Side effects estrace cream

Contents

Estrace (Vaginal)

Generic Name: estrogen (Vaginal route)

Commonly used brand name(s)

In the U.S.

  • Estrace
  • Estring
  • Femring
  • Imvexxy
  • Ortho Dienestrol
  • Premarin
  • Premarin Vaginal
  • Vagifem

Available Dosage Forms:

  • Cream
  • Insert, Extended Release
  • Capsule, Liquid Filled
  • Tablet

Uses for Estrace

Estrogens are hormones produced by the body. Among other things, estrogens help develop and maintain female organs.

When your body is in short supply of this hormone, replacing it can ease the uncomfortable changes that occur in the vagina, vulva (female genitals), and urethra (part of the urinary system). Conditions that are treated with vaginal estrogens include a genital skin condition (vulvar atrophy), inflammation of the vagina (atrophic vaginitis), and inflammation of the urethra (atrophic urethritis).

Estrogens work partly by increasing a normal clear discharge from the vagina and making the vulva and urethra healthy. Using or applying an estrogen relieves or lessens:

  • Dryness and soreness in the vagina
  • Itching, redness, or soreness of the vulva
  • Feeling an urge to urinate more often then is needed or experiencing pain while urinating
  • Pain during sexual intercourse

When used vaginally or on the skin, most estrogens are absorbed into the bloodstream and cause some, but not all, of the same effects as when they are taken by mouth. Estrogens used vaginally at very low doses for treating local problems of the genitals and urinary system will not protect against osteoporosis or stop the hot flushes caused by menopause.

Estrogens for vaginal use are available only with your doctor’s prescription.

Before using Estrace

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to medicines in this group or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Estrogen vaginal cream is not indicated in children. Studies have not been conducted.

Geriatric

Elderly women greater than 65 years of age may have an increased risk of certain side effects during treatment, especially stroke, invasive breast cancer, and memory problems.

Pregnancy

Estrogens should not be used during pregnancy, since an estrogen called diethylstilbestrol (DES) that is no longer taken for hormone replacement has caused serious birth defects in humans and animals.

Breastfeeding

Use of this medicine is not recommended in nursing mothers. Estrogens pass into the breast milk and may decrease the amount and quality of breast milk. Caution should be exercised in mothers who are using estrogen and breast-feeding.

Interactions with medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking any of these medicines, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using medicines in this class with any of the following medicines is not recommended. Your doctor may decide not to treat you with a medication in this class or change some of the other medicines you take.

  • Dasabuvir
  • Ombitasvir
  • Paritaprevir
  • Ritonavir
  • Tranexamic Acid

Using medicines in this class with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Aprepitant
  • Boceprevir
  • Bosentan
  • Bupropion
  • Carbamazepine
  • Ceritinib
  • Conivaptan
  • Dabrafenib
  • Darunavir
  • Dexamethasone
  • Donepezil
  • Encorafenib
  • Enzalutamide
  • Fosaprepitant
  • Fosnetupitant
  • Fosphenytoin
  • Griseofulvin
  • Isotretinoin
  • Lesinurad
  • Lixisenatide
  • Lumacaftor
  • Mitotane
  • Modafinil
  • Nafcillin
  • Netupitant
  • Nevirapine
  • Oxcarbazepine
  • Phenobarbital
  • Phenytoin
  • Pitolisant
  • Pixantrone
  • Prednisone
  • Primidone
  • Rifabutin
  • Rifampin
  • St John’s Wort
  • Sugammadex
  • Theophylline
  • Topiramate
  • Valproic Acid

Interactions with food/tobacco/alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other medical problems

The presence of other medical problems may affect the use of medicines in this class. Make sure you tell your doctor if you have any other medical problems, especially:

