How It Works
Estradiol gel works to counteract the natural drop in estrogen levels that occurs during menopause. By mimicking the hormone estrogen, this gel helps address menopause symptoms that are caused by a loss of estrogen.
When the gel is applied to the skin, estradiol is absorbed into the bloodstream. By introducing estradiol through the skin (transdermal delivery) rather than the digestive tract, it bypasses the initial process of liver metabolism that occurs with oral estrogen therapies. This may reduce the risk of certain complications of estrogen replacement therapy.
| Quick Facts | |
|---|---|
| Common Brands | EstroGel, Divigel, Elestrin |
| Drug Class | Estrogen replacement |
| Generic Status | Generic is available |
| Availability | Prescription only |
Dosing
Providers typically recommend patients use the lowest effective dose of estradiol gel. A common dose is one pump (1.25 grams) of estradiol gel per day.
Instructions state that estradiol gel should be applied to clean, dry skin. Pharmacists suggest dispensing the dose into the hand and spreading it thinly over the entire arm, from the wrist to the shoulder. After application, the gel should be allowed to dry completely for about five minutes without rubbing or massaging it into the skin.
Note: Dosing information below is educational only. Your prescribing physician will determine your specific dose based on your individual health needs. Always follow your healthcare provider’s instructions for exact dosing.
Uses
FDA-Approved Uses
Estradiol gel is FDA-approved to treat different symptoms and complications during and after menopause. This includes hot flashes and night sweats, as well as vaginal dryness and pain during sex. Estradiol gel is also approved to reduce bone loss and help prevent osteoporosis after menopause.
Off-Label Uses
You may see estradiol gel prescribed for uses that are not “FDA-approved.” This is a common and legal practice called “off-label” prescribing, where a doctor uses their clinical judgment to prescribe a drug for a different (but well-researched) purpose.
While estradiol gel does not have frequently prescribed off-label uses, doctors may recommend this medication for hormone-related health issues based on their medical assessment of a patient’s situation.
Side Effects
Like all medications, estradiol gel can cause side effects. Some common side effects may improve over time as your body adjusts to the medication. Other side effects may be serious and require medical attention.
Common Side Effects
- Mild skin irritation at the application site
- Breast pain or tenderness
- Headache
- Flatulence
- Nausea and vomiting
- Stomach pain, discomfort, cramps, or bloating
- Pain in the arms, legs, or back
- Fluid retention and swelling
- Flu-like symptoms
- Irregular vaginal bleeding or spotting
- Vaginal yeast infection
- Hair loss
- Skin rash and itching
- Diarrhea
- Dizziness
- Trouble sleeping
- Weight gain
Serious Side Effects
Serious side effects are rare, but it’s important to know what to look for if they do occur.
- Blood clots: Estrogen therapy can raise the risk of developing blood clots in the arteries or veins, which could potentially cause a stroke, heart attack, deep vein thrombosis (DVT), or pulmonary embolism.
- Endometrial cancer: Using transdermal estradiol can thicken the lining of the uterus, potentially increasing the risk of uterine cancer. This risk may be higher if estradiol is used without a progestin medication.
- Breast cancer: There may be a higher risk of developing breast cancer when using estradiol gel, particularly with long-term use of combined estrogen and progestin therapy.
- Ovarian cancer: Treatment with estradiol gel may result in a higher risk for cancer in the ovaries.
- Gallbladder problems: Estradiol gel may trigger gallbladder issues, including gallstones or cholecystitis.
- Memory problems: Using estrogen therapies like estradiol gel may increase the risk of developing memory problems or cognitive impairment, especially if treatment starts at age 65 or older.
- Increased blood pressure: Estradiol gel may elevate blood pressure.
- Severe allergic reactions: Estradiol gel can induce allergic responses, which may present as hives, breathing problems, or swelling of the face, lips, tongue, or throat.
- Liver injury: Because the liver processes estrogen, estradiol gel can potentially cause liver damage or exacerbate underlying liver dysfunction.
- High triglycerides: Estrogen therapy can raise levels of triglycerides in the blood, which may contribute to cardiovascular problems or pancreatitis.
- Changes in calcium levels: Estradiol gel can cause excess calcium levels in those with breast cancer that has spread to the bones. It can also negatively impact calcium regulation in patients with low parathyroid hormone levels.
- Vision problems: In rare instances, individuals taking estrogens have experienced vision loss, double vision, or bulging eyes due to blood clots in the eyes.
Call your doctor immediately if you experience any concerning or prolonged symptoms.
Pharmacist Tips
Prevent Secondary Transfer
Estradiol gel can be transferred to others through skin-to-skin contact, so standard guidelines suggest letting the area dry completely, covering it with clothing, and avoiding contact with others for at least one hour.
Wash Your Hands
Instructions for estradiol gel note that it is critical to wash your hands with soap and water immediately after applying the gel. This limits the accidental spread of the hormone to other body parts or other people.
Wait Before Bathing
Providers typically recommend applying the gel after bathing or showering. Washing the area too soon after application can reduce how much estrogen your body absorbs.
Space Out Application Of Skincare Products
Applying sunscreen too soon after the gel can reduce estrogen absorption, while applying moisturizer can increase it. Consult your doctor for guidance about applying any specific skincare product.
Consider Combining With Progestin
If you have a uterus, your doctor may recommend taking a progestin medication alongside estradiol gel to reduce the risk of endometrial cancer.
