Estrace vs. Premarin: Differences, similarities, and which is better for you

Drug overview & main differences | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQ

If you experience menopausal symptoms, such as hot flashes, night sweats, sleep problems, and vaginal dryness, your healthcare provider might have mentioned hormone replacement therapy or estrogen therapy. Menopause symptoms occur when the body makes less estrogen, so medications that replace estrogen can help improve these symptoms, and also help prevent osteoporosis.

In women with a uterus, hormone therapy includes both estrogen and progesterone. In women with a uterus, estrogen alone increases the risk for endometrial cancer.

Women without a uterus (who have had a hysterectomy) do not need to take progesterone with estrogen. These women can use estrogen-only products such as Estrace or Premarin.

Estrace and Premarin are two brand-name medications indicated for the treatment of menopause symptoms. Both drugs are approved by the United States Food and Drug Administration (FDA). They are in a class of medications called estrogens and are also known as hormone replacement therapy. They are available in a variety of formulations, including creams and tablets. Although both Estrace and Premarin contain estrogen, they are not exactly the same. Continue reading to learn more about Estrace and Premarin.

What are the main differences between Estrace and Premarin?

Estrace is available in brand and generic form and contains the ingredient estradiol. Estrace is available as a vaginal estrogen cream, and also as an oral tablet.

Premarin is available as a brand-name drug only. It contains conjugated estrogens, purified from pregnant mares’ urine (hence the name Premarin- PREgnant MARes urINe). Premarin is available as a vaginal estrogen cream, oral tablet, or injection.

Main differences between Estrace and Premarin
	Estrace	Premarin
Drug class	Estrogens/hormone replacement therapy	Estrogens/hormone replacement therapy
Brand/generic status	Brand and generic	Brand
What is the generic name?	Estradiol	Conjugated estrogens
What form(s) does the drug come in?	Vaginal cream, oral tablet	Vaginal cream, oral tablet, injection
What is the standard dosage?	Cream: 2 to 4 grams vaginally daily for 1-2 weeks, then gradually reduce to a maintenance dose of 1 gram 1-3 times per week Tablets: varies	Cream: 0.5 grams vaginally twice a week Tablets: varies
How long is the typical treatment?	Varies	Varies
Who typically uses the medication?	Postmenopausal women, occasionally in men for certain indications (see below)	Postmenopausal women, occasionally in men for certain indications (see below)

Conditions treated by Estrace and Premarin

Estrace cream and Premarin cream treat moderate to severe symptoms of vaginal and vulvar atrophy (thinning, drying, and inflammation) due to menopause.

In the tablet form, Estrace and Premarin treat various other conditions listed in the chart below.

Condition	Estrace	Premarin
Moderate to severe symptoms of vulvar/vaginal atrophy due to menopause	Yes (cream)	Yes (cream)
Treatment of hypoestrogenism due to hypogonadism, castration, or primary ovarian failure	Yes (tablet)	Yes (tablet)
Treatment of breast cancer (for palliation only) in certain women and men with metastatic disease	Yes (tablet)	Yes (tablet)
Treatment of advanced androgen-dependent carcinoma of the prostate (for palliation only)	Yes (tablet)	Yes (tablet)
Prevention of postmenopausal osteoporosis for women at high risk, when non-estrogen medications are not appropriate	Yes (tablet)	Yes (tablet)
Treatment of atrophic vaginitis and kraurosis vulvae	Off-label	Yes (cream)
Treatment of moderate to severe dyspareunia (painful intercourse) due to menopause	Off-label	Yes (cream)
Treatment of moderate to severe vasomotor symptoms due to menopause	Yes (tablet)	Yes (tablet)

Is Estrace or Premarin more effective?

Studies show that when comparing estrogen products, estradiol (the ingredient in Estrace) and conjugated estrogens (the ingredient in Premarin) are equally effective in treating menopause symptoms. Vaginal creams are effective and well-tolerated.

Your healthcare provider can determine which medication is appropriate for you, considering your symptoms, medical conditions, and medical history.