  • Asthma or
  • Epilepsy or
  • Heart problems or
  • Kidney problems or
  • Migraine headaches—Estrogens may worsen these conditions.
  • Blood clotting problems—Although worsening of a blood clotting condition is unlikely, some doctors do not prescribe vaginal estrogens for patients with blood clotting problems or a history of these problems.
  • Breast cancer (active, suspected, or past history)—Estrogens should not be used.
  • Certain cancers, including cancers of the breast, bone, or uterus (active or suspected)—Estrogens may interfere with the treatment of breast or bone cancer or worsen cancer of the uterus when these conditions are present.
  • Cholestatic jaundice (flow of bile from the liver is blocked), past history—Caution should be used when this condition is present.
  • Diabetes mellitus (sugar diabetes)—Estrogens may alter your body’s response to sugar in your diet.
  • Endometriosis or
  • Fibroid tumors of the uterus—Estrogens may worsen endometriosis or increase the size of fibroid tumors.
  • Gallbladder problems (gallstones)—Estrogens may increase your chance of getting a gallbladder attack.
  • Heart attack or
  • Stroke (active or past history)—Estrogens should not be used.
  • Hepatic hemangioma (noncancerous tumors of the liver)—Estrogens may worsen this medical problem.
  • High blood pressure—Estrogens may worsen this medical problem.
  • Hypercalcemia (too much calcium in your blood)—Estrogens may worsen this medical problem.
  • Hypertriglyceridemia (too much triglycerides in your blood)—Estrogens may increase your chance of getting pancreatitis or other side effects.
  • Hypocalcemia (too little calcium in your blood)—Your doctor should treat the low calcium in your blood before starting estrogen therapy.
  • Irritation or infection of the vagina—Usually estrogens decrease infections or irritation of the vagina, but sometimes these conditions may become worse.
  • Liver disease or
  • Liver problems—Estrogens should not be used.
  • Lupus erythematosus, systemic (SLE or lupus)—Estrogens may worsen this medical problem.
  • Physical problems within the vagina, such as narrow vagina, vaginal stenosis, or vaginal prolapse—Estradiol vaginal insert or ring may be more likely to slip out of place or cause problems, such as irritation of the vagina.
  • Porphyria—Estrogens may worsen this medical problem.
  • Thyroid problems (underactive thyroid)—Estrogens may alter your body’s response to your thyroid medication. Your doctor may alter the amount of thyroid replacement that you take while on estrogen therapy.
  • Vision changes, sudden onset including
  • Bulging eyes or
  • Double vision or
  • Migraine headache or
  • Vision loss, partial or complete—Estrogens may cause these problems. Tell your doctor if you have had any of these problems.
  • Unusual genital or vaginal bleeding of unknown causes—Use of estrogens may delay diagnosis or worsen the condition. The reason for the bleeding should be determined before estrogens are used.

Proper use of estrogen

This section provides information on the proper use of a number of products that contain estrogen. It may not be specific to Estrace. Please read with care.

Vaginal estrogen products usually come with patient directions. Read them carefully before using this medicine.

Wash your hands before and after using the medicine. Also, keep the medicine out of your eyes. If this medicine does get into your eyes, wash them out immediately, but carefully, with large amounts of tap water. If your eyes still burn or are painful, check with your doctor.

Use this medicine only as directed. Do not use more of it and do not use it for a longer time than your doctor ordered. It can take up to 4 months to see the full effect of the estrogens. Your doctor may reconsider continuing your estrogen treatment or may lower your dose several times within the first one or two months, and every 3 to 6 months after that. Sometimes a switch to oral estrogens may be required for added benefits or for higher doses. When using the estradiol vaginal insert or ring, you will need to replace it every 3 months or remove it after 3 months.

For vaginal creams or suppositories:

  • Vaginal creams and some vaginal suppositories are inserted with a plastic applicator. Directions for using the applicator are supplied with your medicine. If you do not see your dose marked on the applicator, ask your health care professional for more information.
  • To fill the applicator for cream dosage forms:
    • Screw the applicator onto the tube.
    • Squeeze the medicine into the applicator slowly until it is measured properly.
    • Remove the applicator from the tube. Replace the cap on the tube.
  • To fill the applicator for suppository dosage form:
    • Place the suppository into the applicator.
  • To place the dose using the applicator for cream and suppository dosage forms:
    • Relax while lying on your back with your knees bent or stand with one foot on a chair.
    • Hold the full applicator in one hand. Slide the applicator slowly into the vagina. Stop before it becomes uncomfortable.
    • Slowly press the plunger until it stops.
    • Withdraw the applicator. The medicine will be left behind in the vagina.
  • To care for the applicator for cream and suppository dosage forms:
    • Clean the applicator after use by pulling the plunger out of the applicator and washing both parts completely in warm, soapy water. Do not use hot or boiling water.
    • Rinse well.
    • After drying the applicator, replace the plunger.

