Brand Names:

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

Dosage Forms:

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

Uses of This Medicine:

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 This Medicine:

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.

Children—

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

Older adults—

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.

Breast-feeding—

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.

Other 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.

• Amifampridine
• Apalutamide
• Aprepitant
• Armodafinil
• Artemether
• Belzutifan
• Bexarotene
• Boceprevir
• Bosentan
• Bupropion
• Carbamazepine
• Cenobamate
• Ceritinib
• Clobazam
• Conivaptan
• Dabrafenib
• Darunavir
• Dexamethasone
• Dicloxacillin
• Donepezil
• Doxycycline
• Efavirenz
• Elagolix
• Elvitegravir
• Encorafenib
• Enzalutamide
• Eslicarbazepine Acetate
• Etravirine
• Fosaprepitant
• Fosnetupitant
• Fosphenytoin
• Griseofulvin
• Isotretinoin
• Ivosidenib
• Lesinurad
• Lixisenatide
• Lorlatinib
• Lumacaftor
• Mavacamten
• Minocycline
• Mitapivat
• Mitotane
• Mobocertinib
• Modafinil
• Mycophenolic Acid
• Nafcillin
• Netupitant
• Nevirapine
• Nirmatrelvir
• Oxcarbazepine
• Phenobarbital
• Phenylbutazone
• Phenytoin
• Pitolisant
• Pixantrone
• Prednisone
• Primidone
• Red Clover
• Rifabutin
• Rifampin
• Rifapentine
• Rufinamide
• Secobarbital
• St John's Wort
• Sugammadex
• Tazemetostat
• Telaprevir
• Theophylline
• Topiramate
• Ulipristal
• Valproic Acid

Other interactions—

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 This Medicine:

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 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 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 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 This Medicine:

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.

Side Effects of This Medicine:

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.