Estradiol

Estradiol is a female hormone (estrogen). It is used by women to help reduce vaginal symptoms of menopause (such as vaginal dryness/burning/itching). These symptoms are caused by the body making less estrogen. When treating only vaginal symptoms of menopause, products applied directly inside the vagina (such as this medication) should be used first. Estrogens that are taken by mouth, absorbed through the skin, or injected may have greater risks of side effects due to more estrogen being absorbed.

Estradiol is available under the following different brand names: Estrace, Vivelle-Dot, Delestrogen, DepoEstradiol, Divigel, Elestrin, Alora, Estrace Cream, Estraderm Transdermal, estradiol topical, Estradot, Estrasorb, Estrogel, Evamist, Femtrace, Menostar, Minivelle, Vivelle, and Climara.

Dosages of Estradiol:

Dosage Forms and Strengths

Gel

• 0.06%
• 0.1%

Injectable solution

• 5 mg/mL
• 10 mg/mL
• 20 mg/mL
• 40 mg/mL

Tablet

• 0.45 mg (as acetate)
• 0.5 mg
• 0.9 mg (as acetate)
• 1 mg
• 1.5 mg
• 2 mg

Transdermal patch

• 0.0375 mg
• 0.05 mg
• 0.06 mg
• 0.075 mg
• 0.1 mg

Topical emulsion

• 4.35 mg/1.74g (0.25%)

Dosage Considerations – Should be Given as Follows:

• Pediatric: Safety and efficacy not established

Vulvar and Vaginal Atrophy in Menopause

• Estrace: 1-2 mg orally once daily for 3 weeks, followed by 1 week off
• Valerate: 10-20 mg intramuscularly (IM) every 4 weeks
• EstroGel: 1.25 g/day 3 weeks on, 1 week off
• Alora, Climara Vivelle-Dot, Estraderm: Use transdermally and follow product-specific directions
• Prevention of osteoporosis: 0.5 mg orally once daily for 3 weeks, followed by 1 week off
• Metastatic breast cancer: 10 mg orally every 8 hours for 3 months
• Prostate cancer: 1-2 mg orally every 8 hours for 3 months or more

Hypoestrogenism from Castration, Hypogonadonism, or Ovarian Failure

• Oral (Estrace): 1-2 mg orally once/day; titrate to use minimal effective dose
• Transdermal (Alora, Estraderm, Climara, Vivelle-Dot, Minivelle): Use transdermally and follow product-specific directions
• Valerate: 10-20 mg intramuscularly (IM) every 4 weeks

Hypoestrogenism

• Cypionate: 1.5-2 mg intramuscularly (IM) every 4 weeks

Osteoporosis

• Oral (Estrace): 0.5 mg/day for 23 days of 28-day cycle used in clinical studies
• Transdermal (Alora, Menostar, Estraderm, Vivell-Dot, Minivelle): Follow product specific directions

Vasomotor Symptoms Associated with Menopause

• Estrace: 1-2 mg/day 3 weeks on, 1 week off
• Valerate: 10-20 mg intramuscularly (IM) every 3-4 weeks
• Cypionate: 1-5 mg IM every 3-4 weeks
• Estrasorb: 3.48 g of emulsion applied once/day in the morning
• Elestrin: 0.87 g/day gel applied at the same time each day; use patient's response to adjust dose
• Divigel: 0.25 g/day gel; adjust dose based on patient response
• EstroGel: 1.25 g/day gel applied at the same time each day

Prostate Cancer

• Estrace: 1-2 mg orally three times daily
• Valerate: 30 mg intramuscularly (IM) or more every 1-2 weeks

Side effects associated with use of Estradiol, include the following:

• Abdominal cramping
• Anxiety
• Bloating
• Breakthrough bleeding
• Breast enlargement
• Breast tenderness/pain/swelling
• Freckles or darkening of facial skin (melasma)
• Changes in menstrual periods
• Delayed ejaculation
• Depression
• Dry mouth
• Excessive thirst
• Fainting or lightheadedness
• Headache
• High blood pressure (hypertension)
• Impotence
• Influenza
• Itching
• Loss of scalp hair
• Missed menstrual periods
• Muscle cramps
• Nausea
• Nervousness
• Rash
• Skin irritation and redness at application site (transdermal)
• Spotting
• Stomach cramps
• Stomach upset
• Swelling
• Swelling of extremities
• Toothache
• Vaginal discharge
• Vaginal discomfort, vaginal erosion, vaginal ulceration, adherence of the vaginal ring to the vaginal wall (Estring)
• Vomiting
• Weight changes

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

Severe Interactions of estradiol include:

• ospemifene

Estradiol has serious interactions with at least 32 different drugs.

Estradiol has moderate interactions with at least 185 different drugs.

Estradiol has mild interactions with at least 34 different drugs.

This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns or for more information about this medicine.

