Estradiol is a form of estrogen, a female sex hormone that regulates many processes in the body.

It is available as an oral tablet, a topical gel or patch, vaginal cream, or as an injection.

Estradiol is used to treat menopause symptoms such as hot flashes and vaginal changes, and to prevent osteoporosis (bone loss) in menopausal women. Estradiol is also used to treat low estrogen levels in women with ovarian failure. It is also indicated to treat certain types of breast cancer and prostate cancer.

Important Information

You should not use estradiol if you have: undiagnosed vaginal bleeding, liver disease, a bleeding disorder, or if you have ever had a heart attack, a stroke, a blood clot, or cancer of the breast, uterus/cervix, or vagina.

Do not use estradiol if you are pregnant.

Estradiol may increase your risk of developing uterine cancer. Report any unusual vaginal bleeding right away.

Using this medicine can increase your risk of blood clots, stroke, or heart attack, or cancer of the breast, uterus, or ovaries. Estradiol should not be used to prevent heart disease, stroke, or dementia.

Have regular physical exams and mammograms, and self-examine your breasts for lumps on a monthly basis while using this medicine.

Before taking this medicine

You should not use this medicine if you are allergic to estradiol, or if you have:

• unusual vaginal bleeding that has not been checked by a doctor;
• liver disease;
• a history of heart attack, stroke, or blood clot;
• an increased risk of having blood clots due to a heart problem or a hereditary blood disorder; or
• a history of hormone-related cancer, or cancer of the breast, uterus/cervix, or vagina.

Do not use estradiol if you are pregnant. Tell your doctor right away if you become pregnant during treatment.

Using this medicine can increase your risk of blood clots, stroke, or heart attack. You are even more at risk if you have high blood pressure, diabetes, high cholesterol, if you are overweight, or if you smoke.

Estradiol should not be used to prevent heart disease, stroke, or dementia, because this medicine may actually increase your risk of developing these conditions.

To make sure this medicine is safe for you, tell your doctor if you have ever had:

• heart disease;
• liver problems, or prior jaundice caused by pregnancy or taking hormones;
• kidney disease;
• cancer;
• gallbladder disease;
• asthma;
• epilepsy or other seizure disorder;
• migraines;
• lupus;
• endometriosis or uterine fibroid tumors;
• hereditary angioedema;
• porphyria (a genetic enzyme disorder that causes symptoms affecting the skin or nervous system);
• a thyroid disorder; or
• high levels of calcium in your blood.

Using estradiol may increase your risk of cancer of the breast, uterus, or ovaries. Talk with your doctor about this risk.

Estradiol lowers the hormone needed to produce breast milk and can slow breast milk production. Tell your doctor if you are breast-feeding.

How it works

• Estradiol is the principal intracellular human estrogen. In women with menstrual periods, 70 to 500mcg of natural estradiol is secreted daily, depending on the phase of the menstrual cycle. After menopause, the adrenal cortex secretes a precursor to estrogen called androstenedione, which is converted by peripheral tissues into estrone, which is the most abundant circulating estrogen in postmenopausal women.
• All estrogens act by binding to estrogen receptors in estrogen-responsive tissues. Estrogens work by a negative feedback mechanism to reduce circulating levels of gonadotrophins, luteinizing hormone (LH) and follicle stimulating hormone (FSH) in postmenopausal women.
• Estradiol belongs to the class of medicines called estrogens.

How should I take estradiol?

Take estradiol exactly as it was prescribed for you. Follow all directions on your prescription label. Do not take this medicine in larger amounts or for longer than recommended.

Estradiol may increase your risk of developing uterine cancer. To help lower this risk, your doctor may also want you to take a progestin. Report any unusual vaginal bleeding to your doctor immediately.

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 a mammogram every year while using estradiol.

If you need major surgery or will be on long-term 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 this medicine.

Store at room temperature away from moisture, heat, and light. Keep the bottle tightly closed when not in use.

If you are taking injectable estrogen, dispose of any needles and syringes in an appropriate sharps container per your state laws. Do not throw away used needles into the garbage.

If you are using estradiol spray, avoid fire, flame, or smoking until the spray has dried. Do not apply lotion or sunscreen over the area for at least one hour.

Upsides

• May be used for the treatment of moderate to severe vasomotor symptoms (eg, hot flashes/flushes), and vulvar and vaginal atrophy associated with menopause. However, topical estrogen products are preferred if just prescribing for vulvar and vaginal atrophy.
• Treats low estrogen levels associated with hypogonadism, castration or primary ovarian failure.
• May be used in appropriate patients for the palliative care of breast cancer in women or men with metastatic disease.
• May be used in the palliation of advanced androgen-dependent prostate cancer.
• May be considered for the prevention of postmenopausal osteoporosis in women at significant risk and for whom non-estrogen treatments are not appropriate. However, the 2017 American College of Physicians (ACP) guidelines do not recommend its use for this indication.
• Generic estradiol is available.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Overdose can result in nausea, vomiting and vaginal bleeding.

What should I avoid while taking estradiol?

Avoid smoking. It can greatly increase your risk of blood clots, stroke, or heart attack while using this medicine.

