Drug Detail:Estradiol (injection) (Estradiol (injection) [ ess-tra-dye-ol ])
Drug Class: Estrogens
Usual Adult Dose for Postmenopausal Symptoms
ORAL:
Initial dose: 0.5 to 2 mg orally once a day
- Adjust dose as necessary to control symptoms
TRANSDERMAL:
Extended-release (ER) Transdermal Film:
TWICE-weekly (Vivelle-dot, Minivelle, Alora, Dotti, Lyllana): Initial dose: 0.0375 to 0.05 mg/24 hours applied topically twice a week
- Adjust dose based on clinical response
ONCE-weekly (Climara): Initial dose: 0.025 mg/24 hours applied topically once a week
- Adjust dose based on clinical response
Transdermal 0.1% Gel Packets (Divigel):
Initial dose: Apply 0.25 mg topically once a day to the skin of either the right or left upper thigh
- Adjust the dose as needed (packets available as estradiol 0.25, 0.5, 0.75, 1, and 1.25 mg)
Transdermal Metered-Dose Pump
Initial dose (Elestrin): Apply 1 pump (0.52 mg) topically to upper arm once a day; dose adjustments can be made based on clinical response
Initial dose (Estrogel): Apply 1 pump (0.75 mg) topically once a day to arm; dose adjustments can be made based on clinical response
Transdermal Spray: (Evamist; 1 spray delivers 1.53 mg of estradiol):
Initial dose: 1 spray once a day in the morning to the forearm
- Adjust dose based on clinical response
VAGINAL:
Vaginal ring (Femring): 1 ring intravaginally once every 3 months
- Therapy should generally be initiated with 0.05 mg estradiol/day; adjust dose based on clinical response; a second strength delivering estradiol 0.1 mg/day is available
PARENTERAL:
- estradiol cypionate (Depo-estradiol): 1 to 5 mg IM every 3 to 4 weeks
- estradiol valerate (Delestrogen): 10 to 20 mg IM every 4 weeks
Comments:
- When estrogen is prescribed for a postmenopausal woman with a uterus, a progestogen should be co-prescribed to reduce the risk of endometrial cancer; some hysterectomized women with a history of endometriosis may need a progestogen (i.e., residual endometrial implants post hysterectomy).
- See Other Comments/Administration Advice for administration instructions.
- Estrogen should be used at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman; reevaluate periodically as clinically appropriate to determine whether treatment is still necessary.
Uses: For the treatment of moderate to severe vasomotor symptoms associated with menopause.
Usual Adult Dose for Atrophic Urethritis
VAGINAL:
Vaginal cream (Estrace): Initial dose: 2 to 4 g intravaginally once a day for 1 or 2 weeks, then gradually reduce dose by half (goal to restore vaginal mucosa)
- Maintenance dose: 1 g intravaginally 1 to 3 times a week
Vaginal inserts (Vagifem): 10 mcg intravaginally once a day for 2 weeks
- Maintenance dose: 10 mcg intravaginally twice a week
Vaginal ring (Femring, Estring): 1 ring intravaginally once every 3 months
- Therapy should generally be initiated at 0.0075 mg/day or 0.05 mg estradiol/day; adjust dose based on clinical response; a 0.1 mg/day vaginal ring is also available
TRANSDERMAL:
Extended-release (ER) Transdermal Film:
TWICE-weekly (Vivelle-dot, Alora): Initial dose: 0.0375 mg/24 hours applied topically twice a week
- Adjust dose based on clinical response
ONCE-weekly (Climara): Initial dose: 0.025 mg/24 hours applied topically once a week
- Adjust dose based on clinical response
Transdermal Metered-Dose Pump
Initial dose (Estrogel): Apply 1 pump (0.75 mg) topically once a day to arm; dose adjustments can be made based on clinical response
ORAL:
Initial dose: 0.5 to 2 mg orally once a day
- Adjust dose as necessary to control symptoms
PARENTERAL:
- estradiol cypionate (Depo-estradiol): 1 to 5 mg IM every 3 to 4 weeks
- estradiol valerate (Delestrogen): 10 to 20 mg IM every 4 weeks
Comments:
- When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, first consider topical vaginal products.
- When estrogen is prescribed for a postmenopausal woman with a uterus, a progestogen should be co-prescribed to reduce the risk of endometrial cancer; some hysterectomized women with a history of endometriosis may need a progestogen (i.e., residual endometrial implants post hysterectomy).
- See Other Comments/Administration Advice for administration instructions.
- Use estrogen at the lowest effective dose and the shortest duration consistent with treatment goals and risks for the individual woman; reevaluate periodically as clinically appropriate to determine whether treatment is still necessary.
