Estradiol (Vaginal)

Estradiol, brand name ESTRACE, is a vaginal drug which comprises an estrogen hormone and is used to treat unusual changes occurring in and around the vagina arising either from menopause or low estrogen levels.


Estradiol vaginal ring and tablet are used in the treatment of unpleasant changes occurring in and around the vagina, including itching, vaginal dryness, and burning. The drug is also used to treat mild to severe hot flashes, including other symptoms of low amounts of estrogen and menopause. A hormone from the vaginal ring is absorbed through a patient's vagina, which is crucial in preventing symptoms such as disturbing warm feelings in the neck, face, and chest area and subsequent sweating in women during menopause. This medication is available only with a doctor's prescription and comes in the following dosage forms'cream, tablet, and insert extended release.

Conditions Treated?

  • Vaginal dryness
  • Vaginal burning
  • Vaginal itching

Type Of Medicine?

  • Endocrine-Metabolic Agent

Side Effects

  • For the consumer

These side effects mostly occur in patients who use different estradiol products such as vaginal cream, vaginal tablet, and vaginal insert extended release.

Along with its much-needed effects, this drug may produce some disturbing side effects in patients. Although not all of these symptoms may occur, it's vital for a patient to seek medical care right away if they experience any of the following symptoms.

Less common

  • Vaginal yeast infection

Incidence not known

  • Shortage or decrease in the amount of urine
  • Change in vaginal discharge
  • Dimpling of the breast skin
  • Clear or bloody discharge from the nipple
  • Fever
  • Fast heartbeat
  • Hoarseness
  • Hives, itching, or rash
  • Inverted nipple
  • Irritation
  • Lump in the breast or under the arm
  • Joint pain, stiffness, or swelling
  • Noisy, rattling breathing
  • Redness of the skin
  • Pain, redness, or swelling in the arm or leg
  • Pain or feeling of pressure in the pelvis
  • Persistent crusting or scaling of the nipple
  • Redness or swelling of the breast
  • Redness of the skin
  • Swelling of the face, eyelids, lips, fingers, hands, feet, or lower legs
  • Sore on the skin of the breast that doesn't heal
  • Tightness in the chest
  • Troubled breathing or swallowing
  • Troubled breathing at rest
  • Vaginal bleeding

Patients should also check with their doctor if they experience any of the below symptoms of overdose:

  • Dizziness
  • Drowsiness
  • Abdominal or stomach pain
  • Tenderness of the breasts
  • Nausea or vomiting
  • Unusual tiredness or weakness

Some side effects may occur in patients that don't need any medical check-up. These side effects usually clear on their own during treatment as the patient's body adjusts to the drug. Also, the healthcare provider may tell his or her patients about ways to stop or reduce some of these side effects. Nevertheless, it's important for patients to check with their healthcare professional if any of the following side effects continue or become bothersome or if they've questions about the symptoms.

More common

  • Headache
  • Back pain
  • Thick, white vaginal discharge with mild or no odor
  • Itching or pain of the vagina or genital area
  • Weight gain

Less common

  • Chills
  • Cough
  • Body aches or pain
  • Diarrhea
  • Ear congestion
  • Sore throat
  • Sneezing
  • Nasal congestion
  • Runny nose
  • Loss of voice

Incidence not known

  • Feeling sad or empty
  • Headache--severe and throbbing
  • Lack of appetite
  • Irritability
  • Tiredness
  • Trouble sleeping
  • Trouble concentrating
  • Welts

Other side effects may also occur in some patients which are not on this list. If a patient experiences other side effects besides the ones listed above, she should check with her healthcare provider right away. The patient may also call her doctor for medical advice about side effects, or she may report such side effects to the FDA at 1-800-FDA-1088.

B) For healthcare professionals

These side effects usually occur in patients who use a variety of estradiol products such as compounding powder, oral tablet, intramuscular solution, and transdermal emulsion. This also includes transdermal gel, transdermal film extended release, transdermal spray, and vaginal ring.


