Your safety is our first priority. Learn more about key medication details, possible side effects, warnings, and other important information about estradiol cream below.
Prescribing Information
Estradiol Cream is a pharmacy-compounded estrogen treatment available in multiple concentrations. Depending on the prescription, it may be applied vaginally for menopause-related vaginal dryness and discomfort or applied to the skin as part of a systemic hormone-replacement plan.
Available compounded concentrations may include 0.25 mg/g, 0.5 mg/g, 0.75 mg/g, and 1 mg/g for topical use. A separate vaginal formulation may be dispensed at 2.5 mg/mL, subject to confirmation by the dispensing pharmacy.
The prescribed concentration, application site, amount, and schedule depend on the patient’s symptoms, medical history, treatment goals, and whether local or systemic estrogen treatment is intended. Compounded estradiol cream is not an FDA-approved finished drug product, and the FDA does not review compounded drugs for safety, effectiveness, quality, or consistency before dispensing.
Black Box Warning
This compounded product does not have its own FDA-approved prescribing label. However, serious estrogen-class warnings apply.
Using estrogen without a progestogen may increase the risk of endometrial hyperplasia and endometrial cancer in patients who have a uterus. A progestogen may be prescribed with systemic estrogen to reduce this risk. Any unexplained, persistent, or recurring vaginal bleeding should be evaluated promptly.
Estrogen therapy should not be used to prevent heart disease or dementia. Estrogen treatment may increase the risk of blood clots, stroke, heart attack, breast cancer, and probable dementia. The risks vary according to the dose, route, duration, patient age, and individual medical history. Systemic absorption can also occur with vaginal estradiol cream.
Common Side Effects
Common or possible side effects may include:
- Vaginal or application-site burning, itching, redness, or irritation
- Vaginal discharge
- Spotting or abnormal vaginal bleeding
- Breast tenderness or swelling
- Headache
- Nausea, bloating, or abdominal discomfort
- Fluid retention
- Mood changes
- Skin irritation or rash
- Pelvic discomfort
- Vaginal yeast infection
- Changes in libido
Side effects and systemic absorption may vary according to the concentration, amount applied, treatment area, compounded base, and frequency of use.
Important Safety Information
Do not use Estradiol Cream if you:
- Have unexplained vaginal or genital bleeding
- Have, previously had, or are suspected of having breast cancer or another estrogen-dependent cancer
- Have an active or previous blood clot, deep-vein thrombosis, or pulmonary embolism
- Have had a stroke or heart attack
- Have a known blood-clotting disorder
- Have active liver disease or impaired liver function
- Are pregnant or may be pregnant
- Are allergic to estradiol or another ingredient in the compounded formula
These contraindications are included in FDA-approved vaginal estradiol-cream labeling.
Tell your provider about your complete medical history, including:
- Breast, uterine, ovarian, or other hormone-sensitive cancer
- Endometriosis or uterine fibroids
- Unexplained or postmenopausal bleeding
- Blood clots or a family history of clotting disorders
- Stroke, heart attack, heart disease, or high blood pressure
- High cholesterol, diabetes, obesity, or tobacco use
- Migraine headaches
- Liver, kidney, gallbladder, or thyroid disease
- Lupus
- Asthma, epilepsy, or high blood calcium
- Pregnancy, plans to become pregnant, or breastfeeding
- Upcoming surgery or an extended period of immobility
Tell your provider about all prescriptions, over-the-counter medications, supplements, and other hormone treatments you use.
Patients who have a uterus and use estradiol as systemic hormone therapy may also need a progestogen. Do not add, stop, or change progesterone without consulting your provider.
Use the lowest effective dose for the shortest appropriate duration. Your provider should periodically review whether the dose and treatment are still necessary. FDA-approved vaginal estradiol labeling recommends regularly discussing continued need for treatment with the prescribing provider.
For topical hormone-replacement use:
- Apply only to the skin area specified on the prescription label
- Do not apply to the breasts, face, broken skin, or genital area unless specifically instructed
- Wash your hands after applying
- Allow the application area to dry before dressing
- Avoid skin-to-skin transfer to another person
- Keep the treated area away from children and pets
- Follow pharmacy instructions regarding bathing, swimming, sunscreen, and application-site rotation
For vaginal use:
- Insert only the prescribed amount using the supplied applicator or click-dosing device
- Do not use more frequently than prescribed
- Wash the applicator according to the pharmacy’s instructions
- Ask the pharmacy whether the cream base may weaken latex condoms, diaphragms, or other barrier products
Contact your provider promptly if you experience new breast changes, severe headaches, worsening migraines, jaundice, significant fluid retention, or unusual vaginal bleeding.
Seek immediate medical attention for:
- Chest pain
- Sudden shortness of breath
- Coughing up blood
- Pain, warmth, redness, or swelling in one leg
- Sudden severe headache
- Sudden vision changes
- Difficulty speaking
- Facial drooping
- Weakness or numbness on one side of the body
- Facial, lip, tongue, or throat swelling
- Trouble breathing
- A severe allergic reaction
To report suspected adverse reactions, contact the FDA at 1-800-FDA-1088 or through the FDA MedWatch program.