For vaginal insert or ring dosage form:

  • To place the vaginal insert:
    • Relax while lying on your back with your knees bent or stand with one foot on a chair.
    • Pinch or press the sides of the vaginal insert together, between your forefinger and middle finger.
    • With one hand, part the folds of skin around your vagina.
    • Slide the vaginal insert slowly into the upper third of your vagina. Stop before it becomes uncomfortable. The exact location is not too important but it should be comfortable.
    • If it seems uncomfortable, then carefully push the vaginal insert higher into the vagina.
  • To remove the vaginal insert:
    • Stand with one foot on a chair.
    • Slide one finger into the vagina and hook it around the closest part of the vaginal insert.
    • Slowly pull the vaginal insert out.
    • Dispose of the vaginal insert by wrapping it up and throwing it into the trash. Do not flush it down the toilet.

Dosing

The dose medicines in this class 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 these medicines. 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 conjugated estrogens

  • For vaginal dosage form (cream):
    • For treating inflammation of the vagina (atrophic vaginitis):
      • Adults—At first, 0.5 gram (g) of conjugated estrogens inserted into the vagina once a day or as directed by your doctor to achieve the lowest dose possible. Usually your doctor will want you to use this medicine for only three weeks of each month (three weeks on and one week off). Your doctor may increase your dose as needed. However, the dose is usually not more than 2 grams per day.
    • For treating a genital skin condition (vulvar atrophy):
    • Adults—0.5 gram (g) of conjugated estrogens inserted into the vagina two times per week. Usually your doctor will want you to use this medicine for only three weeks of each month (three weeks on and one week off).
    For estradiol

  • For vaginal dosage form (cream):
    • For treating a genital skin condition (vulvar atrophy) and inflammation of the vagina (atrophic vaginitis):
      • Adults—200 to 400 micrograms (mcg) of estradiol (two to four grams of cream) inserted into the vagina once a day for one to two weeks, decreasing the dose by one half over two and four weeks. After four weeks, your doctor will probably ask you to use the medicine less often, such as 100 mcg (one gram of cream) one to three times a week and for only three weeks of each month (three weeks on and one week off).
  • For vaginal dosage form (insert or ring):
    • For treating a genital skin condition (vulvar atrophy), inflammation of the vagina (atrophic vaginitis) in postmenopausal women, and inflammation of the urethra (urethritis) in postmenopausal women:
      • Adults—One insert containing 2 to 24.8 milligrams (mg) of estradiol inserted into the vagina every three months. The insert will slowly release estradiol at a rate of 7.5 to 100 micrograms (mcg) every twenty-four hours with continuous use.

    For estrone

  • For vaginal dosage form (cream):
    • For treating a genital skin condition (vulvar atrophy) and inflammation of the vagina (atrophic vaginitis) in postmenopausal women:
      • Adults—2 to 4 milligrams (mg) of estrone (two to four grams of cream) inserted into the vagina once a day or as directed by your doctor.
  • For vaginal dosage form (suppository):
    • For treating a genital skin condition (vulvar atrophy) and inflammation of the vagina (atrophic vaginitis) in postmenopausal women:
      • Adults—250 to 500 micrograms (mcg) inserted into the vagina once a day or as directed by your doctor.

Missed dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

When using the suppository or cream several times a week: If you miss a dose of this medicine and remember it within 1 or 2 days of the missed dose, use the missed dose as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

When using the cream or suppositories more than several times a week: If you miss a dose of this medicine, use it as soon as possible if remembered within 12 hours of the missed dose. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Do not keep outdated medicine or medicine no longer needed.

Precautions while using Estrace

It is very important that your doctor check your progress at regular visits to make sure this medicine does not cause unwanted effects. Plan on going to see your doctor every year, but some doctors require visits more often.

It is not yet known whether the use of vaginal estrogens increases the risk of breast cancer in women. It is very important that you check your breasts on a regular basis for any unusual lumps or discharge. Report any problems to your doctor. You should also have a mammogram (x-ray picture of the breasts) done if your doctor recommends it.

It is important that you have a regular pelvic exam (pap smear). Your doctor will tell you how often this exam should be done.

Talk to your doctor if you have high blood pressure, high cholesterol (fats in the blood), or diabetes, use tobacco, or are overweight. You may have a higher risk for getting heart disease.

Although the chance is low, use of estrogen may increase your chance of getting cancer of the ovary or uterus (womb). Regular visits to your health professional can help identify these serious side effects early.

If you think that you may be pregnant, stop using the medicine immediately and check with your doctor.

Tell the doctor in charge that you are using this medicine before having any laboratory test, because some test results may be affected.