Avoid Open Flames
Estradiol gel is highly flammable, so keep the medication away from open flames and cigarettes.
Prime The Pump Before First Use
If using a pump, it must be primed by pressing down five times over a sink and then washing that gel away. The pump does not need to be primed again after this initial step.
Drug Interactions
Certain medications and substances can interact with estradiol gel, potentially altering how it works or increasing the risk of side effects.
- Grapefruit juice: Do not consume grapefruit juice while using estradiol gel, as it may increase estradiol levels in the blood and cause serious side effects.
- Alcohol: Drinking alcohol while using estradiol gel may heighten the risk of liver damage.
- St. John’s wort: This common herbal supplement that is used to treat depression may interact with estradiol gel.
- Seizure medications: Medicines used to control seizures, such as phenobarbital or carbamazepine, can alter how estradiol gel works in the body.
- Antibiotics: Certain antibiotics, including rifampin, erythromycin, and clarithromycin, can alter blood levels of estradiol.
- Antifungal medications: Medications used to treat fungal infections, such as ketoconazole or itraconazole, may affect blood levels of estradiol.
- HIV medications: Ritonavir, a medicine commonly prescribed to treat HIV, is known to interact with estradiol gel.
Always give your doctor and pharmacist a complete list of all your medications, vitamins, and supplements to check for potential interactions.
FAQs
Why must you prevent secondary skin contact between the estradiol gel application site and people or pets?
If your skin hasn’t completely dried after application, estradiol gel can unintentionally transfer from your skin to other people and pets. Standard guidelines suggest washing your hands immediately after use, allowing the gel to dry completely, and covering the site with clothing to protect those around you.
How much time must you wait after applying estradiol gel before you can safely shower, swim, or wash the application site?
Getting the area wet too soon after application can wash away estradiol gel and reduce the amount of estrogen your body absorbs. Providers typically recommend applying the gel after your daily bath or shower and waiting as long as possible before swimming or washing the area again.
Is it safe to apply sunscreen or moisturizing lotion over the skin area where estradiol gel was administered?
Adding topical products like sunscreen or moisturizer can alter estradiol absorption. Studies indicate that applying sunscreen within one hour after the gel decreases absorption, while using moisturizer within one hour increases absorption. Talk to your doctor about the safest timeline for applying skincare products when using estradiol gel.
Does estradiol gel provide localized treatment for vaginal dryness, or systemic symptom relief?
Estradiol gel provides systemic relief because it is absorbed through the skin and enters the bloodstream, raising overall estrogen levels. By modifying the body’s hormone balance, it helps relieve generalized symptoms like hot flashes while also addressing localized vaginal symptoms, such as dryness and irritation.
How does transdermal estradiol gel bypass the liver metabolism associated with oral estrogen tablets?
By delivering estradiol topically through the skin, the medication directly enters the bloodstream. This transdermal delivery mechanism intentionally avoids the liver metabolism process that occurs with oral medications. This type of absorption may help lower the risk of some complications linked to oral estrogen therapies.
Can utilizing estradiol gel cause fluid retention or bloating?
Yes, using estrogen therapies like estradiol gel can cause fluid retention, bloating, or swelling. This risk may be higher for individuals who have pre-existing kidney problems or heart conditions, such as congestive heart failure.
How should you apply estradiol gel, and is hand-washing required immediately after application?
Providers typically recommend pumping the prescribed dose into the palm of your hand and spreading it thinly over your entire arm, from the wrist up to the shoulder. They advise against massaging or rubbing the gel into your skin.
Immediate hand-washing with soap and water is strongly recommended to prevent the accidental transfer of the hormone to others.
Does estradiol gel treat or prevent postmenopausal osteoporosis to the same degree as other estrogen formulations?
Estradiol gel works similarly to other estrogen therapies by increasing systemic hormone levels, which can help preserve bone density and reduce bone loss. Estradiol gel is FDA-approved to prevent postmenopausal osteoporosis. Its effectiveness depends on the prescribed dosage and overall plan for bone health.
Why must you avoid applying estradiol gel to the breasts or the genital region?
Estradiol gel from a pump is specifically approved for topical application on the arm. Applying estradiol gel to the breasts, face, or genital areas could lead to skin irritation and may affect the way that the body absorbs the medication.
Comparable Medications
Estradiol gel, Oral estradiol, Estradiol transdermal patch (Climara), Estradiol vaginal ring (Estring), Estradiol gel (Divigel)?
Oral estradiol
Oral estradiol is an estrogen medication taken by mouth as a pill, meaning it must be metabolized by the liver before entering the bloodstream.
Estradiol Transdermal Patches
From $65.99
The estradiol transdermal patch is an adhesive patch that is worn for multiple consecutive days to provide a steady, continuous release of estrogen.
Estradiol vaginal ring
The estradiol vaginal ring is a localized hormone delivery method where the medication is inserted into the vagina via a flexible ring.
Estradiol Gel (Divigel)
While Divigel also uses topical estradiol gel, it comes in single-use packets (instead of a pump) and is applied to the upper thigh rather than the arm.
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Important: Information on this page is for educational purposes only. Prescribing decisions are made by independent, licensed providers. TelyRx operates technology-enabled pharmacies and a telehealth platform that connects patients with licensed providers. Prescriptions, when provider-approved and issued, are filled and shipped by TelyRx-affiliated pharmacies. We do not employ physicians or make prescribing decisions. Learn more about our editorial standards here.