Estradiol

• Estradiol is used for symptomatic relief of menopausal symptoms such as hot flushes and vaginal dryness, itching, or burning.
• Estradiol may help prevent osteoporosis in women with estrogen deficiency from natural or surgical menopause, when combined with adequate diet, calcium and vitamin D intake, smoking cessation, and weight-bearing exercise.
• In women who still have a uterus, estradiol should always be combined with a progestin given on a cyclic schedule to reduce the risk of overgrowth of the uterine lining.

Contraindicated in pregnancy. Confirm pregnancy status and discuss alternative therapy with the prescriber before dispensing.

• Estradiol is contraindicated in known or suspected pregnancy; estrogens are not indicated for use during pregnancy.

• Estradiol is contraindicated during breastfeeding.

• Use of combined estrogen plus progestin therapy in women aged 65 and older may increase the risk of developing probable dementia.
• Evidence suggests use in the geriatric population may be associated with differences in safety or effectiveness compared with younger patients.

• Estradiol has not been studied in patients under 18 years of age, and no pediatric indication has been authorized.

• For menopausal symptoms, treatment is usually started with 1 mg once daily, adjusted afterward to the individual's needs; tapering or stopping should be attempted at 3- to 6-month intervals.
• For prevention of osteoporosis, treatment is usually started with 0.5 mg once daily as soon as possible after menopause, and the dose may be adjusted based on clinical response.
• In women who still have a uterus, estrogen is generally given for the first 21 to 25 days of each month, with a progestin added for the last 12 to 14 days of that cycle to protect the uterine lining; women who have had a hysterectomy can take estrogen continuously every day.
• The lowest effective dose should be used, and estradiol should be prescribed at the lowest dose and for the shortest duration appropriate for the condition being treated.
• If a dose is missed, it should be taken as soon as remembered unless it is almost time for the next dose, in which case the missed dose should be skipped; doses should not be doubled.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• Reports of large overdoses of estrogen products, including in young children, have not shown serious acute effects.
• Overdose in women may cause nausea, breast discomfort, fluid retention, bloating, or vaginal bleeding.
• Treatment involves removing unabsorbed drug from the stomach by gastric lavage and providing symptomatic care.

• Nausea may occur.
• Bloating or abdominal cramps may occur.
• Breast pain, tenderness, or swelling may occur.
• Headache may occur.
• Nervousness or irritability may occur.
• Weight or appetite changes may occur.
• Vaginal bleeding, spotting, or discharge may occur.
• Acne may occur.
• Dark patches of facial skin (melasma) may occur.
• Hair loss or abnormal hair growth may occur.
• Fatigue may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Combined estrogen plus progestin therapy increases the risk of heart attack, stroke, invasive breast cancer, and blood clots in the lungs or legs.
• Estrogen-alone therapy increases the risk of stroke and blood clots in the veins.
• Unopposed estrogen in women who still have a uterus increases the risk of overgrowth of the uterine lining and uterine cancer.
• Long-term hormone replacement therapy use of five years or more has been associated with an increased risk of ovarian cancer.
• Combined estrogen plus progestin therapy in women 65 and older may increase the risk of probable dementia.
• The risk of gallbladder disease requiring surgery is increased with estrogen use.
• Blood clots in the eye can cause sudden partial or complete vision loss.
• Liver problems, including jaundice, may occur.
• Pre-existing uterine fibroids may grow larger during estrogen therapy.
• Seek urgent medical attention for chest pain, sudden shortness of breath, leg swelling or pain, sudden vision changes, sudden severe headache, or signs of a stroke.

• Use with caution in women with a personal or family history of breast disease, abnormal mammograms, or breast biopsies.
• Use with caution in women with a history or risk factors for blood clots, including obesity, smoking, or prolonged immobility.
• Use with caution in women with high blood pressure, since estrogen therapy can raise blood pressure further.
• Use with caution in women with diabetes or a predisposition to diabetes, since estrogen can worsen blood sugar and lipid control.
• Use with caution in women with a history of liver or gallbladder disease.
• Use with caution in women with epilepsy, asthma, or kidney disease, since fluid retention from estrogen may worsen these conditions.
• Use with caution in women with high triglycerides or a family history of high blood fats, since estrogen can raise triglyceride levels.
• Use with caution in women with a history of migraine, since estrogen may trigger or worsen migraine episodes.
• Estrogens should be discontinued at least 4 weeks before major surgery associated with an increased risk of blood clots.

• Contraindicated in liver dysfunction or disease until liver function tests return to normal.
• Contraindicated in known or suspected estrogen-dependent cancers, such as endometrial cancer.
• Contraindicated in endometrial hyperplasia.
• Contraindicated in known, suspected, or past history of breast cancer.
• Contraindicated in undiagnosed abnormal genital bleeding.
• Contraindicated in known or suspected pregnancy.
• Contraindicated during breastfeeding.
• Contraindicated in active or past history of blood clots in the arteries, such as stroke, heart attack, or coronary heart disease.
• Contraindicated in classical migraine.
• Contraindicated in active or past history of confirmed venous thromboembolism or active thrombophlebitis.
• Contraindicated in partial or complete vision loss or double vision caused by blood vessel disease in the eye.
• Contraindicated in patients with known hypersensitivity to estradiol or any ingredient in the product.

• Estradiol may reduce the effectiveness of anticoagulants, antidiabetic drugs, and antihypertensive drugs.
• Inducers of the CYP3A4 enzyme, such as St. John's Wort, phenobarbital, carbamazepine, and rifampin, may lower estrogen levels and reduce its effectiveness.
• Inhibitors of CYP3A4, such as erythromycin, clarithromycin, ketoconazole, itraconazole, and ritonavir, may raise estrogen levels and increase the risk of side effects.
• Other liver enzyme-inducing drugs, including barbiturates, hydantoins, meprobamate, and phenylbutazone, may reduce the effect of oral estrogens.
• St. John's Wort and other over-the-counter herbal products may interfere with estrogen metabolism and alter its safety or effectiveness.
• Estradiol can affect the results of certain thyroid and liver function tests, so laboratory staff should be informed that the patient is taking estrogen therapy.

• Estradiol can be taken with or without food, though grapefruit juice may raise estrogen levels and should be used with caution.

• Estradiol tablets are taken once daily at about the same time each day, with or without food.

• Store estradiol tablets at room temperature (15°C to 30°C), in a tightly closed container protected from light.

• Estradiol should be used at the lowest effective dose for the shortest time needed to control symptoms.
• Estrogen therapy is not intended to prevent heart disease or stroke.
• Women who still have a uterus need a progestin added to their regimen to protect against uterine cancer.
• Regular follow-up visits, including breast exams and mammograms, are recommended during treatment.
• Report any unusual vaginal bleeding, breast lumps, or signs of blood clots to a healthcare professional promptly.