For vaginal creams or suppositories:

  • Avoid using latex condoms, diaphragms, or cervical caps for up to 72 hours after using estrogen vaginal creams. Certain estrogen products may contain oils in the creams that can weaken latex (rubber) products and cause condoms to break or leak, or cervical caps or diaphragms to wear out sooner. Check with your health care professional to make sure the vaginal estrogen product you are using can be used with latex devices.
  • This medicine is often used at bedtime to increase effectiveness through better absorption.
  • Vaginal creams or suppositories will melt and leak out of the vagina. A minipad or sanitary napkin will protect your clothing. Do not use tampons (like those used for menstrual periods) since they may soak up the medicine and make the medicine less effective.
  • Avoid exposing your male sexual partner to your vaginal estrogen cream or suppository by not having sexual intercourse right after using these medicines. Your male partner might absorb the medicine through his penis if it comes in contact with the medicine.

For estradiol vaginal inserts or rings:

  • Contact your doctor if you have problems removing your vaginal insert.
  • It is not necessary to remove the vaginal insert for sexual intercourse unless you prefer to remove it.
  • If you do take it out, or if it accidentally slips or comes out of the vagina, you can replace the vaginal insert in the vagina after washing it with lukewarm water. Never use hot or boiling water.
  • If it slips down, gently push it upwards and back into place.
  • Replace the vaginal insert every 3 months.
  • Talk to your doctor on a regular basis about how long to use the vaginal insert.

Estrace side effects

The risk of any serious adverse effect is unlikely for most women using low doses of estrogens vaginally. Even women with special risks have used vaginal estrogens without problems.

Check with your doctor immediately if any of the following side effects occur:

Less common

  • Breast pain
  • enlarged breasts
  • itching of the vagina or genitals
  • headache
  • nausea
  • stinging or redness of the genital area
  • thick, white vaginal discharge without odor or with a mild odor

Rare

  • Feeling of vaginal pressure (with estradiol vaginal insert or ring)
  • unusual or unexpected uterine bleeding or spotting
  • vaginal burning or pain (with estradiol vaginal insert or ring)

Incidence not known

  • Diarrhea
  • dizziness
  • fast heartbeat
  • feeling faint
  • fever
  • hives
  • hoarseness
  • itching
  • joint pain, stiffness, or swelling
  • muscle pain
  • rash
  • shortness of breath
  • skin redness
  • swelling of eyelids, face, lips, hands, or feet
  • tightness in the chest
  • trouble with breathing or swallowing
  • vomiting
  • wheezing

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

  • Abdominal or back pain
  • clear vaginal discharge (usually means the medicine is working)

Incidence not known

  • Acne
  • enlargement of penis or testes
  • growth of pubic hair
  • rapid increase in height
  • swelling of the breasts or breast soreness in males

Also, many women who are using estrogens with a progestin (another female hormone) will start having monthly vaginal bleeding that is similar to menstrual periods. This effect will continue for as long as the medicine is taken. However, monthly bleeding will not occur in women who have had the uterus removed by surgery (hysterectomy).

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Estrace Side Effects

Visit your doctor or health care professional for regular checks on your progress. You will need a regular breast and pelvic exam and Pap smear while on this medicine. You should also discuss the need for regular mammograms with your health care professional, and follow his or her guidelines for these tests.

This medicine can make your body retain fluid, making your fingers, hands, or ankles swell. Your blood pressure can go up. Contact your doctor or health care professional if you feel you are retaining fluid.

If you have any reason to think you are pregnant, stop taking this medicine right away and contact your doctor or health care professional.

Smoking increases the risk of getting a blood clot or having a stroke while you are taking this medicine, especially if you are more than 35 years old. You are strongly advised not to smoke.

If you wear contact lenses and notice visual changes, or if the lenses begin to feel uncomfortable, consult your eye doctor or health care professional.

This medicine can increase the risk of developing a condition (endometrial hyperplasia) that may lead to cancer of the lining of the uterus. Taking progestins, another hormone drug, with this medicine lowers the risk of developing this condition. Therefore, if your uterus has not been removed (by a hysterectomy), your doctor may prescribe a progestin for you to take together with your estrogen. You should know, however, that taking estrogens with progestins may have additional health risks. You should discuss the use of estrogens and progestins with your health care professional to determine the benefits and risks for you.

If you are going to have surgery, you may need to stop taking this medicine. Consult your health care professional for advice before you schedule the surgery.

Confusion as EU Advice on Vaginal Estradiol Differs from US

A recent statement from an EU panel restricting use of “high-strength” estradiol vaginal creams to just 4 weeks has caused some confusion, but also illustrates actual differences between the European and US approaches to regulating the products.

The October 4 statement said that the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) “recommended limiting the use of high-strength creams containing 100 micrograms/gram (0.01%) of estradiol to a single treatment period of up to 4 weeks,” as reported by Medscape Medical News.

