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Divigel

estradiol gel
Used for Menopause
Used for Menopause

Estradiol gel (Divigel) is a hormone replacement therapy used to treat symptoms of menopause, such as hot flashes and night sweats. It comes as single-use packets, and the dose is applied to the skin on your upper thigh once a day. The gel is available as both a brand-name and a generic medication. Common side effects include vaginal yeast infections, breast tenderness, and abnormal vaginal bleeding.

Reviewed by:
reviewer
Daisy Chau, PharmD
reviewer
Allison Gourley, PharmD
Last reviewed on January 6, 2025
BasicsSide effectsPros & consPharmacist tipsFAQsWarningsDosageInteractionsCostContraindicationsAlternativesLatest newsImagesReferencesPricesMedicare
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What is Estradiol gel (Divigel)?

What is Estradiol gel (Divigel) used for?

How Estradiol gel (Divigel) works

Estradiol gel (Divigel) contains man-made estradiol, a type of estrogen that the body naturally makes. During menopause, estrogen levels drop, leading to symptoms like hot flashes and night sweats. Estradiol gel (Divigel) works by replacing estrogen, which helps relieve these menopausal symptoms.

Are you looking for information on estradiol gel (EstroGel) pump or Elestrin (estradiol gel) pump instead?

Drug Facts

Common BrandsDivigel
Drug ClassEstrogen replacement
Controlled Substance ClassificationNot a controlled medication
Generic StatusNo lower-cost generic available
AvailabilityPrescription only
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What are the side effects of Estradiol gel (Divigel)?

The following side effects may get better over time as your body gets used to the medication. Let your healthcare provider know immediately if you continue to experience these symptoms or if they worsen over time.

Common Side Effects

  • Abnormal vaginal bleeding (4-10%)
  • Breast tenderness (3-9%)
  • Common cold symptoms (4-6%)
  • Upper respiratory tract infection (2-6%)
  • Vaginal yeast infection (1-6%)

Other Side Effects

  • Absence of or painful menstrual periods
  • Enlargement of breasts
  • Pounding heartbeat
  • Passing gas
  • Itchy rash
  • Tremor
  • Joint pain
  • Tiredness
  • Trouble sleeping
  • Muscle spasms
  • Weight gain

Serious Side Effects

Contact your healthcare provider immediately if you experience any of the following.
  • Heart attack: chest pain, cold sweats, left arm pain, difficulty breathing
  • Stroke: sudden weakness on one side of your body, bad headaches, trouble breathing, or changes in your speech or vision
  • Blood clot: chest pain, shortness of breath, dizziness, fast heart rate, swelling, pain, or redness in the arms or legs
  • Cancer: lumps, pain, swelling, or changes in the breasts; swollen lymph nodes, unusual or heavy vaginal bleeding, bloating, extreme tiredness, stomach-area pain