  • Very common (10% or more): Breast pain (29%)
  • Common (1% to 10%): Leukorrhea, vulvovaginal pruritus, vaginal hemorrhage, vaginal discomfort, vaginal discharge, menopause symptoms, dysmenorrhea, breakthrough bleeding or spotting, breast swelling, metrorrhagia, menorrhagia, and endometrial hyperplasia
  • Uncommon (0.1% to 1%): Urinary problems
  • Rare (less than 0.1%): Galactorrhea
  • Postmarketing reports: Vaginal pain, vaginal irritation, genital pruritus, pelvic pain, changes in bleeding pattern, breast tenderness, uterine fibroids, and vaginal ulceration


  • Very common (10% or more): Arthralgia (11%) and backpain (11%)
  • Common (1% to 10%): Leg cramps


  • Very common (10% or more): Stomach pain (16%)
  • Common (1% to 10%): Nausea, flatulence, diarrhea
  • Uncommon (0.1% to 1%): Vomiting
  • Postmarketing reports: Abdominal distension


  • Common (1% to 10%): Cardiac symptoms (e.g. palpitations) and varicose veins
  • Uncommon (0.1% to 1%): Hypertension, hot flush, venous thromboembolic disease
  • Rare (less than 0.1%): Arterial hypertension
  • Postmarketing reports: Changes in blood pressure and deep vein thrombosis


Nervous system

  • Very common (10% or more): Headache (18%)
  • Uncommon (0.1% to 1%): Migraine and vertigo
  • Rare (less than 0.1%): Aggravation of epilepsy
  • Postmarketing reports: Paresthesia, migraine aggravated, and dizziness


  • Very common (10% or more): Pain (11%)
  • Common (1% to 10%): Edema
  • Uncommon (0.1% to 1%): Asthenia and weight increased
  • Postmarketing reports: Blood estrogen increase, drug ineffectiveness, exacerbation of hereditary angioedema, and fatigue


  • Common (1% to 10%): Pruritus
  • Uncommon (0.1% to 1%): Rash
  • Rare (less than 0.1%): Acne and skin discoloration
  • Postmarketing reports: Alopecia, erythematous or pruritic rash, urticaria, night sweats, contact dermatitis, hyperhidrosis, and eczema


  • Common (1% to 10%): Depression
  • Uncommon (0.1% to 1%): Mood swings, sleep disorders, and nervousness
  • Rare (less than 0.1%): Change in libido
  • Postmarketing reports: Insomnia, vaginismus, irritability, and anxiety


  • Rare (less than 0.1%): Glucose intolerance
  • Postmarketing reports: Fluid retention


  • Uncommon (0.1% to 1%): Vision abnormal NOS
  • Postmarketing reports: Contact lens intolerance and Visual disturbances


  • Rare (less than 0.1%): Liver function tests abnormalities
  • Postmarketing reports: Cholestatic jaundice


  • Very common (10% or more): Upper respiratory tract infection (17%)
  • Common (1% to 10%): Pharyngitis, vulvovaginal mycotic infection, sinusitis, rhinitis, and moniliasis genital
  • Uncommon (0.1% to 1%): Vaginitis and vaginal candidosis


  • Rare (less than 0.1%): Anaphylactic reaction (with a past history of allergic reaction)
  • Postmarketing reports: Hypersensitivity and anaphylactic reactions


  • Common (1% to 10%): Skin irritation (topical gel)
  • Postmarketing reports: Application site reaction


The dose of this treatment is usually different from person to person. Therefore, patients should follow their doctor's orders or the directions on the label at all times. Below are some average doses of this medicine frequently prescribed to patients. If a patient's dose is different from the ones provided, they should not change it unless their doctor allows them to do so.

Moreover, the amount of drug a person takes depends on the strength of the medication. Also, the number of doses taken every day, the time allowed between doses, and the length of time a patient should take their medicine, very much depend on the health problem being treated.