Warnings

• Increased risk of endometrial cancer
• Close clinical surveillance of all women taking estrogens is important
• Risk of endometrial cancer increases with use of unopposed estrogens; adding progestin to estrogen therapy may reduce risk of endometrial hyperplasia, a precursor to endometrial cancer;
• Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding
• Cardiovascular risks
• Estrogens with and without progestins should not be used to prevent cardiovascular disease
• Estrogens plus progestins: Women's Health Initiative (WHI) Estrogen Plus Progestin sub-study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary embolism (PE), and deep vein thrombosis (DVT) in postmenopausal women (50-79 years) during 5.6 years of treatment with daily PO conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) in comparison with placebo
• Estrogens alone: Sub-study of WHI study reported increased risk of stroke and DVT in postmenopausal women (50-79 years) during 6.8 years of treatment with PO conjugated estrogens (0.625 mg/day) alone in comparison with placebo
• Dementia risks
• Estrogens with and without progestins should not be used to prevent dementia
• Women's Health Initiative Memory Study (WHIMS), sub-study of WHI study, reported increased risk of developing probable dementia in postmenopausal women 65 years and older during 4 years of treatment with daily PO conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) in comparison with placebo
• Estrogens alone: Sub-study of WHIMS reported increased risk of developing probable dementia in postmenopausal women 65 years and older during 5.2 years of treatment with conjugated estrogens (0.625 mg/day) alone in comparison with placebo
• Unknown whether these findings apply to younger postmenopausal women
• Breast cancer
• The Women's Health Initiative (WHI) estrogen plus progestin sub-study also demonstrated an increased risk of invasive breast cancer; estrogens with or without progestins should be prescribed at the lowest doses and for the shortest duration
• Dose and duration
• In the absence of comparable data, these risks should be assumed to be similar for other doses of conjugated estrogens and medroxyprogesterone acetate, as well as for other combinations and dosage forms of estrogens and progestins
• Because of these risks, estrogens with or without progestins should be prescribed at lowest effective dose and for shortest duration consistent with treatment goals and individual risks
• Unintentional secondary exposure to transdermal products
• Breast budding, breast masses in prepubertal females, and gynecomastia in prepubertal males have been reported after unintentional secondary exposure

Contraindications

• Documented hypersensitivity
• Known anaphylactic reaction or angioedema with topical emulsion
• Known protein C, protein S, or antithrombin deficiency or other known thrombophilic disorder
• Active or previous breast cancer
• Arterial thromboembolic disease (stroke, myocardial infarction [MI]), thrombophlebitis, deep vein thrombosis/pulmonary embolism (DVT/PE), thrombogenic valvular disease
• Estrogen-dependent neoplasia
• Uncontrolled hypertension, diabetes mellitus with vascular involvement, jaundice with previous oral contraceptive (OC) use
• Undiagnosed abnormal vaginal bleeding
• Liver disease, liver tumors

Effects of Drug Abuse

• No information provided

Short-Term Effects

• See "What Are Side Effects Associated with Using Estradiol?"

Long-Term Effects

• Increased risk of oral contraceptive (OC) use; however human papillomavirus (HPV) remains main risk factor for this cancer; evidence suggests long-term (5 years or more) use of OCs may be associated with increased risk.
• Increased risk of liver cancer with OC use; risk increases with longer duration of use
• An increased risk of invasive breast cancer reported with estrogen plus progestin in WHI sub-study; estrogens with or without progestins should be prescribed at lowest doses and for shortest duration
• See "What Are Side Effects Associated with Using Estradiol?"

Cautions

• Severe anaphylactic reactions including hives, itching, swollen lips-tong-face, respiratory compromise, abdominal pain, vomiting during transdermal treatment reported
• Family history of breast cancer or DVT/PE; current or previous depression, endometriosis, diabetes mellitus, hypertension, bone mineral density changes, renal or hepatic impairment, bone metabolic disease, systemic lupus erythematosus; conditions exacerbated by fluid retention (e.g., migraine, asthma, epilepsy)
• Discontinue if the following develop: yellow skin or eyes (jaundice), visual problems (may cause contact lens intolerance), any signs of venous thromboembolism, migraine with unusual severity, significant blood pressure increase, severe depression, increased risk of thromboembolic complications after surgery
• Discontinue 4 weeks before major surgery or prolonged immobilization
• Patients on warfarin or other oral anticoagulants (increase in anticoagulant dose may be warranted)
• Some studies link oral contraceptive (OC) use with increased risk of breast cancer, whereas other studies have not shown any change in risk; risk depends on conditions where naturally high hormone levels persist for long periods, including early-onset menstruation (less than 12 years), late-onset menopause (over 55 years), first child after age 30 years, nulliparity
• Increased risk of oral contraceptive (OC) use; however human papillomavirus (HPV) remains main risk factor for this cancer; evidence suggests long-term (5 years or more) use of OCs may be associated with increased risk
• Increased risk of liver cancer with OC use; risk increases with longer duration of use
• Hypercalcemia may occur in patients with breast cancer or bone metastases
• Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema
• Angioedema involving eye/eyelid, face, larynx, pharynx, tongue and extremity (hands, legs, ankles, and fingers) with or without hoves reported; discontinue therapy permanently if angioedema occurs
• Femring is more potent than Estring and should be used with progesterone therapy to prevent endometrial hyperplasia
• Caution regarding unintentional exposure in children
• Risk of endometrial cancer increases with use of unopposed estrogens
• An increased risk of invasive breast cancer reported with estrogen plus progestin in Women's Health Initiative (WHI) sub-study; estrogens with or without progestins should be prescribed at lowest doses and for shortest duration
• There is no evidence that the use of "natural" estrogens results in different endometrial risk profile from use of synthetic estrogens at equivalent estrogen doses

Pregnancy and Lactation

• Do not use estradiol in pregnancy
• The risks involved outweigh potential benefits
• Safer alternatives exist
• Estradiol enters breast milk; use with caution if breastfeeding