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Key takeaways
Estradiol comes in various forms and is primarily used to treat symptoms of menopause.
Side effects vary by form and dosage but may include gastrointestinal issues, irregular vaginal bleeding, headaches, and breast tenderness, among others. They’re generally mild and may improve over time.
Not all forms of estradiol may be suitable for people with certain health conditions.
Estradiol is a generic prescription medication that is approved by the Food and Drug Administration (FDA) primarily to treat symptoms of menopause, such as hot flashes and vaginal dryness. When taking estradiol or any medication, it’s important to weigh the benefits and risks, including potential side effects.
What is estradiol?
Estradiol (E2) is the strongest of three forms of estrogen naturally produced by the female body. These also include estrone (E1) and estriol (E3), which are hormones that bind to the body’s estrogen receptors. Both estradiol and estriol can be used as hormone replacement therapy in postmenopausal women, but estradiol is far more commonly used. Estriol is only available in compounded drugs that are not approved by the Food and Drug Administration (FDA).
Estradiol is available as a tablet, transdermal patch, gel, vaginal cream, or vaginal ring. Estradiol brand names include Alora, Estrogel, Vagifem, Climara, and Estrace.
RELATED: Questions to ask your doctor about menopause
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Common side effects of estradiol
Many common side effects of estradiol improve with time. A healthcare professional will work with you to find the best form of estradiol for your particular needs. Some of the more common side effects of estradiol include:
- Vaginal spotting or breakthrough bleeding
- Breast tenderness or pain
- Stomach cramps, nausea, or bloating
- Headache
This isn’t a complete list of common side effects. Talk with your healthcare provider about any new or worsening symptoms you experience after starting estradiol.
Topical estradiol may also cause a skin reaction at the site of patch or gel application.
Vaginal cream or rings may cause irritation, itching, or yeast infections.
Serious side effects of estradiol
Though serious side effects are not common when taking estradiol, the following may occur:
- Blood clots, heart attack, and stroke
- High blood pressure
- Increased risk of cancer in the breast, ovary, and uterus
- Gallbladder disease and pancreatitis
- Severe allergic reactions
- Intestinal obstruction, vaginal ulcers, or toxic shock syndrome (when using the vaginal ring)
The risk of serious side effects is typically lower for people using local estradiol replacement in the form of vaginal creams. This isn’t a complete list of possible serious side effects. Your healthcare provider can best help you evaluate the potential risks and benefits of estradiol therapy based on your symptoms and your health conditions.
RELATED: The impact of hormones on women’s mental health
Estradiol contraindications and warnings
There are drug warnings you should be aware of when taking estradiol, and certain people should not take it.
Overdose
If an overdose is suspected, contact your local poison control center or seek emergency medical attention immediately. Taking too much medication, in the wrong way, or by a person it was not prescribed for may be dangerous. Maximum dosage is as follows for menopausal symptoms, but the actual dosage will vary based on the condition being treated:
- Oral: 2 mg per day, three weeks on and one week off
- Patch: 0.1 mg per day given in a patch that is replaced once or twice a week
- Topical gel: 1.25 grams per day
- Vaginal cream: 4 grams of .01% cream daily for 2 weeks, tapered to 1 gram one to three times a week
- Vaginal ring: One ring every 90 days
Restrictions
You should not take estradiol if you:
- Are allergic to estradiol
- Experience unusual vaginal bleeding that doesn’t have a diagnosis
- Have a history of blood clots, breast cancer, or any estrogen-dependent cancer
- Have liver disease
- Are pregnant or breastfeeding
- Have a blood condition that puts you at risk for clots
Certain patients should use caution when taking estradiol. Tell your healthcare provider if you:
- Are older than 65
- Have kidney disease
- Have heart disease, high blood pressure, elevated cholesterol, or diabetes
- Smoke tobacco
- Have endometriosis
- Experience migraine headaches or seizures
This isn’t a complete list of estradiol precautions. Talk with your healthcare provider about all your current and past health conditions, as well as your family health history.
Estradiol interactions
If you are taking a blood thinner, be sure to let your healthcare provider know, as adverse effects may occur. The following prescription drugs should be avoided when taking estradiol:
- Fezolinetant (treats hot flashes)
- Tranexamic acid (promotes blood clotting)
Many other drugs and supplements can interact with estradiol, so be sure to tell your healthcare provider about all medications you are taking, including over-the-counter and prescribed medications, vitamins, and supplements. You may need to adjust the dose of one or more medications.
If you are taking estradiol, it’s important that you do not smoke or use tobacco products. Smoking combined with estradiol can increase your risk of blood clots, stroke, high blood pressure, and heart attack.
Avoid grapefruit and products containing grapefruit because they may raise estradiol levels in the body.
Consult with your healthcare provider about drinking alcohol. Some studies have shown that alcohol increases the risk of breast cancer and other types of cancer.
How to avoid estradiol side effects
The best way to prevent estradiol side effects is to take it as prescribed and according to the drug information contained in the package insert. How often you take estradiol will depend on the form and your individual circumstances. Other ways to avoid side effects include:
- To avoid an upset stomach, take the oral form of estradiol with food or shortly after eating, and take it at the same time each day.
- If you are using the gel form of estradiol, you can apply it at any time of the day, but be sure to do so around the same time each day to minimize side effects.
- If you miss a dose and it’s more than 12 hours before your next dose, take the missed dose right away. Otherwise, skip the dose and wait until it is time to take your next one.
- Take the minimum effective dose of estradiol. Your healthcare provider will monitor your symptoms and side effects on a regular basis.
- Get regular checkups and routine screening tests as recommended by your healthcare provider.
- Tell your healthcare provider about any persistent or unusual vaginal bleeding. You may need additional tests to find out the cause. You may also be given an additional hormone called a progestin to take together with estradiol.
Estradiol is available in many forms to treat symptoms associated with menopause. Its benefits outweigh the risks for most people who take it, but it’s not right for everyone. To decrease the risks of common or serious side effects, only take estradiol as prescribed by a qualified healthcare provider.
- Estradiol topical, MedlinePlus (2025)
- Estradiol, StatPearls (2023)
- Estradiol interactions, Mayo Clinic (2025)
- Alcoholic beverage consumption and female breast cancer risk: A systematic review and meta‐analysis of prospective cohort studies, Alcohol, Clinical and Experimental Research (2024)