A) For vaginal dosage form (ring):

For hot flashes, atrophic vaginitis, and other side effects triggered by menopause

  • Adults'A single vaginal ring is usually placed into the vagina for about 3 months. The doctor may also change the dose as usual.
  • Children'Use isn't recommended.

B) For vaginal dosage form (tablet):

For treatment of atrophic vaginitis due to menopause

  • Adults--One tablet (10 micrograms) placed into the vagina once daily for about 14 days followed by another single tablet twice a week.
  • Children--Use isn't recommended.

NOTE: If a patient misses a dose of this drug, they should take it as soon as possible. However, if it's almost time for their next dose, a patient should skip the missed dose and go back to their usual dosing schedule. Be sure not to double dose.


Although certain drugs shouldn't be taken together at all, sometimes the doctor may choose to use two different medicines together even if the patient may experience an interaction. Consequently, the doctor may likely change the patient's dose or give other precautions he or she deems important. Patients taking this drug should tell their healthcare provider if they usually take any of the below medications. The following interactions are chosen on the basis of their potential significance and aren't necessarily all-inclusive.

Nevertheless, using this drug with any of the following medications isn't allowed. The doctor may decide not to treat his or her patients with this medicine or change some of the other drugs they take.

  • Tranexamic Acid

Using this drug with any of the following medications is also not recommended, but may be allowed on some occasions. If both drugs are prescribed together, the healthcare professional may change the dose or how often his or her patient take or use one or both of the drugs.

  • Crizotinib
  • Dabrafenib
  • Eslicarbazepine Acetate
  • Fentanyl
  • Isotretinoin
  • Piperaquine
  • Primidone
  • Pixantrone
  • Tizanidine
  • Theophylline

And finally, using this drug with any of the below medications may cause a high risk of certain side effects, although using both medicines may be the best treatment for patients. If both drugs are prescribed together, the healthcare provider may change the dose or how often his or her patients use one or both drugs.

  • Amprenavir
  • Alprazolam
  • Atazanavir
  • Aprepitant
  • Bosentan
  • Betamethasone
  • Bacampicillin
  • Bexarotene
  • Colesevelam
  • Carbamazepine
  • Clarithromycin
  • Cyclosporine
  • Darunavir
  • Delavirdine
  • Etravirine
  • Efavirenz
  • Fosamprenavir
  • Fosaprepitant
  • Fosphenytoin
  • Ginseng
  • Griseofulvin
  • Itraconazole
  • Ketoconazole
  • Lamotrigine
  • Levothyroxine
  • Licorice
  • Modafinil
  • Mycophenolate Mofetil
  • Mycophenolic Acid
  • Nelfinavir
  • Nevirapine
  • Oxcarbazepine
  • Phenobarbital
  • Phenytoin
  • Pioglitazone
  • Prednisolone
  • Primidone
  • Rifabutin
  • Rifampin
  • Rifapentine
  • Ritonavir
  • Rosuvastatin
  • Rufinamide
  • Selegiline
  • St John's Wort
  • Tacrine
  • Telaprevir
  • Tipranavir
  • Topiramate
  • Troglitazone
  • Troleandomycin
  • Voriconazole
  • Warfarin

Other Interactions

Some medications shouldn't be used at or around the time of eating food or eating certain types of food because interactions may likely occur. Mixing tobacco or alcohol with certain drugs may also cause interactions to occur in patients. The below interactions were chosen on the basis of their potential significance and aren't necessarily all-inclusive.

Also using this drug with any of following may cause a high risk of certain side effects but patients may avoid them to some extent. If used together, the healthcare provider may change the dose or how often his or her patients use this particular drug. The healthcare professional may also give his or her patient other instructions about the use of certain foods, tobacco, or alcohol.