Source: DailyMed

The following side effects have also been reported

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Incidence not known

Abdominal or stomach cramps or pain

acid or sour stomach

anxiety

backache

belching

blistering, peeling, or loosening of the skin

bloating

blurred vision

breast tenderness, enlargement, pain, or discharge

change in vaginal discharge

changes in skin color

changes in vision

chest pain or discomfort

chills

clay-colored stools

clear or bloody discharge from the nipple

confusion

constipation

convulsions

cough

darkening of the urine

diarrhea

difficulty with breathing

difficulty with swallowing

dimpling of the breast skin

dizziness or lightheadedness

double vision

fainting

fast heartbeat

fever

fluid-filled skin blisters

full or bloated feeling or pressure in the stomach

headache

headache, severe and throbbing

heartburn

indigestion

inverted nipple

irregular heartbeat

itching of the vagina or genital area

joint or muscle pain

large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs

light-colored stools

loss of appetite

loss of bladder control

lump in the breast or under the arm

migraine headache

mood or mental changes

muscle cramps in the hands, arms, feet, legs, or face

muscle spasm or jerking of all extremities

nausea

noisy breathing

numbness and tingling around the mouth, fingertips, or feet

pain during sexual intercourse

pain in the ankles or knees

pain or discomfort in the arms, jaw, back, or neck

pain or feeling of pressure in the pelvis

pain, redness, or swelling in the arm, foot, or leg

painful, red lumps under the skin, mostly on the legs

pains in the stomach, side, or abdomen, possibly radiating to the back

persistent crusting or scaling of the nipple

poor insight and judgment

problems with memory or speech

puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue

rash, hives, or itching

red, irritated eyes

redness or swelling of the breast

sensitivity to the sun

skin thinness

sore on the skin of the breast that does not heal

sore throat

sores, ulcers, or white spots in the mouth or on the lips

stomach discomfort, upset, or pain

sudden loss of consciousness

sudden shortness of breath or troubled breathing

sweating

swelling

swelling of the abdominal or stomach area

thick, white vaginal discharge with no odor or with a mild odor

tightness in the chest

tremor

trouble recognizing objects

trouble thinking and planning

trouble walking

unexpected or excess milk flow from the breasts

unpleasant breath odor

unusual tiredness or weakness

unusually heavy or unexpected menstrual bleeding

vaginal bleeding or spotting

vomiting

vomiting of blood

yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

Back pain

difficulty with moving

muscle aches

muscle pain or stiffness

stuffy or runny nose

Incidence not known

Decreased interest in sexual intercourse

heavy bleeding

hives or welts

inability to have or keep an erection

increased hair growth, especially on the face

increased in sexual ability, desire, drive, or performance

increased interest in sexual intercourse

irritability

leg cramps

loss in sexual ability, desire, drive, or performance

loss of scalp hair

mental depression

mood disturbances

patchy brown or dark brown discoloration of the skin

redness of the skin

twitching, uncontrolled movements of the tongue, lips, face, arms, or legs

weight changes

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

pros-and-cons

Pros and cons of Estradiol gel (Divigel)

thumbs-up

Pros

Relieves bothersome menopausal symptoms, such as hot flashes and night sweats

Applied directly to the skin on the thighs

Only need to use once a day

Available in multiple strengths to customize your dose

thumbs-down

Cons

Raises your risk of certain cancers, blood clots, and strokes

Risk of exposing others to estrogen through skin contact

Might also need to take a progestin medication if you have a uterus

Need to wait for the gel to dry completely before bathing, showering, or swimming

pharmacist-tips

Pharmacist tips for Estradiol gel (Divigel)

pharmacist

  • Estradiol gel (Divigel) can transfer to others through skin-to-skin contact with the application site. After applying the gel, let it dry completely and wear clothing over the area. And wash your hands with soap and water immediately after applying the medication. Avoid letting others contact the application area for at least 1 hour.

    • If you miss a dose of estradiol gel (Divigel), and your next dose is less than 12 hours away, skip the missed dose and apply your regular dose the next day. If the missed dose is more than 12 hours away, apply the missed dose and continue with your regular schedule the following day.

      • Avoid swimming, showering, and bathing for at least 1 hour after applying estradiol gel (Divigel). Washing the area too soon can reduce the amount of estrogen your body absorbs, affecting how well the medication works.

        • Using sunscreen while applying estradiol gel (Divigel) might change how much estrogen your body absorbs. If you’re unsure about using sunscreen with this medication, ask your prescriber for guidance.

          • If you have a uterus, your prescriber might recommend taking a progestin medication along with estradiol gel (Divigel) to lower the risk of uterine (endometrial) cancer. Check with your prescriber to confirm your treatment plan.

            • Using estradiol gel (Divigel) for a long time can raise the risk of serious health problems, such as breast cancer and heart attacks. That's why it's important to use the lowest dose for the shortest possible duration. Talk with your prescriber regularly to decide if you should continue treatment.

              • Estradiol gel (Divigel) is flammable, meaning it can easily catch on fire. Avoid fire, flames, or smoking until the gel has dried to protect yourself and others around you.

                • Store estradiol gel (Divigel) at room temperature. Throw away used packets in the trash safely to prevent accidental contact with others.

                  How to use estradiol gel (Divigel):

                  • Make sure to read the instructions for use carefully before using the medication to make sure you apply the dose correctly.

                    • (1) Wash and dry your hands, then sit comfortably. (2) Open the estradiol packet and squeeze the entire contents onto your upper thigh. Spread it in a thin layer over an area that's 5 by 7 inches. You don't need to massage or rub in the gel. Wait for it to dry completely before putting on clothes. (3) Throw away the empty packet and wash your hands with soap and water to prevent transferring the gel to others.

                      • Alternate application between your left and right thigh each day to prevent skin irritation.

                        • If you spill any gel, don't open a new packet. Just skip that dose and apply your normal dose the next day.

