Warnings

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Medically Reviewed by Dr. Harshi Dhingra, M.D.

Last Reviewed: Oct 12, 2023

Warnings

Estradiol Risks, Warnings, and Complications

Estradiol can cause or worsen health problems in some people. Talk to your doctor about other treatment options if you are at an increased risk of complications from this medicine. Some of the risks of estradiol use include:

CARDIOVASCULAR RISK: Estradiol alone or combined estrogen/progestin therapy is associated with an increased risk of cardiovascular events such as heart attacks. Before starting estradiol, tell your doctor if you have risk factors for cardiovascular disease, such as obesity, high blood pressure, diabetes, high cholesterol, or smoking. Call your doctor immediately or seek emergency medical attention if you develop heart attack symptoms (stabbing chest pain or chest tightness, difficulty breathing, nausea, dizziness, sweating, fast heartbeat).
BLOOD CLOTS AND STROKE: Estradiol alone or in combination with progestin increases the risk of blood clots in the lungs (pulmonary embolism) and legs (deep vein thrombosis) and stroke in postmenopausal women. Long periods of immobility can increase this risk. Your provider may tell you to stop taking estradiol for 4-6 weeks before surgery. Seek emergency medical care if you develop signs of a blood clot in the legs (pain in one or both legs, cramps, swelling, or tightness) or lungs (chest pain, trouble breathing, cough). Also, seek emergency medical attention if you have signs of a stroke, such as numbness, weakness, slurred speech, blurred vision, dizziness, headache, trouble walking, loss of balance, or confusion.
ENDOMETRIAL CANCER: Taking estradiol can increase your risk of developing endometrial cancer (cancer of the uterine lining) by 2- to 12-fold, depending on the dose and the duration of use. If you still have your uterus, your healthcare provider may prescribe progestin hormone along with estradiol to lower this risk. Tell your doctor without delay if you develop abnormal or unusual vaginal bleeding that is persistent (doesn’t go away) or recurrent (keeps coming back).
BREAST CANCER: Estradiol alone or in combination with progestin increases the risk of developing breast carcinoma. The risk is higher with a longer duration of use. However, estradiol is also used for palliative treatment of breast tumors in certain cases. Your healthcare provider will prescribe the lowest dose for the shortest treatment period to lower your risk of breast carcinoma. They may ask you to do monthly self-breast exams to aid in the early detection of breast tumors. Before starting treatment, tell your provider if you have a personal or family history of breast cancers. Tell your doctor right away if you develop any changes in your breasts, such as lumps, pain, or swelling.
DEMENTIA: Studies have shown that the use of estrogen hormone therapy in women over the age of 65 years increases the risk of developing dementia. It is unclear whether dementia risk increases in younger postmenopausal women.
GALLBLADDER DISEASE AND LIVER PROBLEMS: Postmenopausal women receiving estradiol or other estrogens are at a 2- to 4-times higher risk of needing gallbladder surgery. This medication can also increase your risk of liver injury. Tell your doctor if you have a history of liver or gallbladder problems. Call your doctor immediately if you develop symptoms such as right upper stomach pain, fatigue, nausea, vomiting, loss of appetite, pain spreading to the back or shoulder, light-colored stools, dark urine, or yellowing of the skin or eyes (jaundice).
CHANGES IN CALCIUM LEVELS: Estradiol can cause severely high blood calcium levels in people with breast cancer and bone metastases (spread of cancer to the bones). Tell your doctor right away if you have symptoms such as increased thirst, confusion, stomach pain, nausea, vomiting, constipation, muscle weakness, or bone pain. You might need to stop taking estradiol. If you have low calcium levels, you should take estradiol with caution. Tell your doctor if you experience symptoms of low calcium, such as tingling or burning in the lips, fingers, or toes, muscle cramps, muscle pain, or confusion.
VISUAL ABNORMALITIES: Taking estradiol can lead to retinal vascular thrombosis (a blood clot in the eye). Stop taking estradiol and call your doctor or seek immediate medical attention if you develop vision problems in one or both eyes, double vision, bulging eyes, or migraine headaches.

Precautions Before Starting Estradiol

Tell your doctor if you have had an allergic reaction to estradiol, any of the active or inactive ingredients in estradiol formulations, other estrogen preparations, or any other medications. Your pharmacy can give you a list of ingredients.

Give your doctor or pharmacist a complete list of your medications, including prescription drugs, nonprescription drugs, vitamins, supplements, and herbal products such as St. John’s Wort. This can help avoid possible interactions between estradiol and your other medicines.

Give your doctor a complete medical history. Estradiol may not be right for people with certain medical conditions, such as personal or family medical history or breast, endometrial, or ovarian cancer, asthma, migraines, epilepsy or other seizure disorder, a bleeding disorder, uterine fibroid tumors, endometriosis, jaundice during pregnancy while using estrogen, hypoparathyroidism (low parathyroid hormone levels), high or low calcium levels, a genetic enzyme disorder called porphyria, a hereditary blood disorder such as hereditary angioedema, liver disease, gallbladder disease, kidney disease, thyroid disorder, or pancreas problems.

Talk to your doctor about eating grapefruit or drinking grapefruit juice while on this medicine.

Tell your doctor if you are pregnant, could be pregnant, are planning a pregnancy, or are breast feeding. Estrogens can slow breast milk production in lactating women.

Precautions During Use of Estradiol

Keep all your medical and lab appointments while on estradiol. Tell your healthcare professional if your menopausal symptoms do not improve or get worse on this medicine. Do not change the dose or dosing frequency without talking to your doctor first.

Tell all your healthcare providers you are on estradiol before a minor or major surgery, including dental treatments.

Tell your healthcare professional if you become pregnant while on estradiol.

Estradiol Drug Interactions

Taking estradiol with certain other drugs can affect how the medicines work. Possible interactions between estradiol and other medications can increase the risk of serious adverse events. Your doctor may change the dose of your medications, switch you to another medication, or monitor you carefully for side effects if there are known interactions between estradiol and your other medicines. Estradiol can have drug interactions with the following medications:

Anti-seizure medications such as phenobarbital and carbamazepine

Anti-tubercular drugs like rifampin

Antibiotics such as erythromycin and clarithromycin

Antifungal agents such as ketoconazole and itraconazole

HIV medications such as ritonavir

Herbal remedies such as St. John’s Wort (Hypericum perforatum)

The above list may not include all the possible drug interactions of estradiol. Give your healthcare professional a complete list of all the medications you are taking, including prescription drugs, non-prescription medicines, dietary supplements, and herbal remedies. Also, tell your healthcare provider if you smoke, drink alcohol, or use recreational drugs because some of these substances can cause serious health complications when used with prescription and over-the-counter medicines.

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