Use: For the treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with menopause.
Usual Adult Dose for Atrophic Vaginitis
VAGINAL:
Vaginal cream (Estrace): Initial dose: 2 to 4 g intravaginally once a day for 1 or 2 weeks, then gradually reduce dose by half (goal to restore vaginal mucosa)
- Maintenance dose: 1 g intravaginally 1 to 3 times a week
Vaginal inserts (Vagifem): 10 mcg intravaginally once a day for 2 weeks
- Maintenance dose: 10 mcg intravaginally twice a week
Vaginal ring (Femring, Estring): 1 ring intravaginally once every 3 months
- Therapy should generally be initiated at 0.0075 mg/day or 0.05 mg estradiol/day; adjust dose based on clinical response; a 0.1 mg/day vaginal ring is also available
TRANSDERMAL:
Extended-release (ER) Transdermal Film:
TWICE-weekly (Vivelle-dot, Alora): Initial dose: 0.0375 mg/24 hours applied topically twice a week
- Adjust dose based on clinical response
ONCE-weekly (Climara): Initial dose: 0.025 mg/24 hours applied topically once a week
- Adjust dose based on clinical response
Transdermal Metered-Dose Pump
Initial dose (Estrogel): Apply 1 pump (0.75 mg) topically once a day to arm; dose adjustments can be made based on clinical response
ORAL:
Initial dose: 0.5 to 2 mg orally once a day
- Adjust dose as necessary to control symptoms
PARENTERAL:
- estradiol cypionate (Depo-estradiol): 1 to 5 mg IM every 3 to 4 weeks
- estradiol valerate (Delestrogen): 10 to 20 mg IM every 4 weeks
Comments:
- When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, first consider topical vaginal products.
- When estrogen is prescribed for a postmenopausal woman with a uterus, a progestogen should be co-prescribed to reduce the risk of endometrial cancer; some hysterectomized women with a history of endometriosis may need a progestogen (i.e., residual endometrial implants post hysterectomy).
- See Other Comments/Administration Advice for administration instructions.
- Use estrogen at the lowest effective dose and the shortest duration consistent with treatment goals and risks for the individual woman; reevaluate periodically as clinically appropriate to determine whether treatment is still necessary.
Use: For the treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with menopause.
Usual Adult Dose for Hypoestrogenism
ORAL:
Initial dose: 1 to 2 mg orally once a day
- Adjust dose to control symptoms
TRANSDERMAL:
Extended-release (ER) Transdermal Film:
TWICE-weekly (Vivelle-dot, Minivelle, Alora): Initial dose: 0.0375 or 0.05 mg/24 hours applied topically twice a week
- Adjust dose based on clinical response
ONCE-weekly (Climara): Initial dose: 0.025 mg/24 hours applied topically once a week
- Adjust dose based on clinical response
PARENTERAL:
- estradiol cypionate (Depo-estradiol): 1.5 to 2 mg IM every 4 weeks
- estradiol valerate (Delestrogen): 10 to 20 mg IM every 4 weeks
Comments:
- Adjust dose as needed to control symptoms; the minimal effective dose for maintenance therapy should be determined by titration.
- See Other Comments/Administration Advice for administration instructions.
Uses: For the treatment of female hypoestrogenism due to hypogonadism, castration, or primary ovarian failure.
Usual Adult Dose for Oophorectomy
ORAL:
Initial dose: 1 to 2 mg orally once a day
- Adjust dose as necessary to control presenting symptoms
PARENTERAL:
- estradiol valerate (Delestrogen): 10 to 20 mg IM every 4 weeks
TRANSDERMAL:
Extended-release (ER) Transdermal Film:
TWICE-weekly (Vivelle-dot, Minivelle, Alora): Initial dose: 0.0375 or 0.05 mg/24 hours applied topically twice a week
- Adjust dose based on clinical response
ONCE-weekly (Climara): Initial dose: 0.025 mg/24 hours applied topically once a week
- Adjust dose based on clinical response
Comments:
- Adjust dose as needed to control symptoms; the minimal effective dose for maintenance therapy should be determined by titration.
- See Other Comments/Administration Advice for administration instructions.
Use: For treatment of female hypoestrogenism due primary ovarian failure.
Usual Adult Dose for Primary Ovarian Failure
ORAL:
Initial dose: 1 to 2 mg orally once a day
- Adjust dose as necessary to control presenting symptoms
PARENTERAL:
- estradiol valerate (Delestrogen): 10 to 20 mg IM every 4 weeks
TRANSDERMAL:
Extended-release (ER) Transdermal Film:
TWICE-weekly (Vivelle-dot, Minivelle, Alora): Initial dose: 0.0375 or 0.05 mg/24 hours applied topically twice a week
- Adjust dose based on clinical response
ONCE-weekly (Climara): Initial dose: 0.025 mg/24 hours applied topically once a week
- Adjust dose based on clinical response
Comments:
- Adjust dose as needed to control symptoms; the minimal effective dose for maintenance therapy should be determined by titration.
