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Estradiol Topical

pronounced as (es tra dye' ole)


Estradiol increases the risk that you will develop endometrial cancer (cancer of the lining of the uterus [womb]). The longer you use estradiol, the greater the risk that you will develop endometrial cancer. If you have not had a hysterectomy (surgery to remove the uterus), you should be given another medication called a progestin to take with topical estradiol. This may decrease your risk of developing endometrial cancer but may increase your risk of developing certain other health problems, including breast cancer. Before you begin using topical estradiol, tell your doctor if you have or have ever had cancer and if you have abnormal or unusual vaginal bleeding. Call your doctor immediately if you have abnormal or unusual vaginal bleeding during your treatment with topical estradiol. Your doctor will watch you closely to help ensure you do not develop endometrial cancer during or after your treatment.

In a large study, women who took estrogens (a group of medications that includes estradiol) by mouth with progestins had a higher risk of heart attacks, strokes, blood clots in the lungs or legs, breast cancer, and dementia (loss of ability to think, learn, and understand). Women who use topical estradiol alone or with progestins may also have a higher risk of developing these conditions. Tell your doctor if you smoke or use tobacco, if you have had a heart attack or a stroke and if you or anyone in your family has or has ever had blood clots or breast cancer. Also tell your doctor if you have or have ever had high blood pressure, high blood levels of cholesterol or fats, diabetes, heart disease, lupus (a condition in which the body attacks its own tissues causing damage and swelling), breast lumps, or an abnormal mammogram (x-ray of the breast used to find breast cancer).

The following symptoms can be signs of the serious health conditions listed above. Call your doctor immediately if you experience any of the following symptoms while you are using topical estradiol: sudden, severe headache; sudden, severe vomiting; speech problems; dizziness or faintness; sudden complete or partial loss of vision;double vision; weakness or numbness of an arm or a leg; crushing chest pain or chest heaviness; coughing up blood; sudden shortness of breath; breast lumps or other breast changes; discharge from nipples; difficulty thinking clearly, remembering, or learning new things; or pain, tenderness, or redness in one leg.

You can take steps to decrease the risk that you will develop a serious health problem while you are using topical estradiol. Do not use topical estradiol alone or with a progestin to prevent heart disease, heart attacks, or strokes. Use the lowest dose of topical estradiol that controls your symptoms and only use topical estradiol as long as needed. Talk to your doctor every 3-6 months to decide if you should use a lower dose of topical estradiol or should stop using the medication.

You should examine your breasts every month and have a mammogram and a breast exam performed by a doctor every year to help detect breast cancer as early as possible. Your doctor will tell you how to properly examine your breasts and whether you should have these exams more often than once a year because of your personal or family medical history.

Tell your doctor if you are having surgery or will be on bedrest. Your doctor may tell you to stop using topical estradiol 4-6 weeks before the surgery or bedrest to decrease the risk that you will develop blood clots.

Talk to your doctor regularly about the risks and benefits of using topical estradiol.

Why is this medication prescribed?

Estradiol topical gel and spray are used to treat and prevent hot flushes (hot flashes; sudden strong feelings of heat and sweating) in women who are experiencing menopause (change of life; the end of monthly menstrual periods). Estradiol topical gel is also used to treat vaginal dryness, itching, and burning in women who are experiencing menopause. However, women whose only bothersome symptoms are vaginal burning, itching, and dryness may benefit more from a medication that is applied topically to the vagina. Estradiol is in a class of medications called estrogen hormones. It works by replacing estrogen that is normally produced by the body.

How should this medicine be used?

Topical estradiol comes as a gel in single dose packets and in a pump that dispenses measured amounts of the medication to apply to the skin once a day. Topical estradiol also comes as a spray to apply to the skin as 1 to 3 sprays once a day in the morning. Estradiol gel may be applied at any time of day, but should be applied at around the same time of day every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use topical estradiol exactly as directed. Do not use more or less of it or use it more often than prescribed by your doctor.

Topical estradiol products are manufactured differently and are used in slightly different ways. Be sure that you know which topical brand you are using and how and where you should apply it. Read the manufacturer's instructions for use that came with your topical estradiol product carefully. These instructions describe how to apply topical estradiol gel or spray. Be sure that you understand these directions. Ask your healthcare provider if you have any questions about how to apply this medication.

If you are using estradiol gel in a pump, you should apply it in a thin layer to one arm, from the wrist to the shoulder. If you are using estradiol gel in single dose packets, you should apply it in a thin layer to one thigh, on the front of the thigh. If you are using estradiol, you should apply it to the inner arm. Do not apply estradiol gel or spray to your breasts or your genital area. Be sure that the skin where you will apply topical estradiol is clean and completely dry, and is not red, irritated, or broken.

If you take a bath or a shower, apply topical estradiol after you have dried your skin completely. Read the manufacturer's patient information about your topical estradiol product for information about when you can wash, shower, bathe, or swim after you apply the medication.

Estradiol gel and spray may catch fire. When you apply topical estradiol, do not smoke or go near a fire or open flame until the medication dries.

Topical estradiol is only for use on the skin. Be careful not to get topical estradiol in your eyes. If you do get topical estradiol in your eyes, wash them with plenty of warm water right away. Call a doctor if your eyes become irritated.