The advice, which reconfirms a 2014 recommendation, “is intended to minimize the risk of side effects such as blood clots, strokes, and certain types of cancer caused by estradiol absorbed into the bloodstream from creams applied inside the vagina to treat symptoms of vaginal atrophy in women who have been through menopause.”

In response a week later, the North American Menopause Society (NAMS) posted a statement to its members saying that the EMA PRAC recommendation “is not evidence-based.”

Moreover, the NAMS statement, authored by NAMS medical director Stephanie S. Faubion, MD, MBA, says the PRAC move “fails to recognize that genitourinary syndrome of menopause (GSM) is a chronic, progressive condition; symptoms do not resolve with time or short-term treatment.”

“This warning from the European Medicines Agency is likely to result in women avoiding a safe, effective, and much-needed treatment for this common condition. Untreated GSM can have a devastating effect on vulvovaginal health and women’s self-image, quality of life, and intimate relationships,” the NAMS adds.

Both organizations acknowledged to Medscape Medical News that the product advice or labeling on vaginal estrogen creams in the respective markets could cause confusion among prescribers and inadvertently lead to less women receiving this medication for GSM.

In the US, all local vaginal estrogen creams have a Food and Drug Administration (FDA) label warning about side effects; Faubion said NAMS is working with the agency to get this removed because NAMS doesn’t feel it is needed for locally applied vaginal creams.

Meanwhile, the EMA says it is making clear the distinction between low-dose and high-dose estradiol creams on respective product labels, so that doctors there can clearly distinguish between these two kinds of medications.

EMA Says Recommendation Only Applies to High-Strength Creams

Queried by Medscape Medical News, an EMA representative clarified that the PRAC recommendation applies solely to use of “high-strength creams containing 100 micrograms/gram (0.01% w/w) of estradiol only.”

It does not apply to lower-strength products such as Vagifem (Novo Nordisk) tablets , Estring (Pfizer) , Imvexxy (TherapeuticsMD) , or other comparable low-dose vaginal estrogen cream formulations.

Regarding the high-strength products, the EMA spokesperson said: “EMA’s scientific recommendations are fully evidence-based; the evidence considered by EMA’s scientific committees is described in the assessment report, which is transparently published on our website.”

“NAMS’ statement that EMA’s ‘advice is not evidence based’ is therefore strongly refuted,” the EMA spokesperson said. “This scientific recommendation is not new and all scientific evidence can be found in the initial review in 2014, where the whole issue was previously discussed.”

The EMA representative continued: “Systemic absorption has been demonstrated with these medicinal products…The concentration of estradiol in blood after administration has been shown to be above the normal menopausal range for estradiol with these higher-strength topical products.

“Therefore, a restriction of the duration of use was necessary, to safeguard women’s health against side effects due to systemic exposure with estradiol.”

The PRAC did take into consideration the chronic nature of the disease, advising that if symptoms persist beyond 4 weeks then alternative therapies should be considered, such as a low-dose topical estradiol.

“High” Dose vs “Low” Dose Is Artificial Concept With Estradiol Cream

But Faubion, who also directs the Mayo Clinic Center for Women’s Health in Rochester, Minnesota, told Medscape Medical News that NAMS doesn’t recognize the “high-dose” vs “low-dose” distinction “because it is artificial and driven by the amount one puts in the vagina. You can turn a cream into a ‘low dose’ by using a smaller amount, which is what the common practice in the US is.”

Therefore, she said, “it doesn’t make any sense to recommend against the use of a vaginal estrogen product simply because the dose used could be high enough to generate systemic levels.

“This is a matter of prescribing practices and educating patients and clinicians on the dose…needed to manage symptoms, which is often far less than was originally approved and is on the package label.”

But even beyond that, Faubion asserts, “There are no data to support any adverse effects related to any vaginal estrogen product designed to treat /GSM, including estradiol cream, and imposing such a restriction will no doubt lead to fewer women receiving therapy for this already under-recognized and undertreated common condition.”

All Vaginal Estradiol Creams in US Carry Boxed Warning

In Europe, the PRAC-defined “high-strength” estradiol cream products are authorized only in Austria, Bulgaria, Croatia, Czech Republic, Estonia, Germany, Hungary, Latvia, Lithuania, and Slovakia under the trade names Linoladiol, Linoladiol N, Linoladiol Estradiol, Estradiol Wolff, and Montadiol.