- See Other Comments/Administration Advice for administration instructions.
Use: For treatment of female hypoestrogenism due primary ovarian failure.
Usual Adult Dose for Breast Cancer-Palliative
10 mg orally 3 times a day for at least 3 months
Comments:
- As a palliative treatment for breast cancer in appropriately selected women and men with metastatic disease.
Use: For treatment of breast cancer (palliation only).
Usual Adult Dose for Osteoporosis
TRANSDERMAL:
Extended-release (ER) Transdermal Film:
TWICE-weekly (Vivelle-dot, Minivelle, Alora): Initial dose: 0.025 mg/24 hours applied topically twice a week
- Adjust dose as needed
- Adjust dose as needed
ORAL: 0.5 to 2 mg orally once a day
- Use lowest effective dose; however, lowest effective dose has not been definitively determined.
Comments:
- If estrogen is being used solely for postmenopausal osteoporosis prevention, first consider the use of non-estrogen medications; consider estrogen only for women at significant risk of osteoporosis.
- When estrogen is prescribed for a postmenopausal woman with a uterus, a progestogen should be co-prescribed to reduce the risk of endometrial cancer; some hysterectomized women with a history of endometriosis may need a progestogen (i.e., residual endometrial implants post hysterectomy).
- See Other Comments/Administration Advice for administration instructions.
- Use estrogen at the lowest effective dose and the shortest duration consistent with treatment goals and risks for the individual woman; reevaluate periodically as clinically appropriate to determine whether treatment is still necessary.
Use: For the treatment of osteoporosis.
Usual Adult Dose for Prostate Cancer
ORAL: 1 to 2 mg orally 3 times a day
PARENTERAL:
estradiol valerate (Delestrogen): 30 mg or more IM every 1 to 2 weeks
Use: For the treatment (palliation only) of advanced androgen-dependent prostate carcinoma
Usual Adult Dose for Dyspareunia
Vaginal Insert:
Initial dose: 1 insert (4 mcg) intravaginally once a day for 2 weeks
Maintenance dose: 1 insert (4 or 10 mcg) intravaginally twice a week
Comments:
- Dose adjustment should be guided by clinical response. Women should generally start with the 4 mcg dose.
- When estrogen is prescribed for a postmenopausal woman with a uterus, a progestogen should be co-prescribed to reduce the risk of endometrial cancer; some hysterectomized women with a history of endometriosis may need a progestogen (i.e., residual endometrial implants post hysterectomy).
- See Other Comments/Administration Advice for administration instructions.
- Use estrogen at the lowest effective dose and the shortest duration consistent with treatment goals and risks for the individual woman; reevaluate periodically as clinically appropriate to determine whether treatment is still necessary.
Use: For the treatment of moderate to severe dyspareunia, a symptoms of vulvar and vaginal atrophy due to menopause.
Renal Dose Adjustments
Use caution; estrogens may cause some degree of fluid retention
Liver Dose Adjustments
Contraindicated in patients with hepatic impairment or disease
Precautions
US BOXED WARNINGS: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, and BREAST CANCER - Prescribe estrogens, with or without progestogens, at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman:
- Estrogen Alone Therapy:
- ENDOMETRIAL CANCER: There is an increased risk of endometrial cancer in woman with a uterus using unopposed estrogens; adding a progestin has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Diagnostic measures, including directed or random endometrial sampling should be performed when indicated, to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.
- CARDIOVASCULAR DISORDERS and PROBABLE DEMENTIA: Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia. The Women's Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years) taking conjugated estrogen (CE; 0.625 mg/day) for 7.1 years, relative to placebo. The WHI-Memory Study (WHIMS) substudy reported an increased risk of developing probable dementia in postmenopausal women over 65 years taking CE (0.625 mg/day) for 5.2 years, relative to placebo; it is unknown if this applies to younger postmenopausal women. The only estrogen in the WHI studies was CE 0.625 mg/day. The relevance of findings to lower doses, other routes of administration, or other estrogen-alone products is unknown. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks to other products. Discuss the benefits and risks of estrogen-alone therapy with patients, taking into account their individual risk profiles.