  • Caffeine

Other medical issues

The occurrence of other health complications may affect the use of this particular drug. It's important for patients to tell their healthcare provider if they have any of the following medical problems:

  • Unusual or abnormal vaginal bleeding
  • Blood clots (pulmonary embolism, deep vein thrombosis)
  • Breast cancer--known or suspected
  • Heart attack
  • Liver disease
  • Protein S, protein C, or other common blood clotting disorders
  • Stroke
  • Tumors (estrogen-dependent)--known or suspected--Shouldn't be used in patients with such conditions
  • Anaphylaxis or angioedema--Patients with these conditions shouldn't use this drug
  • Asthma
  • Diabetes
  • Edema (body swelling or fluid retention)
  • Epilepsy
  • Endometriosis
  • Gallbladder disease
  • Hypocalcemia (low calcium in the blood)
  • Hypercalcemia (high calcium in the blood)
  • Hereditary angioedema (swelling of the throat, lips, face, or tongue)
  • Hypothyroidism (an underactive thyroid)
  • Hypertriglyceridemia
  • Jaundice during pregnancy or from using hormonal therapy in the past
  • Migraine headache
  • Liver tumors
  • Porphyria
  • Hypertension (high blood pressure)
  • Heart disease
  • Hypercholesterolemia (high cholesterol or fats in the blood)
  • Systemic lupus erythematosus (SLE)--Patients should use with caution, or else they risk making these conditions even worse
  • Obesity
  • Prolonged periods of immobilization--Patients should use with caution, or else they risk experiencing more severe side effects.


1. Systemic absorption may occur in some patients after using ESTRACE, and other severe reactions linked to oral estrogen treatment may also pose a threat to patients.

2. Cardiovascular disorders - Estrogen and progestin therapy usually have an increased risk of cardiovascular disorders in patients'stroke, myocardial infarction, pulmonary embolism, and venous thrombosis. If any of these side effects occur, patients should discontinue this medication.

3. Arterial vascular disorders - Risk factors for arterial vascular disease'diabetes mellitus, hypertension, tobacco use, hypercholesterolemia, and obesity may occur in some patients from the drug. Patients with a personal or family history of VTE (Venous Thromboembolism), systemic lupus erythematosus, and obesity should be carefully monitored as they're at a higher risk of getting these disorders than others.

Top researchers of a Women's Health Initiative (WHI) group found a significant amount of VTE in patients who frequently use ESTRACE. Another study of WHI found that a 2-fold greater rate of ESTRACE users being prone to VTE, including pulmonary embolism and venous thrombosis. The risk grew even worse in patients who continued using this drug for a long period than usual. If possible, patients bearing this side effect should discontinue this drug for at least 4-6 weeks before surgery, particularly that associated with a high risk of thromboembolism or long periods of intensive immobilization.

4. Episodes of frequent blood clots, strokes, or heart attacks - Some of these risks may continue even after a patient stops using this medicine. These side effects may even get much worse if a patient currently suffers from or has a high cholesterol in the blood, high blood pressure, diabetes, or if they're overweight or are cigarette smokers.

A Women's Health Initiative (WHI) study suggests that a significant number of myocardial infarctions and strokes are frequently found in women receiving ESTRACE. Another study of WHI shows that an increased risk of coronary heart disease (CHD) is frequent in patients receiving this same medication. This side effect is usually followed by a subsequent stroke, and hence patients should withdraw from using this drug.

All the same, patients should also check with their healthcare provider right away if they experience pain in the chest, difficulty speaking, confusion, double vision, headaches, and body fatigue.

5. Breast cancer - The use of progestins and estrogens in postmenopausal women usually increases the risk of breast cancer among women. Researchers have also found a smaller increased risk for estrogen-alone therapy after using this medicine for some years. Therefore, it's essential for women taking this drug to have yearly mammogram examinations to minimize the risk of getting breast cancer.

6. Dementia - Using this drug may increase the risk of a patient getting dementia, especially in women about 65 years of age and older.

7. Gallbladder disease - Among patients who use this medication, many of them are likely to experience a gallbladder disease. Postmenopausal women receiving estrogens are commonly scheduled for surgery.