In the United States, the only such product on the market that meets the EMA PRAC definition of “high-strength” is Estrace (Allergan; estradiol vaginal cream, USP, 0.01%), for which each gram contains 0.1 mg (100 mcg) estradiol per gram of nonliquifying base, an FDA representative told Medscape Medical News.

However, the FDA does not advise a 4-week restriction on use of Estrace or any vaginal cream.

Instead, all such products in the US carry similar warnings and precautions about estrogen use, including boxed warnings about endometrial cancer, cardiovascular disease, and other risks.

The labels state that “Estrogens with and without progestins should be prescribed at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman.”

The FDA is currently reviewing the EMA PRAC recommendation, but “at this time, FDA’s determination is that the benefits of these products outweigh the risks when used according to approved labeling, even if they increase estrogen levels compared to untreated women.”

Difference in EU and US Directives: What Should the Labels Say?

Faubion said that NAMS has been working with FDA for several years to remove the boxed warning from all local vaginal estrogen therapies.

The organization has emphasized several points to support this stance, including the dramatically lower level of blood hormone levels achieved with low-dose vaginal estrogen products compared to standard systemic estrogen therapy; differences in metabolism of oral vs local vaginal products; and “the absence of randomized trial evidence or consistent observational evidence linking low-dose vaginal estrogen to cancer, cardiovascular disease, dementia, or other conditions highlighted in the boxed warning.”

Moreover, NAMS contends that the boxed warnings discourage clinicians from prescribing the products, and cause confusion by suggesting that perhaps progestins should be prescribed, when actually, “one of the benefits of low‐dose vaginal products is the lack of a need for concomitant progestins.”

The EMA spokesperson said that PRAC acknowledged that the new statement on the 4-week cap for “high-dose” estradiol products might also cause confusion among providers.

“Hence the Committee recommended that the strength of these topical products is marked clearly on the outer package as 100 microgram/g, so the comparison with alternative lower-dose products can be easily made by the prescribing physicians,” the EMA representative said.

Faubion has disclosed no relevant financial relationships.

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Generic Name: estradiol oral (ess tra DYE ole)
Brand Names: Estrace

Medically reviewed by P. Thornton, DipPharm Last updated on Mar 1, 2019.

  • Overview
  • Side Effects
  • Dosage
  • Professional
  • Interactions
  • More

What is Estrace?

Estrace tablets contains estradiol, a form of estrogen. Estradiol is a female sex hormone that regulates many processes in the body.

Estrace is used to treat menopause symptoms such as hot flashes and vaginal changes, and to prevent osteoporosis (bone loss) in menopausal women, and to replace estrogen in women with ovarian failure or other conditions that cause a lack of natural estrogen in the body.

Estrace is sometimes used as part of cancer treatment in women and men.

Estrace is also available as a vaginal cream.

Important Information

You should not use Estrace if you have: undiagnosed vaginal bleeding, liver disease, a bleeding disorder, if you will be having major surgery, or if you have ever had a heart attack, a stroke, a blood clot, or cancer of the breast, uterus/cervix, or vagina.

Do not use Estrace if you are pregnant.

Estradiol may increase your risk of developing a condition that may lead to uterine cancer. Report any unusual vaginal bleeding right away.

Using estradiol can increase your risk of blood clots, stroke, or heart attack, or cancer of the breast, uterus, or ovaries. Estradiol should not be used to prevent heart disease, stroke, or dementia.

Have regular physical exams and mammograms, and self-examine your breasts for lumps on a monthly basis while using Estrace.

Before taking this medicine

You should not use Estrace if you are allergic to estradiol, or if you have:

  • unusual vaginal bleeding that has not been checked by a doctor;

  • liver disease;

  • a history of heart attack, stroke, or blood clot;

  • an increased risk of having blood clots due to a heart problem or a hereditary blood disorder; or

  • a history of hormone-related cancer, or cancer of the breast, uterus/cervix, or vagina.

Do not use Estrace if you are pregnant. Tell your doctor right away if you become pregnant during treatment.

Using this medicine can increase your risk of blood clots, stroke, or heart attack. You are even more at risk if you have high blood pressure, diabetes, high cholesterol, if you are overweight, or if you smoke.

Estrace should not be used to prevent heart disease, stroke, or dementia, because this medicine may actually increase your risk of developing these conditions.