                          faqs

                          Frequently asked questions about Estradiol gel (Divigel)

                          How long does estradiol gel (Divigel) take to work?
                          Estradiol gel (Divigel) usually starts to relieve menopausal symptoms, like hot flashes, within about 2 weeks. For some people, it can take months to feel the full effects. If you don’t see any improvement after a few months, talk to your prescriber.
                          Does estradiol gel (Divigel) help with weight loss?
                          Not likely. Some people have reported weight changes, including both weight gain and weight loss, while using estradiol gel (Divigel). But these changes are usually caused by hormonal shifts during menopause, not the medication itself. If you’re worried about weight changes during menopause, talk to your gynecologist.
                          Is estradiol gel (Divigel) bioidentical?
                          Yes. Estradiol gel (Divigel) is a bioidentical hormone because it contains estradiol only. Estradiol is a man-made hormone that's chemically similar to the estrogen hormone your body makes.
                          Where do you apply estradiol gel (Divigel)?
                          Apply estradiol gel (Divigel) to clean, dry skin on the upper thighs. Use it on one thigh at a time, and alternate between thighs each day. Spread the gel in a thin layer over the area, but you don't need to rub it in. Avoid applying it to broken or irritated skin, and let the gel dry before putting on clothes. Be sure to wash your hands after application to prevent spreading the medication to others.
                          Can you put estradiol gel (Divigel) on your face?
                          No. Estradiol gel (Divigel) is meant to be applied only to the skin on your upper thighs, as this area allows the medication to be absorbed properly. Applying the gel to your face or other areas might cause irritation or affect how well the medication works. Always follow the instructions provided by your prescriber.
                          Does estradiol gel (Divigel) cause hair loss?
                          Not typically. But menopause itself can cause changes in hair, including hair loss. If you experience hair loss while using this medication, talk to your prescriber.
                          How long does estradiol gel (Divigel) stay in your system?
                          It can take between 1 to 2 days for most of estradiol gel (Divigel) to leave your body. This is based on the medication's half-life. But how long it stays in your system can vary depending on factors like your age and health conditions, so it can be different for each person.
                          What's the difference between Divigel and EstroGel?
                          Divigel and EstroGel are both medications containing estradiol gel, but they differ in packaging and application areas. Divigel comes in single-use packets applied to the upper thigh, while EstroGel is available in a pump and applied to the entire arm. Both medications are available as brand-name and generic versions.
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                          warings-icon

                          What are the risks and warnings for Estradiol gel (Divigel)?

                          Estradiol gel (Divigel) can cause some serious health issues. This risk may be even higher for certain groups. If this worries you, talk to your doctor or pharmacist about other options.

                          risk-warning

                          Risk of blood clot

                          • Risk factors: People ages 50 years and older| High blood pressure | People identified as obese | High cholesterol | Diabetes | History of smoking cigarettes | Recent surgery or bedrest

                            Estrogens like estradiol gel (Divigel) can raise the risk of serious blood clots. Higher estrogen levels can raise blood proteins that promote clot formation. These clots can form anywhere in the body and might be life-threatening. Get medical attention right away if you have any signs or symptoms of a blood clot:

                            • Brain (e.g., stroke): weakness or numbness in your arms, legs, or face on one side of the body, trouble speaking, blurry vision, dizziness, loss of balance, trouble walking, or confusion

                              • Eyes (e.g., retinal thrombosis): trouble seeing, bulging eye, double vision

                                • Heart (e.g., heart attack): chest pain, sweating, nausea, or dizziness

                                  • Lungs (e.g., pulmonary embolism or PE): trouble breathing, chest pain, or cough

                                    • Legs (e.g., deep vein thrombosis or DVT): cramps, swelling, pain, or muscle tightness

                                      Your risk of blood clots is higher if you're older, smoke cigarettes, or have certain medical conditions. It's also higher if you're on bedrest after surgery. Your gynecologist might temporarily stop estradiol gel (Divigel) for 4-6 weeks before surgery. Talk with your gynecologist if you have any questions regarding your risk of blood clots.

                                      risk-warning

                                      Uterine (endometrial) cancer

                                      • Risk factors: Estrogen therapy without additional progestin | Using estrogen therapy for more than 1 year

                                        Estrogens like estradiol gel (Divigel) can thicken and change the lining of your uterus (endometrium). This can lead to uncontrolled growth, which might cause uterine (endometrial) cancer. To reduce this risk, it's generally recommended to take progestin, another hormone, along with estrogen. Progestin helps slow the growth of the uterine lining. Watch for warning signs of uterine cancer, such as vaginal bleeding that doesn’t stop or keeps coming back. Contact your prescriber right away if you notice any unusual vaginal bleeding.