You should apply topical estradiol yourself. If someone else applies the medication to your skin, they should wear disposable gloves and wash their hands well with soap and water after removing the gloves.

Talk to you doctor about applying other skin preparations, including sunscreen, to skin where topical estradiol gel or spray is applied.

Estradiol topical may control your symptoms but will not cure your condition. Continue to use estradiol topical even if you feel well. Do not stop using estradiol topical without talking to your doctor. If you stop using estradiol topical, your symptoms may return.

Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

Other uses for this medicine

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

What special precautions should I follow?

Before using topical estradiol,

  • tell your doctor and pharmacist if you are allergic to estradiol gel or spray, any other estrogen products, any other medications, or any of the ingredients in estradiol gel or spray. Ask your pharmacist for a list of the ingredients in estradiol gel or spray or if you are not sure if a medication you are allergic to contains estrogen.
  • tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, and nutritional supplements, you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • The following nonprescription or herbal products may interact with topical estradiol: St. John's wort. Be sure to let your doctor and pharmacist know that you are taking these medications before you start using topical estradiol. Do not start any of these medications while using topical estradiol without discussing with your healthcare provider.
  • tell your doctor if you have or have ever had asthma; seizures; migraine headaches; a bleeding disorder; endometriosis (a condition in which the type of tissue that lines the uterus [womb] grows in other areas of the body); uterine fibroids (growths in the uterus that are not cancer); yellowing of the skin or eyes, especially during pregnancy or while you were using an estrogen product; very high or very low levels of calcium in your blood; hypoparathyroidism (condition in which the body does not produce enough parathyroid hormone [PTH; a natural substance needed to control the amount of calcium in the blood]); porphyria (condition in which abnormal substances build up in the blood and cause problems with the skin or nervous system) hereditary angioedema (inherited condition that causes episodes of swelling in the hands, feet, face, airway, or intestines); or gallbladder, thyroid, liver, pancreas, or kidney problems.
  • tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while using topical estradiol, call your doctor.
  • you should know that topical estradiol may harm other people or pets who touch the medication that is on your skin or in the container. It is most harmful to men and children. Do not let anyone else touch the skin where you applied topical estradiol for at least one hour after you apply the medication. Cover the area where you applied the medication with clothing to prevent others from coming into direct contact with the area. If someone does touch topical estradiol, that person should wash his or her skin with soap and water as soon as possible.

What special dietary instructions should I follow?

Talk to your doctor about eating grapefruit and drinking grapefruit juice while taking this medicine.

What should I do if I forget a dose?

If you forget to apply a dose of estradiol gel but remember more than 12 hours before you are scheduled to apply your next dose, apply the missed dose right away. If you remember less than 12 hours before you are scheduled to apply your next dose, skip the missed dose and continue your regular dosing schedule the next day. Do not apply extra gel to make up for a missed dose.

If you forget to apply estradiol spray in the morning, apply it as soon as you remember. Do not apply extra spray to make up for a missed dose and do not apply estradiol spray more than once each day.

What side effects can this medication cause?

Topical estradiol may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

  • headache
  • breast pain or tenderness
  • nausea
  • vomiting
  • gas
  • stomach cramps
  • weight gain
  • mood changes
  • depression
  • anxiety or irritability
  • fatigue
  • difficulty falling asleep or staying asleep
  • back or joint pain
  • runny nose
  • cough
  • flu-like symptoms
  • hair loss
  • darkening of the skin on the face
  • irritation or redness of the skin where you applied topical estradiol
  • swelling, redness, burning, irritation, or itching of the vagina
  • vaginal discharge

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately:

  • loss of appetite, fever, nausea, vomiting, tiredness, itching, dark urine, pale or light colored stools, yellowing of the skin or eyes, or pain in the upper right part of the stomach
  • itching
  • hives
  • rash or blisters on the skin
  • swelling, of the eyes, face, lips, tongue, throat, hands, feet, ankles, or lower legs
  • hoarseness
  • wheezing
  • difficulty breathing or swallowing

Topical estradiol may increase your risk of developing cancer of the ovaries and gallbladder disease that may need to be treated with surgery. Talk to your doctor about the risks of using this medication.

Topical estradiol may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online ( or by phone (1-800-332-1088).

What should I know about storage and disposal of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Do not freeze topical estradiol. Keep estradiol gel away from open flame. Dispose of your estradiol gel pump after you have used 64 doses even if it is not completely empty.

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website ( for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach.

In case of emergency/overdose

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

Symptoms of overdose may include:

  • nausea
  • vomiting
  • breast tenderness or pain
  • stomach pain
  • drowsiness and fatigue
  • vaginal bleeding

What other information should I know?

Keep all appointments with your doctor and the laboratory. Your doctor may order certain lab tests to check your body's response to topical estradiol.

Before having any laboratory test, tell your doctor and the laboratory personnel that you are using topical estradiol.

Do not let anyone else use your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Brand names

  • Divigel®
  • Elestrin®
  • Estrasorb®
  • EstroGel®
  • Evamist®

Other names

  • Estrogen Replacement Therapy
  • ERT

This branded product is no longer on the market. Generic alternatives may be available.

Last Revised - 07/15/2023