To make sure this medicine is safe for you, tell your doctor if you have ever had:

  • heart disease;

  • liver problems, or jaundice caused by pregnancy or taking hormones;

  • kidney disease;

  • gallbladder disease;

  • asthma;

  • epilepsy or other seizure disorder;

  • migraines;

  • lupus;

  • endometriosis or uterine fibroid tumors;

  • hereditary angioedema;

  • porphyria (a genetic enzyme disorder that causes symptoms affecting the skin or nervous system);

  • a thyroid disorder; or

  • high levels of calcium in your blood.

Using estradiol may increase your risk of cancer of the breast, uterus, or ovaries. Talk with your doctor about this risk.

Estrace lowers the hormone needed to produce breast milk and can slow breast milk production. Tell your doctor if you are breast-feeding.

How should I take Estrace?

Take Estrace exactly as it was prescribed for you. Follow all directions on your prescription label. Do not take this medicine in larger amounts or for longer than recommended.

Estradiol may increase your risk of developing a condition that may lead to uterine cancer. Call your doctor at once if you have any unusual vaginal bleeding while using this medicine.

Your doctor should check your progress on a regular basis (every 3 to 6 months) to determine whether you should continue this treatment. Self-examine your breasts for lumps on a monthly basis and have a mammogram every year while using Estrace.

If you need major surgery or will be on long-term bed rest, you may need to stop using this medicine for a short time. Any doctor or surgeon who treats you should know that you are using Estrace.

Store at room temperature away from moisture, heat, and light. Keep the bottle tightly closed when not in use.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while taking Estrace?

Avoid smoking. It can greatly increase your risk of blood clots, stroke, or heart attack while using Estrace.

Grapefruit and grapefruit juice may interact with Estrace and lead to unwanted side effects. Avoid the use of grapefruit products.

Get emergency medical help if you have signs of an allergic reaction to Estrace: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • heart attack symptoms – chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating;

  • signs of a stroke – sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance;

  • signs of a blood clot – sudden vision loss, stabbing chest pain, feeling short of breath, coughing up blood, pain or warmth in one or both legs;

  • swelling or tenderness in your stomach;

  • jaundice (yellowing of the skin or eyes);

  • memory problems, confusion, unusual behavior;

  • unusual vaginal bleeding, pelvic pain;

  • a lump in your breast; or

  • high levels of calcium in your blood – nausea, vomiting, constipation, increased thirst or urination, muscle weakness, bone pain, lack of energy.

Common Estrace side effects may include:

  • nausea, vomiting, diarrhea, stomach cramps;

  • mood changes, sleep problems (insomnia);

  • cold symptoms such as stuffy nose, sinus pain, sore throat;

  • weight gain;

  • headache, back pain;

  • breast pain;

  • thinning scalp hair; or

  • vaginal itching or discharge, changes in your menstrual periods, breakthrough bleeding.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Estrace?

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective.

Many drugs can interact with estradiol. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide. Tell your doctor about all your current medicines and any medicine you start or stop using.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Estrace only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2020 Cerner Multum, Inc. Version: 12.05.

Related questions

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Medical Disclaimer

More about Estrace (estradiol)

  • Side Effects
  • During Pregnancy or Breastfeeding
  • Dosage Information
  • Drug Images
  • Drug Interactions
  • Compare Alternatives
  • Support Group
  • Pricing & Coupons
  • En Español
  • 11 Reviews
  • Drug class: estrogens
  • FDA Alerts (2)

Consumer resources

  • Estrace (Estradiol Oral Tablets)
  • Estrace Vaginal (Advanced Reading)

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Professional resources

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Estradiol vaginal cream

If you are going to have elective surgery, you may need to stop taking this medicine beforehand. Consult your health care professional for advice prior to scheduling the surgery.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:

  • allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue

  • breast tissue changes or discharge

  • changes in vision

  • chest pain

  • confusion, trouble speaking or understanding

  • dark urine

  • general ill feeling or flu-like symptoms

  • light-colored stools

  • nausea, vomiting

  • pain, swelling, warmth in the leg

  • right upper belly pain

  • severe headaches

  • shortness of breath

  • sudden numbness or weakness of the face, arm or leg

  • trouble walking, dizziness, loss of balance or coordination

  • unusual vaginal bleeding

  • yellowing of the eyes or skin

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):

  • hair loss

  • increased hunger or thirst

  • increased urination

  • symptoms of vaginal infection like itching, irritation or unusual discharge

  • unusually weak or tired

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of the reach of children.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Protect from temperatures above 40 degrees C (104 degrees C). Do not freeze. Throw away any unused medicine after the expiration date.

NOTE: This sheet is a summary. It may not cover all possible information. If you have questions about this medicine, talk to your doctor, pharmacist, or health care provider.

