Divigel

Pronunciation: dih-vih-jel
Generic name: estradiol gel
Dosage form: gel (0.1%)
Drug class: Estrogens

Medically reviewed by Carmen Pope, Senior Medical Editor, B. Pharm. Last updated on Sep 21, 2026.

What is Divigel?

Divigel is used after menopause to reduce moderate to severe hot flashes. When applied to the skin of the upper thigh, it is absorbed into the bloodstream. Divigel (estradiol gel) is a clear gel applied once a day.

Estradiol is a form of estrogen, a female sex hormone that regulates many processes in the body. Estrogens are produced by the ovaries until menopause (ages 45-55). Declining estrogen causes menopause symptoms like hot flashes and sweating, although some women have minimal symptoms. Surgical removal of the ovaries creates sudden "surgical menopause." 

Divigel (estradiol gel 0.1%) gained FDA approval on June 4, 2007. 

Important Information

Using estrogen-alone increases your chance of getting cancer of the uterus (womb).

• Report any unusual vaginal bleeding right away while you are using Divigel. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause.
• Do not use estrogen-alone to prevent heart disease, heart attacks, strokes, or dementia (decline of brain function)
• Using estrogen alone may increase your chances of getting strokes or blood clots.
• Using estrogen-alone may increase your chance of getting dementia, based on a study of women 65 years of age and older.
• Only one estrogen-alone product and dose has been shown to increase your chances of getting strokes, blood clots, and dementia. Only one estrogen with progestogen product and dose have been shown to increase your chances of getting heart attacks, strokes, breast cancer, blood clots, and dementia.
  • Because other products and doses have not been studied in the same way, it is not known how the use of Divigel will affect your chances of these conditions. You and your healthcare provider should talk regularly about whether you still need treatment with Divigel. 

Warnings

Do not use Divigel if you are pregnant.

Divigel can cause side effects in a child who comes into contact with the skin where you have applied Divigel.

Side effects

Common side effects

The most common side effects of Divigel are:

• Irregular vaginal bleeding or spotting
• Breast tenderness
• Vaginal yeast infection
• Upper respiratory tract (nose, sinuses, pharynx, or larynx) infection.

Serious side effects

Serious, but less common side effects of Divigel are:

• Heart attack
• Stroke
• Blood clots
• Breast cancer
• Cancer of the lining of the uterus (womb)
• Cancer of the ovary
• Dementia
• High or low blood calcium (hypercalcemia)
• Gall bladder disease
• Visual abnormalities
• High blood pressure
• High levels of fat (triglycerides) in your blood
• Liver problems
• Changes in your thyroid hormone levels
• Fluid retention
• Cancer change of endometriosis
• Enlargement of benign tumors of the uterus (“fibroids”)
• Worsening swelling of the face and tongue (angioedema)
• Changes in certain laboratory test results such as high blood sugar.

Call your healthcare provider right away if you get any of the following warning signs or any other unusual symptoms that concern you:

• new breast lumps
• unusual vaginal bleeding
• changes in vision or speech
• sudden new severe headaches
• severe pains in your chest or legs with or without shortness of breath, weakness, and fatigue
• swelling of the face, lips, and tongue with or without red, itchy bumps.

What can I do to lower my chances of a serious side effect with Divigel?

• Talk with your healthcare provider regularly about whether you should continue using Divigel.
• If you have a uterus, talk to your healthcare provider about whether the addition of a progestogen is right for you.
• See your healthcare provider right away if you get vaginal bleeding while using Divigel.
• Have a pelvic exam, breast exam, and mammogram (breast X-ray) every year unless your healthcare provider
  tells you something else.
• If members of your family have had breast cancer, or if you have ever had breast lumps or an abnormal
  mammogram, you may need to have breast exams more often.
• If you have high blood pressure, high cholesterol (fat in the blood), diabetes, are overweight, or if you use tobacco, you may have a higher chance of getting heart disease.
• Ask your healthcare provider for ways to lower your chances of getting heart disease. 

Notes:

These are not all the possible side effects of Divigel. For more information, ask your healthcare provider or pharmacist for advice about side effects. Tell your healthcare provider if you have any side effects that bother you or do not go away.

You may report side effects to the FDA at 1-800-FDA-1088 or Vertical Pharmaceuticals, LLC at 1-800-444-5164. 

Related/similar drugs

Before using this medicine

Do not start using Divigel if you:

• Have any unusual vaginal bleeding. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause
• Have been diagnosed with a bleeding disorder
• Currently have or have had certain cancers. Estrogens may increase the chances of getting certain types of cancers, including cancer of the breast or uterus (womb). If you have or have had cancer, talk with your healthcare provider about whether you should use Divigel
• Had a stroke or heart attack
• Currently have or have had blood clots
• Currently have or have had liver problems
• Are allergic to Divigel, estradiol, or any of the inactive ingredients in the gel (see the end of this guide for a list of ingredients).

Before you use Divigel, tell your healthcare provider about all your medical conditions, including if you: 

• Have any unusual vaginal bleeding

• Have other medical conditions that may become worse while you are using Divigel. Your healthcare provider may need to check you more carefully if you have certain conditions, such as asthma
  (wheezing), epilepsy (seizures), diabetes, migraines, endometriosis, lupus, angioedema (swelling of face and tongue), problems with your heart, liver, thyroid, kidneys, or high calcium levels in your blood

• Are going to have surgery or will be on bedrest. Your healthcare provider will let you know if you need to stop using Divigel

• Are pregnant or think you may be pregnant. Divigel is not for pregnant women

• Are breastfeeding. Estrogen hormones in Divigel can pass into breast milk.

