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Vagifem Side Effects

Generic name: estradiol topical

Medically reviewed by Last updated on Apr 22, 2024.

Note: This document contains side effect information about estradiol topical. Some dosage forms listed on this page may not apply to the brand name Vagifem.

Applies to estradiol topical: vaginal cream, vaginal insert, vaginal tablet. Other dosage forms:


  • Estrogens may raise the chance of uterine cancer. Progestins may lower this chance. A warning sign for cancer of the uterus is vaginal bleeding. Report any vaginal bleeding to the doctor.
  • Do not use estrogens to prevent heart disease or dementia. Using estrogens may raise the chances of having a heart attack, a stroke, breast cancer, ovarian cancer, a blood clot, or dementia.
  • Use estrogens with or without progestin for the shortest time needed at the lowest useful dose.

Serious side effects of Vagifem

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

Other side effects of Vagifem

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-332-1088. You may also report side effects at

For Healthcare Professionals

Applies to estradiol topical: transdermal film extended release, vaginal cream, vaginal insert, vaginal ring, vaginal tablet.


The most commonly reported side effects were headache, upper respiratory tract infection, moniliasis, genital pruritus, vulvovaginal mycotic infection, and diarrhea.[Ref]


Common (1% to 10%): Hot flushes

Frequency not reported: Deep and superficial venous thrombosis, thrombophlebitis, myocardial infarction, stroke, increase in blood pressure, congestive heart disease

Postmarketing reports: Palpitations, ventricular extrasystoles, chest discomfort, increased heart rate[Ref]


Frequency not reported: Breast cancer, endometrial cancer, ovarian cancer[Ref]


Frequency not reported: Hypersensitivity, anaphylactoid/anaphylactic reactions[Ref]


Very common (10% or more): Infection (12%)

Common (1% to 10%): Allergy

Postmarketing reports: Toxic shock syndrome (fever, nausea, vomiting, diarrhea, muscle pain, dizziness, faintness, or a sunburn-rash on face and body)[Ref]


Very common (10% or more): Endometrial disorder (15%)

Common (1% to 10%): Urinary tract infection, leukorrhea, vaginitis, vaginal discomfort/pain, vaginal hemorrhage, asymptomatic genital bacterial growth, genital moniliasis, vulvovaginal mycotic infection, vulvovaginal pruritus, bladder discomfort

Frequency not reported: Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow, breakthrough bleeding, spotting, dysmenorrhea, increase in size of uterine leiomyomata, vaginal candidiasis, change in amount of cervical secretion, changes in cervical ectropion, application site reactions of vulvovaginal discomfort including burning and irritation, genital pruritus, endometrial hyperplasia

Postmarketing reports: Ring adherence to the vaginal wall, genital edema, vulval disorder, micturition frequency, urethral disorder, endometrial hyperplasia, vaginal erosion, vaginal ulceration, ovarian cyst[Ref]


Frequency not reported: Increase or decrease in weight, reduced carbohydrate tolerance, aggravation of porphyria, hypocalcemia, increased triglycerides

Postmarketing reports: Fluid retention[Ref]


Common (1% to 10%): Abdominal pain, nausea, diarrhea, lower abdominal pain, abdominal discomfort, anorectal discomfort, dyspepsia

Frequency not reported: Vomiting, abdominal cramps, bloating, cholestatic jaundice, increased incidence of gallbladder disease, pancreatitis

Postmarketing reports: Bowel obstruction, enlarged abdomen, bloating, flatulence[Ref]


Very common (10% or more): Breast pain (10%)

Frequency not reported: Increased thyroid-binding globulin (TBG) levels, breast (tenderness, enlargement), nipple discharge, galactorrhea, fibrocystic breast changes

Postmarketing reports: Estrogen increase, gynecomastia[Ref]


Frequency not reported: Enlargement of hepatic hemangiomas[Ref]


Frequency not reported: Retinal vascular thrombosis, intolerance to contact lenses, steepening of corneal curvature

Postmarketing reports: Abnormal vision, retinal vein occlusion, blindness[Ref]


Common (1% to 10%): Flu-like symptoms, peripheral edema

Frequency not reported: Edema

Postmarketing reports: Asthenia, fatigue, feeling abnormal, malaise[Ref]


Common (1% to 10%): Insomnia

Uncommon (0.1% to 1%): Anxiety

Frequency not reported: Changes in libido, nervousness, mood disturbances, irritability

Postmarketing reports: Depression, insomnia[Ref]

Nervous system

Very common (10% or more): Headache (13%)

Frequency not reported: Migraine, dizziness, chorea, exacerbation of epilepsy, dementia

Postmarketing reports: Tremor[Ref]


Common (1% to 10%): Hyperhidrosis

Frequency not reported: Chloasma or melasma, erythema multiforme, erythema nodosum, hemorrhagic eruption, loss of scalp hair, hirsutism, pruritus, rash, urticaria, angioedema, vascular purpura

Postmarketing reports: Pruritus ani, erythematous rash, urticaria[Ref]


Common (1% to 10%): Upper respiratory tract infection, sinusitis, pharyngitis

Frequency not reported: Pulmonary embolism (venous thromboembolism or VTE), exacerbation of asthma[Ref]


Common (1% to 10%): Back pain, arthritis, arthralgia, skeletal pain

Frequency not reported: Leg cramps

Postmarketing reports: Arthropathy (including arthrosis), muscle spasms, extremity pain[Ref]


Frequency not reported: Local abrasion

Postmarketing reports: Application site rash[Ref]

Frequently asked questions


1. (2001) "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories

2. Cerner Multum, Inc. "UK Summary of Product Characteristics."

3. Cerner Multum, Inc. "Australian Product Information."

4. (2017) "Product Information. Vagifem (estradiol topical)." Novo Nordisk Pharmaceuticals Inc

5. (2017) "Product Information. Estring (estradiol topical)." Pfizer U.S. Pharmaceuticals Group

6. (2018) "Product Information. Imvexxy (estradiol topical)." TherapeuticsMD

Further information

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

Some side effects may not be reported. You may report them to the FDA.