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Estrogen Cream – What You Need to Know

Estrogen: the primary female sex hormone, crucial for vaginal health, good moods, restful sleep and essentially every woman’s best friend. Estrogen manages the microbiome of the vagina and keeps the skin elastic, which is especially important for sexual intercourse. But the erratic decline in estrogen levels as we go through perimenopause can lead to a wide range of symptoms including headaches, depression, increased urinary tract infections, vaginal dryness and even burning or pain during intercourse. While menopausal symptoms such as hot flashes and night sweats may require higher doses of estrogen therapy, milder symptoms may be effectively alleviated with the use of a topical estrogen cream.

Wondering if an estrogen cream might be the right option for you? Get familiar with some of the basics so you can have an informed conversation with your doctor, integrative medical practitioner or naturopath.

How Does Estrogen Cream Work?

Estrogen creams have proven effective at helping postmenopausal women reclaim their quality of life. Women naturally produce their own estrogen during their reproductive years, and the tissues lining the vagina and lower part of the urethra are very sensitive to low doses of estrogen. When an estrogen cream is applied directly, it has the ability to address vaginal atrophy (aka gradual decline) faster than hormone pills, bypassing the whole digestion process, while also minimizing any possible side effects on the rest of the body. Low-dose estrogen has been shown to be very effective against atrophy-related pain during sex, with up to 93% of women reporting significant improvement, and 57% to 75% reporting that their sexual comfort was restored.

When considering topical estrogen cream, it is important to discuss the benefits versus the risks with your health care practitioner, especially if you have had breast cancer in the past. Most forms of topical estrogen are associated with minimal side effects; however, individual responses to estrogen cream may vary. Working closely with your medical practitioner and pharmacist can help minimize side effects by ensuring the correct dose is used at all times.

Estrogen Cream Side Effects may include….

● Nausea/vomiting

● Breast tenderness

● Weight changes

In some rare cases, more significant side effects may occur and should immediately be addressed by a professional. These include changes in mental health, breast lumps, unusual vaginal bleeding, among other concerns. It is important to discuss all possible side effects with your health care practitioner before committing to a hormone treatment plan.

Why Is Bioidentical Estrogen Cream Better?

Bioidentical estrogen is superior and safer than synthetic hormones because is derived from plants and has a molecular structure that is similar to the hormones your body naturally secretes.

Ehab Mekhail, pharmacist and owner of People’s Choice Compounding Pharmacy in Richmond Hill, explains, “We use a custom dosage of natural, bioidentical estrogen in the creams and medications we make. Popular commercially available estrogen creams often use synthetic or estrogen derived from pregnant mares. However, recent research supports the use of bioidentical hormones as safer.”

Can You Buy Estrogen Cream In Canada Without A Prescription?

Short answer – no. Your hormones are not something to mess around with, which is why hormone creams are regulated by Health Canada for quality control and correct dosing. Because we are all unique and your needs aren’t the same as your neighbours’, estrogen therapy must be properly customized to each individual. It is important to have your hormonal status tested and regularly monitored as hormone levels fluctuate over time. That way you can ensure you are receiving the proper dosage. The professional guidance of your clinician eliminates any potentially harmful guesswork, while promising more successful results.

“Our goal is always to optimize your estrogen levels and bring your hormones into balance. Working closely with your doctor is fundamental to achieving that,” says Ehab Mekhail. “Our compounding pharmacists are happy to facilitate communication with your doctor to ensure you receive the very best pharmaceutical care and a custom dosage that is safe and effective at every step of your treatment.”

How Do I know If Estrogen Cream Is Right For Me?

If you suffer from vaginal dryness or irritation, or other symptoms of early menopause, begin by having your hormones tested to determine if low estrogen levels are indeed the issue. If that is the case, working in tandem with your doctor and pharmacist, a low dosage estrogen treatment can be prescribed to bring you back to your best.

Contact us to learn more about how we can help you find balance and reclaim your quality of life.

About People’s Choice Compounding Pharmacy

Serving Richmond Hill, Toronto, Markham & Vaughan

Free Ontario-Wide Shipping on all Bioidentical HRT

Located on Yonge Street, People’s Choice Pharmacy is a state-of-the-art, innovative, full-service compounding pharmacy serving Toronto, Richmond Hill, Markham and Vaughan, and shipping across Ontario. Our certified technicians with 45 years of experience will custom compound your medications using top quality, lab-tested ingredients. Call to speak to a friendly, knowledgeable Pharmacist today!

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