Grapefruit and grapefruit juice may interact with estradiol and lead to unwanted side effects. Avoid the use of grapefruit products.

Estradiol side effects

Get emergency medical help if you have signs of an allergic reaction to estradiol: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• heart attack symptoms – chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating;
• signs of a stroke – sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance;
• signs of a blood clot – sudden vision loss, stabbing chest pain, feeling short of breath, coughing up blood, pain or warmth in one or both legs;
• swelling or tenderness in your stomach;
• jaundice (yellowing of the skin or eyes);
• memory problems, confusion, unusual behavior;
• unusual vaginal bleeding, pelvic pain;
• a lump in your breast; or
• nausea, vomiting, constipation, increased thirst or urination, muscle weakness, bone pain, lack of energy.

Common estradiol side effects may include:

• nausea, vomiting, diarrhea, stomach cramps;
• mood changes, sleep problems (insomnia);
• cold symptoms such as stuffy nose, sinus pain, sore throat;
• weight gain;
• headache, back pain, dizziness;
• breast pain;
• darkening of the skin or skin rash;
• thinning scalp hair; or
• vaginal itching or discharge, changes in your menstrual periods, breakthrough bleeding.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Bleeding changes, an increase in the incidence of vaginal candidiasis, breast pain and discharge, high blood pressure, nausea, vomiting, abdominal cramps, scalp hair loss, hirsutism, headache, mood disturbances, weight changes, fluid retention, skin changes, or an exacerbation of endometriosis. Estradiol may also exacerbate pre-existing conditions such as asthma, diabetes, epilepsy, and migraine and interfere with some laboratory tests.
• Estrogens are associated with an increased risk of endometrial cancer. All persistent or recurrent abnormal vaginal bleeding should be investigated, and endometrial sampling undertaken when indicated.
• An increased risk of heart attack (myocardial infarction), stroke, invasive breast cancer, pulmonary emboli and deep vein thrombosis have been associated with estrogen use (including estradiol), with or without progestins. An increased risk of dementia has also been reported in postmenopausal women 65 years of age or older.
• Estrogens, with or without progestins should be prescribed at the lowest effective dose for the shortest possible time.
• With regards to osteoporosis, estradiol has been shown to prevent vertebral bone loss in postmenopausal women. However, it does not restore bone mass to premenopausal levels and once discontinued, bone loss reverts back to the immediate postmenopausal period. The 2017 ACP guidelines for the treatment of osteoporosis do not recommend estrogen therapy for postmenopausal women with established osteoporosis.
• Should not be used in women with undiagnosed abnormal genital bleeding, with a known or suspected history of breast cancer except in appropriate patients when used for palliation, with estrogen-dependent cancer, with active deep vein thrombosis, pulmonary embolism or a history of these conditions. Estradiol is also not suitable for people with a recent history of stroke or a heart attack or other thromboembolic disease, liver disease, or known or suspected pregnancy.
• Estrogen use is associated with a two to four-fold increased risk in gallbladder disease requiring surgery. It may also lead to severe high calcium levels in patients with breast cancer or bone metastases. Visual abnormalities have also been reported.
• In women who have not had a hysterectomy, the addition or progestin for 10 days each cycle lowers the risk of endometrial hyperplasia (may be a precursor to endometrial cancer).
• Blood pressure and cholesterol/triglyceride levels should be monitored regularly throughout estrogen therapy.
• People with hypothyroidism receiving replacement therapy may require increased doses of thyroid replacement therapy when taking estrogens.

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective.

Many drugs can interact with estradiol. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide. Tell your doctor about all your current medicines and any medicine you start or stop using.

Medicines that interact with estradiol may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with estradiol. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with estradiol include:

• anastrozole
• anticoagulants, such as warfarin
• ascorbic acid
• clozapine
• corticosteroids, such as prednisone
• dantrolene
• hyaluronidase
• lamotrigine
• medications for diabetes, including insulin
• medications that induce or inhibit cytochrome p450 enzymes, CYP3A4
• NSAIDs, such as diclofenac, ibuprofen, or naproxen
• oral contraceptives
• somatropin
• theophylline
• thyroid products.

Tips

• Take estradiol exactly as directed by your doctor. The dosage varies depending on what you are taking estradiol for. Do not increase or decrease the dose unless instructed to do so. You should only take estradiol for short periods of time when used to treat menopausal symptoms. Talk to your doctor about this
• Your doctor may add a progestin to your estradiol therapy. This is to reduce the risk of changes to your endometrium.
• Report any unusual vaginal bleeding, heart pain, breast lumps, dizziness, severe headaches, shortness of breath, changes in vision, leg pains, or changes in your speech or skin to your doctor immediately.
• There is an increased risk of cancer associated with estradiol use. Discuss this with your doctor.
• Keep your scheduled appointments with your doctor. it is important you go for a checkup at least once a year. Ensure you go for your recommended screenings (eg, mammograms).
• If you smoke, have high blood pressure, diabetes, are overweight, or have high cholesterol your risk of heart disease associated with estradiol use is increased.
• Keep estradiol tablets out of reach of children. Do not share your tablets with anybody else.