D cover generic Estradiol/Norethindrone as a Tier 2 or Tier 3 medication. Your copay will depend on your specific plan.

For tips on reducing your costs, see our complete guide to saving money on Estradiol/Norethindrone. If you're uninsured or underinsured, Novo Nordisk offers a patient assistance program — call 1-866-668-6336 for details.

Final Thoughts

Estradiol/Norethindrone is a well-established combination hormone therapy that helps millions of women manage menopause symptoms and protect their bone health. It comes in oral tablets and a transdermal patch, with generic options that make it affordable for most patients.

If you're considering this medication, talk to your doctor about whether it's right for your situation. And if you need help finding it at a pharmacy near you, Medfinder can show you which pharmacies have it in stock.

Want to understand how it works in your body? Read How Does Estradiol/Norethindrone Work?