Coverage and cost comparison of Estrace vs. Premarin

Insurance and Medicare prescription plans typically cover Estrace and Premarin.

A typical generic Estrace prescription is for a tube of cream and costs about $36 if you pay out of pocket, but using a free SingleCare coupon can bring the price down to as little as $6.

A typical prescription for a tube Premarin costs about $250 out-of-pocket. A SingleCare card can bring the price down to as low as $198.

As plans vary, contact your insurance provider for coverage details.

	Estrace	Premarin
Typically covered by insurance?	Yes	Yes
Typically covered by Medicare Part D?	Yes	Yes
Quantity	1 tube	1 tube
Typical Medicare copay	$1-$36	$2-$451
SingleCare cost	$6+	$198+

Common side effects of Estrace vs. Premarin

The most common side effects of Estrace and Premarin cream include application site reactions like itching, discharge, uterine bleeding, and inflammation. Additionally, headache and pelvic pain may occur. The percentage of side effects is not included in the prescribing information for Estrace.

Common side effects of Estrace and Premarin in the tablet form are more systemic. Some of these side effects include abdominal or back pain, weakness, swelling, headache, constipation, gas, nausea, weight gain, depression, nervousness, dizziness, breast tenderness/pain/changes, and vaginal discharge, bleeding, or yeast infection.

This is not a full list of side effects.  Other adverse effects may occur. Consult your healthcare provider to discuss what side effects to expect, and how to address them.

	Estrace cream		Premarin cream
Side effect	Applicable?	Frequency	Applicable?	Frequency
Headache	Yes	% not reported	Yes	3-5%*
Pelvic pain	Yes	% not reported	Yes	4%
Itching	Yes	% not reported	Yes	1-2%
Vaginal discharge	No	–	Yes	3-4%
Vaginal bleeding	Yes	% not reported	Yes	1-2%
Vaginal inflammation	Yes	% not reported	Yes	1-2%
Vaginal infection/yeast infection	Yes	% not reported	Yes	3-4%

*depends on dosage frequency
Source: DailyMed (Estrace cream), DailyMed (Premarin cream)

Drug interactions of Estrace vs. Premarin

Estrace or Premarin may be affected by certain drugs that are metabolized by an enzyme called cytochrome-p 450 3A4. Drugs that inhibit the enzyme may slow down the body’s processing of Estrace or Premarin, meaning Estrace or Premarin might stay in the body longer, causing more side effects. Also, drugs that induce the enzyme may cause the body to process Estrace or Premarin more quickly, making it less effective. Consult your healthcare provider regarding possible drug interactions.

Drug	Drug class	Estrace	Premarin
Clarithromycin Erythromycin Grapefruit juice Itraconazole Ketoconazole Ritonavir	CYP3A4 enzyme inhibitors	Possible	Possible
Carbamazepine Phenobarbital Rifampin St. John’s wort	CYP3A4 enzyme inducers	Possible	Possible

Warnings of Estrace and Premarin

Estrace and Premarin have a boxed warning, which is the strongest warning required by the FDA. Because systemic absorption can occur with Estrace or Premarin cream, the warnings apply to all formulations.

Estrogen alone:

• Using estrogen alone (without a progestin) in a woman with a uterus increases the risk of endometrial cancer. Adding progestin to estrogen treatment can lower the risk of endometrial cancer (but can increase the risk of breast cancer). Postmenopausal women with abnormal bleeding should be tested to rule out malignancy.
• Do not use estrogen alone to prevent heart disease or dementia. The Women’s Health Initiative (WHI) study found an increased risk of stroke and DVT (deep vein thrombosis, or a blood clot in the leg) in postmenopausal women who took estrogen alone (without progestin).
• The study also showed an increased risk of dementia in postmenopausal women who took estrogen alone.

Estrogen plus progestin:

• Do not use estrogen plus progestin to prevent heart disease or dementia. The WHI study found higher risks of DVT, PE (pulmonary embolism), stroke, and MI in postmenopausal women who took estrogen plus progestin. The study also showed a higher risk of developing dementia in postmenopausal women who took estrogen plus progestins.
• The WHI study also showed an increased risk of invasive breast cancer with estrogen plus progestin.