8. Hypercalcemia - This drug administration may cause severe hypercalcemia in some patients, particularly those with bone metastases and breast cancer. If hypercalcemia occurs, patients should withdraw using the drug and appropriate measures taken to minimize the serum calcium level.

9. Visual abnormalities - Episodes of retinal vascular thrombosis may occur in patients receiving estrogen treatment. Patients should withdraw using this drug if they experience a sudden partial or complete loss of vision, or a sudden onset of diplopia, proptosis, or a migraine. Moreover, if examination reveals signs of retinal vascular lesions or papilledema, a patient should permanently discontinue using this medication.

10. It's very unlikely that a postmenopausal woman may become pregnant. However, it's also important for patients to know taking this medicine while pregnant could harm their unborn baby. Therefore, patients who think they have become pregnant while using this drug should tell their healthcare provider right away.

11. Using this drug over a prolonged period may increase the risk of a patient getting endometrial cancer or uterine cancer. The use of estrogens in women with intact uteri for a long period puts patients at a high risk of getting endometrial cancer. In fact, a report shows that endometrial cancer risk is about 2 to 12-fold greater among unopposed estrogen users than in non-users and appears dependent on duration of treatment and dose given to a patient.

Nevertheless, most studies show no significant increased risk linked to the use of estrogens for less than a year. The greatest risk appears in patients who have used the drug for about 5 to 10 years or more. Also, this risk seems to grow more persistent for at least 8 to 15 years after the withdrawal of estrogen therapy.

It's important for patients to talk with their doctor about this risk so that adequate diagnostic measures, including endometrial sampling, can take place to eliminate malignant tumors in patients.

Also, if a patient has a uterus (womb), she should ask the healthcare provider whether she should use a progestin drug. A patient should also check with their healthcare professional immediately if they experience abnormal vaginal bleeding from the drug.

12. Patients should tell the doctor about any unusual changes in their vagina, such as a funny shaped or narrow vagina. They should also tell their doctor if they've problems with their reproductive organs, rectum, bladder, or pelvic area.

13. Patients should tell the doctor that they're using this particular drug before undergoing any kind of surgery or emergency treatment. Sometimes this medicine may affect the results of certain medical tests, so the healthcare provider should decide whether or not a person should continue using the drug.

14. A patient should not take other medications unless they've first discussed it with their doctor. And this includes any prescription or non-prescription drugs, herbal, or vitamin supplements.


  • Store this drug in a closed container at room temperature away from moisture, heat, and direct light.
  • Keep out of the reach of children and pets.
  • Don't keep outdated medications or those no longer needed.
  • Ask the healthcare specialist on ways of properly disposing of unwanted drugs.
  • Fold the used vaginal ring in a small piece of tissue and ditch it in a trash can.
  • Be sure not to flush the vaginal ring down the toilet.


Estradiol is a vaginal medication with a hormone that's used to treat disturbing changes that may occur in and around the vagina, which occurs due to menopause or low estrogen levels in women. Each gram of ESTRACEĀ® (estradiol vaginal cream) contains 0.1 mg estradiol in a nonliquefying base packed with propylene glycol, purified water, stearyl alcohol, and sodium lauryl sulfate among other essential ingredients. This medicine has an empirical formula of C18H24O2 and molecular weight of 272.37.

Before using this medicine, the patient should tell their pharmacist or doctor whether or not they are allergic to the drug or have any other allergies. This particular product may have inactive ingredients, which may likely bring about allergic reactions or other side effects in women using the drug. Patients should also tell the pharmacist or healthcare provider about their medical history, especially of certain cancers, vaginal bleeding of unknown cause, liver disease, kidney disease, or any heart disease.

Patients with a medical history of high blood pressure, blood clot disorders, diabetes, and high cholesterol levels should also inform their doctor or pharmacist about it as well. All the same, this medicine should be taken as directed by the healthcare provider at all times. Although no serious side effects have been reported following acute ingestion of large doses of the drug, some patients may experience nausea and vomiting, and withdrawal bleeding may occur in women.