                                        risk-warning

                                        Breast cancer

                                        • Risk factors: Personal or family history of breast cancer | Long-term use of estrogen and progestin together

                                          There's a higher risk of developing breast cancer when taking estrogen, such as estradiol gel (Divigel), and progestin medications together. The longer you take this combination, the higher your risk is. That's why it's best to use estradiol gel (Divigel) only for the shortest amount of time needed. Make sure to check your breasts regularly for changes and get breast scans (mammograms). Let your prescriber know if you notice any unusual changes in breast shape, size, or color.

                                          risk-warning

                                          Dementia

                                          • Risk factors: Age 65 years or older

                                            People using estrogen therapy like estradiol gel (Divigel) may have a higher risk of dementia, especially if treatment begins after age 65. Early symptoms of dementia include new forgetfulness, confusion, getting lost, or wandering. If you’re concerned about this risk, talk to your prescriber.

                                            risk-warning

                                            Gallbladder and liver problems

                                            • Risk factors: History of or current liver problems

                                              Estradiol gel (Divigel) can cause problems with your gallbladder, and some people have needed gallbladder surgery after starting this medication. If you experience stomach pain, nausea or vomiting that doesn't go away, fever, or a yellowing of the skin and eyes (jaundice), speak with your prescriber or get medical attention right away.

                                              The estrogen in estradiol gel (Divigel) is processed by the liver. So if your liver isn't working properly, you might have more side effects from this medication. If you currently have or have had any liver problems, including issues during a past pregnancy, you shouldn't use estradiol gel (Divigel).

                                              risk-warning

                                              Changes in calcium levels in the blood

                                              • Risk factors: Breast cancer | Cancer that has spread to the bones | Low parathyroid hormone levels

                                                Taking estrogens like estradiol gel (Divigel) can lead to severely high calcium levels in people with breast cancer that has spread to their bones. High calcium can cause symptoms like thirst, stomach pain, nausea, vomiting, constipation, bone pain, muscle weakness, or confusion. Tell your prescriber if you have any of these symptoms because you might have to stop taking estradiol gel (Divigel).

                                                Use estradiol gel (Divigel) carefully if you have low parathyroid hormone levels (hypoparathyroidism), which can lead to low calcium in your body. Let your prescriber know if you have signs of low calcium such as burning or tingling of your fingers, toes, or lips, muscle pain and cramps, or confusion.

                                                risk-warning

                                                Vision problems

                                                Although very rare, some people taking estrogens have experienced vision problems caused by a blood clot in the eyes. If you have sudden partial or complete vision loss, bulging eyes, double vision, or migraines, stop taking estradiol gel (Divigel) and tell your prescriber immediately.

                                                risk-warning

                                                High triglycerides

                                                • Risk factors: High levels of triglycerides

                                                  Estrogens can raise the amount of fats in your blood (triglycerides), which can lead to heart problems or pancreatitis, a serious inflammation of the pancreas. Your prescriber might recommend regular blood tests to watch for this while you're taking estradiol gel (Divigel). If you experience sudden stomach or back pain, nausea, vomiting, sudden weight loss, or a fast heart rate, contact your prescriber or seek medical care right away.

                                                  risk-warning

                                                  Low thyroid hormone levels (hypothyroidism)

                                                  • Risk factors: Low thyroid hormone levels

                                                    Estradiol gel (Divigel) can affect thyroid hormone levels in your blood. If you're taking medications for low thyroid hormone levels, you might need a higher dose of your thyroid replacement therapy. Your prescriber might recommend regular blood tests to check your thyroid hormone levels while you're taking this medication.

                                                    risk-warning

                                                    Fluid Retention

                                                    • Risk factors: History of heart or kidney problems

                                                      Estrogen products like estradiol gel (Divigel) can cause some fluid retention or edema, especially in people with heart conditions, like congestive heart failure, or kidney problems. If you notice unusual swelling in any part of your body or if you suddenly gain weight over a short period of time, let your care team know.

                                                      risk-warning

                                                      Worsening of other medical conditions

                                                      • Risk factors: History of asthma or diabetes | History of lupus | History of seizures or migraines | History endometriosis

                                                        Taking estrogen-containing medications like estradiol gel (Divigel) can worsen certain medical conditions. These include endometriosis, hereditary angioedema, asthma, diabetes, migraine, and seizures. Before you start estradiol gel (Divigel) let your healthcare team know about your past medical history so they can talk with you about the risks and benefits of taking this medication.