Therefore, estrogens, regardless of whether they are prescribed with or without progestins, should be prescribed at the lowest dose and for the shortest period of time. Talk with your healthcare provider about the risks vs benefits of various types of hormone replacement therapy.

Your doctor will give you medical advice on screening. All women should have a yearly breast exam by a healthcare professional and do a monthly self-exam. All women should also have mammography based on age, risk factors, and history.

Other warnings of Estrace and Premarin follow.

Do not use Estrace or Premarin if you have:

• Undiagnosed abnormal bleeding
• Breast cancer (known, suspected, or history)
• Estrogen-dependent neoplasia (known or suspected)
• DVT or pulmonary embolism (active or history)
• Active or history of thromboembolic disease (stroke, MI)
• Previous anaphylactic reaction to estrogen
• Liver disease
• Thrombophilic disorders
• Pregnancy (known or suspected)

Combination hormone therapy (estrogen plus progestin) may increase the risk of ovarian cancer.

Postmenopausal women who take estrogen have an increase in the risk of gallbladder disease requiring surgery.

In people who take estrogens, visual problems have occurred. Seek immediate medical treatment if you have loss of vision (partial or complete), double vision, eye bulging, or migraine.

In rare cases, allergic reactions have occurred. If you have hives, itching, difficulty breathing, vomiting, or swelling of the face, lips, tongue, hands, or feet, seek emergency medical care right away. Estrogen medication may worsen angioedema symptoms in women with hereditary angioedema.

Talk to your healthcare provider about these risks before taking Estrace or Premarin, to see if the medicine is safe for you.

Frequently asked questions about Estrace vs. Premarin

What is Estrace?

Estrace is a hormone replacement medication that contains estradiol. It is used for a variety of indications, most often for symptoms of menopause. Estrace is available as an intravaginal cream as well as an oral tablet.

What is Premarin?

Premarin is also a hormone replacement drug. Premarin contains conjugated estrogens. It is used for several indications, most often for menopause symptoms. Premarin is available as an oral tablet, intravaginal cream, and injection.

Are Estrace and Premarin the same?

Estrace and Premarin are similar, but not exactly the same. The information above outlines the differences between the two medications.

Is Estrace or Premarin better?

Both medications are effective in treating menopause symptoms, however, these drugs do come with side effects and risks. Talk with your healthcare provider to determine if Estrace or Premarin is appropriate for you.

Can I use Estrace or Premarin while pregnant?

No. Neither medication should be used in pregnancy.

Can I use Estrace or Premarin with alcohol?

Drinking alcohol in combination with Estrace or Premarin can increase your risk for breast cancer. Consult your healthcare professional for guidance on alcohol use with any medical conditions you have.

What is the best alternative to Premarin?

Estrace is a similar alternative to Premarin. Other medications containing estrogen include the Vivelle Dot Patch, Climara Patch, or vaginal estrogen in the form of Vagifem vaginal tablets (vaginal tablets applied with a vaginal applicator) or Estring Vaginal Ring. Talk to your healthcare provider to see if one of these medications is appropriate for you.

Are estrogen and estradiol the same thing?

Estradiol is a form of estrogen, a female hormone. All estradiol products are estrogen. However, there are other forms of estrogen than just estradiol. For example, conjugated estrogens (Premarin) is another form of estrogen.

Does Premarin cause dementia?

Premarin (and Estrace) has a boxed warning about dementia. The WHI Memory Study mentioned above found an increased risk of developing dementia in postmenopausal women who took estrogen alone or estrogen with a progestin. Therefore, the prescribing information recommends that estrogen, whether taken alone or with progestin, should be prescribed at the lowest dose and for the shortest time.

Does Estrace increase estrogen levels?

Estrace (and Premarin) increase estrogen levels. Even in the vaginal form, there is systemic absorption, and estrogen levels increase. Your healthcare provider can determine which product is most appropriate for you.