- Estrogen Plus Progestin Therapy:
- CARDIOVASCULAR DISORDERS and PROBABLE DEMENTIA: Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia. The WHI estrogen plus progestin substudy reported increased risks of stroke, DVT, pulmonary embolism (PE), and myocardial infarction (MI) in postmenopausal women (50 to 79 years) taking daily CE 0.625 mg plus medroxyprogesterone (MPA; 2.5 mg) for 5.6 years, relative to placebo. The WHIMS estrogen plus progestin substudy reported an increased risk of developing probable dementia in postmenopausal women over 65 years taking daily CE 0.625 mg plus MPA 2.5 mg for 4 years, relative to placebo; it is unknown if this applies to younger postmenopausal women.
- BREAST CANCER: The WHI estrogen plus progestin substudy reported an increased risk of invasive breast cancer. The only estrogen-progestogen studied was once daily CE 0.625 mg plus MPA 2.5 mg and therefore, the relevance of these findings regarding adverse cardiovascular events, dementia and breast cancer to lower CE plus other MPA doses, other routes of administration, or other estrogen plus progestogen products is unknown. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss the benefits and risks of estrogen plus progestogen therapy with patients, taking into account their individual risk profiles.
CONTRAINDICATIONS:
- Undiagnosed abnormal genital bleeding
- Breast cancer, or history of breast cancer
- Estrogen dependent neoplasia
- Active, or a history of DVT or PE
- Active, or history of arterial thromboembolic disease (e.g. stroke or MI)
- Anaphylactic reaction or angioedema, or hypersensitivity to active substance or any of the product ingredients
- Hepatic impairment or disease
- Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders
- Pregnancy
Safety and efficacy have not been established in patients younger than 18 years.
Consult WARNINGS section for additional precautions.
Dialysis
Use caution; dose reduction may be advisable in women with ESRD receiving hemodialysis
Other Comments
Administration advice:
- Due to number of different products, the manufacturer's product labeling should be consulted for brand specific administration instructions and storage; illustrations are often provided for further guidance
PARENTERAL: IM administration only
- Delestrogen: Administer IM only into upper, outer quadrant of the gluteal muscle
TRANSDERMAL: Apply to clean, dry, unbroken skin; wash hands after application; do not apply to breasts
- Patches: Apply to clean, dry area of the lower abdomen (below the umbilicus) or upper quadrant of the buttock
- Estrogel: Prime canister before first use (depress pump 3 times); apply a thin layer over the entire arm on the inside and outside from wrist to shoulder
- Elestrin: Prime pump before first use; apply onto skin in a thin layer; the recommended area of application is the upper arm to shoulder; allow gel to dry for at least 5 minutes before dressing; do not apply sunscreen to area for at least 25 minutes
- Divigel: Apply entire contents of unit dose packet to skin of either the right or left upper thigh; application surface area should be about 5 by 7 inches; allow to dry before dressing, do not wash site within 1 hour
- Evamist: Pump should be primed by spraying 3 sprays with the cover on; the container should be held upright and vertical for spraying; sprays are applied to adjacent, non-overlapping areas on the inner surface of the forearm, starting near the elbow; allow to dry for approximately 2 minutes before dressing; the site should not be washed for at least 1 hour
VAGINAL:
Vaginal Cream: Gently squeeze tube from bottom to expel the prescribed amount into the applicator; insert applicator deeply into vagina and press plunger downward
Vaginal Insert:
- Imvexxy: Insert with smaller end up for a depth of about 2 inches into the vaginal canal
- Estring, Femring: Insert as deeply as possible into the upper one-third of the vaginal vault; allow to remain in place for 3 months, then remove and replace with a new ring
Storage requirements:
- Consult manufacturer's product information
General:
- For women with an intact uterus, studies have shown the addition of progestin for 10 or more days of an estrogen cycle, or daily with estrogen in a continuous regimen, result in a lower incidence of endometrial hyperplasia than estrogen alone. Endometrial hyperplasia may be a precursor to endometrial cancer.
- There are possible risks associated with use of progestins and these risks should be considered.
- Estrogen therapy should be guided by goals of therapy and clinical response; the lowest effective dose should be used for the shortest duration consistent with treatment goals and risks for the individual woman. Patients should be reevaluated periodically, as clinically appropriate (e.g., 3-month to 6-month intervals) to determine if treatment is still necessary.
Monitoring:
- Monitor thyroid function in women on thyroid replacement
- Women should receive yearly mammography, with increased frequency as needed
Patient advice:
- Patients should be instructed to read the US FDA-approved patient labeling (Patient Information and Instructions for Use).
- Patients should be instructed to report vaginal bleeding to their healthcare provider as soon as possible.
- Patients should discuss with their healthcare provider the possible serious adverse reactions of therapy including cardiovascular disorders, malignant neoplasms, and possible dementia.
- For patients with an intact uterus, they should understand the benefit of concomitant progestin use.