How should I use Divigel?

Use Divigel exactly as prescribed by your doctor. Follow all directions on your prescription label. 

Take the dose recommended by your healthcare provider and talk to him or her about how well that dose is working for you.

• Estrogens should be used at the lowest dose possible for your treatment and only as long as needed.
• You and your healthcare provider should talk regularly (for example, every 3 to 6 months) about the dose you are using and whether you still need treatment with Divigel.

How should Divigel be applied?

Divigel should be applied 1-time a day, around the same time each day.

• Apply Divigel to clean, dry, and unbroken (without cuts or scrapes) skin. If you take a bath or shower, be sure to apply your Divigel after your skin is dry. The application site should be completely dry before dressing or swimming.
• Apply Divigel to either your left or right upper thigh. Change between your left and right upper thigh each day to help prevent skin irritation.

Your doctor should check your progress on a regular basis (every 3 to 6 months) to determine whether you should continue this treatment. Self-examine your breasts for lumps on a monthly basis, and have regular mammograms while using estradiol.

If you need surgery or medical tests or if you will be on bed rest, you may need to stop using this medicine for a short time. Any doctor or surgeon who treats you should know that you are using estradiol.

Store Divigel at room temperature away from moisture and heat.

TO APPLY:

• Step 1: Wash and dry your hands thoroughly.
• Step 2: Sit in a comfortable position.
• Step 3: Cut or tear the Divigel packet.
• Step 4: Using your thumb and pointer (index) finger, squeeze the entire contents of the Divigel packet onto the skin of the upper thigh.
• Step 5: Gently spread the gel in a thin layer on your upper thigh over an area of about 5 by 7 inches, or two palm prints. It is not necessary to massage or rub in Divigel.
• Step 6: Allow the gel to dry completely before dressing.
• Step 7: Throw away the empty Divigel packet in the trash.
• Step 8: Wash your hands with soap and water immediately after applying Divigel to remove any remaining gel and reduce the chance of transferring Divigel to other people.

Important things to remember when using Divigel

• Allow the gel to dry before dressing. Try to keep the area dry for as long as possible.
• Do not allow another person to come in contact with the area of skin where you applied the gel for at least 1 hour after you apply Divigel.
• You should not have another person apply the gel for you. However, if you need to have another person help you, have that person wear a disposable plastic glove to avoid direct contact with Divigel.
• Do not apply Divigel to your face, breast, or irritated skin.
• Never apply Divigel in or around the vagina.
• Divigel contains alcohol. Alcohol based gels are flammable. Avoid fire, flame, or smoking until the gel has dried.

What should I do if I miss a dose?

If you miss a dose, do not double the dose on the next day to catch up. If your next dose is less than 12 hours away, it is best just to wait and apply your normal dose the next day. If it is more than 12 hours until the next dose, apply the dose you missed and resume your normal dosing the next day.

Do not apply Divigel more than 1-time each day. If you accidentally spill some of the contents of a Divigel packet, do not open a new Divigel packet. Wait and apply your normal dose the next day.

What should I do if someone else is exposed to Divigel?

To reduce the chance of transfer to another person (or pet), let Divigel dry completely. Wash your hands with soap and water after application.

If someone else is exposed to Divigel by direct contact with the wet gel, have that person wash the area of contact with soap and water right away. This is especially important for men and children. The longer the gel is in contact with the skin before washing, the greater the chance that the other person (or pet) will absorb some of the estrogen hormone. This may harm them. In case of any signs or symptoms of estrogen exposure in the other person (or pet), contact your healthcare provider (or veterinarian, if appropriate).

What should I do if I get Divigel in my eyes?

If you get Divigel in your eyes, flush your eyes right away with lukewarm tap water. If you have concerns, contact your healthcare provider.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Overdose symptoms may include nausea, vomiting, stomach pain, breast tenderness, drowsiness, and vaginal bleeding.

What should I avoid while using Divigel?

Avoid getting this medicine in your eyes. If this does happen, rinse with water.

Wait at least 25 minutes after applying Divigel before you apply sunscreen to the same skin area.

Grapefruit and grapefruit juice may interact with estradiol and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

What other drugs will affect Divigel?

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines may affect how Divigel works. Divigel may also affect how your other medicines work. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get new medicine. 

Other drugs may interact with estradiol topical, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Storage

Store Divigel packets at room temperature, 68 to 77°F (20 to 25°C). 

Keep out of the reach of children. 

Ingredients

Active ingredient: estradiol

Inactive ingredients: carbomer, ethanol, propylene glycol, purified water, and triethanolamine.

Contains: 56% alcohol.

Divigel is supplied in individual foil packets, each one containing a single day's dose.

Company

Divigel is manufactured by Orion Corporation, Orion Pharma, Tengströminkatu 8, FI-20360 Turku, Finland

Divigel is manufactured for Vertical Pharmaceuticals, LLC, Alpharetta, GA 30005 USA.

Further information

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

Medical Disclaimer