                                                        risk-warning

                                                        Potential skin-to-skin transfer

                                                        There's a chance that estradiol gel (Divigel) could transfer to someone else through skin-to-skin contact with the application site. To avoid this, make sure the gel is completely dry before allowing others to touch the area. Once the gel is dry, cover the application site with clothing.

                                                        dosage

                                                        Estradiol gel (Divigel) dosage forms

                                                        The average cost for 1 carton of 30 packets of 0.5mg gel of Estradiol gel (Divigel) is $177.00 with a free GoodRx coupon. This is 14.46% off the average retail price of $206.93.
                                                        carton
                                                        Carton
                                                        DosageQuantityPrice as low asPrice per unit
                                                        30 packets of 0.25mg gel1 carton$179.20$179.20
                                                        30 packets of 0.5mg gel1 carton$177.00$177.00
                                                        30 packets of 0.75mg gel1 carton$179.45$179.45
                                                        30 packets of 1mg gel1 carton$180.38$180.38
                                                        30 packets of 1.25mg gel1 carton$145.46$145.46

                                                        Typical dosing for Estradiol gel (Divigel)

                                                        The typical starting dose is 0.25 grams (one packet), applied to the skin of either your right or left upper thigh once a day. If needed, your prescriber might raise your dose up to the maximum of 1.25 grams per day.

                                                        More on Estradiol gel (Divigel) dosage forms

                                                        Health: Estradiol: menopausal woman patch on arm 1467093339

                                                        Topical Estradiol Dosages for Adults: Your GoodRx Guide

                                                        Written by Emilie White, PharmD
                                                        interactions

                                                        Interactions between Estradiol gel (Divigel) and other drugs

                                                        Estradiol gel (Divigel) may interact with certain medications or supplements. Always let your doctor and pharmacist know about any other medications or supplements (including prescribed and over-the-counter medications, vitamins, and dietary or herbal supplements) that you are currently taking. The list below does not include all possible drug interactions with Estradiol gel (Divigel). Please note that only the generic name of each medication is listed below.

                                                        Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

                                                        Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

                                                        Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

                                                        drug-cost

                                                        How much does Estradiol gel (Divigel) cost?

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                                                        contraindications-icon

                                                        Estradiol gel (Divigel) contraindications

                                                        Contraindications are specific health conditions or situations in which a person should not take a medication due to safety concerns. If you have any of the following conditions or if any of the following apply to you, let your healthcare provider know because Estradiol gel (Divigel) will not be safe for you to take.

                                                        • Undiagnosed abnormal vaginal bleeding

                                                        • History of breast cancer

                                                        • History of cancer that depends on estrogen for growth

                                                        • Blood clots or blood clotting conditions

                                                        • History of stroke or heart attack

                                                        • Liver problems

                                                        alternatives

                                                        What are alternatives to Estradiol gel (Divigel)?

                                                        There are a number of medications that your doctor can prescribe in place of Estradiol gel (Divigel). Compare a few possible alternatives below.
                                                        Estradiol gel (Divigel)
                                                        Used for:
                                                        $145.46 Lowest GoodRx priceView Prices
                                                        Evamist (estradiol)
                                                        Used for:
                                                        $81.09 Lowest GoodRx priceView Prices
                                                        Climara (estradiol patch)
                                                        Used for:
                                                        $28.46 Lowest GoodRx priceView Prices
                                                        images

                                                        Estradiol gel (Divigel) images

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                                                        References

                                                        Best studies we found

                                                        Files, J. A., et al. (2011). Bioidentical hormone therapy. Mayo Clinic Proceedings.

                                                        Furness, S., et al. (2012). Hormone therapy in postmenopausal women and risk of endometrial hyperplasia. The Cochrane Database of Systematic Reviews.

                                                        Hedrick, R. E., et al. (2009). Transdermal estradiol gel 0.1% for the treatment of vasomotor symptoms in postmenopausal women. Menopause.

                                                        View All References (2)

                                                        NorthStar Rx LLC. (2024). Estradiol gel [package insert]. DailyMed.

                                                        Rosendaal, F. R., et al. (2002). Female hormones and thrombosis.

                                                        GoodRx Health has strict sourcing policies and relies on primary sources such as medical organizations, governmental agencies, academic institutions, and peer-reviewed scientific journals. Learn more about how we ensure our content is accurate, thorough, and unbiased by reading our editorial guidelines.
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